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Background: Little is known about the risks and benefits of cannabis use in the context of cancer care. This study characterized the prevalence, reasons for use, and perceived benefits of cannabis and compared symptoms and perceived risks between those who reported past 30-day cannabis use and those who did not., Methods: Adults undergoing cancer treatment at a National Cancer Institute-designated cancer center completed measures of sociodemographic characteristics, cannabis use, use modalities, reasons for use, perceived harms/benefits of use, physical and psychological symptoms, and other substance/medication use. Analyses compared patients who used or did not use cannabis in the past 30 days., Results: Participants (N = 267) were 58 years old on average, primarily female (70%), and predominantly White (88%). Over a quarter of respondents (26%) reported past 30-day cannabis use, and among those, 4.5% screened positive for cannabis use disorder. Participants who used cannabis most often used edibles (65%) or smoked cannabis (51%), and they were younger and more likely to be male, Black, and disabled, and to have lower income and Medicaid insurance than participants who did not use cannabis. Those who used cannabis reported more severe symptoms and perceived cannabis as less harmful than those who did not use cannabis. The most common medical reasons for cannabis use were pain, cancer, sleep problems, anxiety, nausea/vomiting, and poor appetite. Participants reported the greatest cannabis-related symptom relief from sleep problems, nausea/vomiting, headaches, pain, muscle spasms, and anxiety., Conclusions: Patients with cancer who used cannabis perceived benefits for many symptoms, although they showed worse overall symptomatology., Plain Language Summary: Among adults undergoing cancer treatment, 26% reported cannabis use in the past 30 days. Those who used cannabis were more likely to be male and disabled and to have lower income and Medicaid insurance than those who did not use cannabis. Participants most commonly reported using cannabis for pain, cancer, sleep, anxiety, and nausea/vomiting and reported the greatest perceived benefits for sleep, nausea/vomiting, headaches, pain, muscle spasms, and anxiety, yet participants who used cannabis also reported feeling worse physically and psychologically compared to those who did not use cannabis. Participants who used cannabis were more likely to report that cannabis was less risky to their health than alcohol, smoking, and opioids than those who did not use cannabis., (© 2023 American Cancer Society.)

Background: Fosnetupitant (FosNTP), an intravenous neurokinin 1 receptor antagonist, demonstrated a favorable safety profile with a potentially low risk of injection site reactions (ISRs) and promising antiemetic efficacy in patients receiving cisplatin-based highly emetogenic chemotherapy in a previous phase 2 study. We conducted a randomized, double-blind safety study to evaluate the safety profile of FosNTP, including ISRs, in patients receiving doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide (AC/EC) chemotherapy., Methods: Patients scheduled to receive AC/EC were randomized 1:1 to receive 235 mg of FosNTP or 150 mg of fosaprepitant (FosAPR), both in combination with 0.75 mg of intravenous palonosetron and 9.9 mg of dexamethasone on day 1. The stratification factors were age category (<55 vs ≥55 years) and study site. The primary end point was the incidence of treatment-related adverse events (TRAEs) with FosNTP., Results: Overall, 102 patients were randomized to FosNTP (n = 52) or FosAPR (n = 50), and all were treated with the study drug and evaluated for safety. The primary end point, the incidence of TRAEs, was similar with FosNTP (21.2%; 95% confidence interval [CI], 11.1%-34.7%) and FosAPR (22.0%; 95% CI, 11.5%-36.0%), with any-cause ISRs observed in 5.8% and 26.0% of patients, respectively, and treatment-related ISRs observed in 0% and 10.0%, respectively. The overall (0-120 hour) complete response (defined as no emetic event and no rescue medication) rate, standardized by age category in the full analysis set, was 45.9% (23 of 51 patients) with FosNTP and 51.3% (25 of 49 patients) with FosAPR., Conclusions: FosNTP demonstrated a favorable safety profile with a very low risk of ISRs in the AC/EC setting., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Uncontrolled chemotherapy-induced nausea and vomiting can reduce patients' quality of life and may result in premature discontinuation of chemotherapy. Although nausea and vomiting are commonly grouped together, research has shown that antiemetics are clinically effective against chemotherapy-induced vomiting (CIV) but less so against chemotherapy-induced nausea (CIN). Nausea remains a problem for up to 68% of patients who are prescribed guideline-consistent antiemetics. Despite the high prevalence of CIN, relatively little is known regarding its etiology independent of CIV. This review summarizes a metagenomics approach to the study and treatment of CIN with the goal of encouraging future research. Metagenomics focuses on genetic risk factors and encompasses both human (ie, host) and gut microbial genetic variation. Little work to date has focused on metagenomics as a putative biological mechanism of CIN. Metagenomics has the potential to be a powerful tool in advancing scientific understanding of CIN by identifying new biological pathways and intervention targets. The investigation of metagenomics in the context of well-established demographic, clinical, and patient-reported risk factors may help to identify patients at risk and facilitate the prevention and management of CIN., (© 2021 American Cancer Society.)

Background: The goal of this study was to characterize cannabis use among patients with breast cancer, including their reasons for and timing of use, their sources of cannabis information and products, their satisfaction with the information found, their perceptions of its safety, and their dialogue about cannabis with their physicians., Methods: United States-based members of the Breastcancer.org and Healthline.com communities with a self-reported diagnosis of breast cancer within 5 years (age ≥ 18 years) were invited to participate in an anonymous online survey. After informed consent was obtained, nonidentifiable data were collected and analyzed., Results: Of all participants (n = 612), 42% (n = 257) reported using cannabis for relief of symptoms, which included pain (78%), insomnia (70%), anxiety (57%), stress (51%), and nausea/vomiting (46%). Furthermore, 49% of cannabis users believed that medical cannabis could be used to treat cancer itself. Of those taking cannabis, 79% had used it during treatment, which included systemic therapies, radiation, and surgery. At the same time, few (39%) had discussed it with any of their physicians., Conclusions: A significant percentage of survey participants (42%) used cannabis to address symptoms; approximately half of these participants believed that cannabis could treat cancer itself. Most participants used cannabis during active cancer treatment despite the potential for an adverse event during this vulnerable time. Furthermore, most participants believed that cannabis was safe and were unaware that product quality varied widely and depended on the source. This study reviews the research on medicinal cannabis in the setting of these findings to help physicians to recognize its risks and benefits for patients with cancer., Lay Summary: Almost half of patients with breast cancer use cannabis, most commonly during active treatment to manage common symptoms and side effects: pain, anxiety, insomnia, and nausea. However, most patients do not discuss cannabis use with their physicians. Instead, the internet and family/friends are the most common sources of cannabis information. Furthermore, most participants believe that cannabis products are safe and are unaware that the safety of many products is untested., (© 2021 American Cancer Society.)

Background: The 5-year overall survival (OS) rate remains at 50% for patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC), thereby underscoring the need for improved treatments. An antidiabetic agent, metformin, was found in retrospective studies to improve survival in patients with HNSCC. Therefore, the authors conducted a phase 1 dose escalation study combining metformin with chemoradiotherapy in patients with LAHNSCC., Methods: Nondiabetic patients with LAHNSCC were enrolled in the current study to receive escalating doses of metformin and CRT based on the modified toxicity probability interval design. Metformin cohort doses included 2000 mg, 2550 mg, and 3000 mg daily in divided doses in addition to cisplatin (at a dose of 100 mg/m 2 on days 1, 22, and 43) and standard radiotherapy (70 grays). Adverse events were categorized as per the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03)., Results: Twenty patients were enrolled, 2 of whom withdrew consent. The median age of the patients was 56 years and the majority were male (83%), were white (88%), had p16-positive disease (72%), and were tobacco users (61%). The median length of metformin exposure was 28.5 days. The most common grade ≥3 toxicities were nausea (11%), vomiting (11%), mucositis (6%), acute kidney injury (17%), anemia (6%), and leukopenia (11%). Dose-limiting toxicities included diarrhea and acute kidney injury. After a median follow-up of 19 months, the 2-year overall survival and progression-free survival rates were 90% and 84%, respectively. No hypoglycemia events or lactic acidosis were observed. Cisplatin administration did not appear to affect metformin pharmacokinetics. The maximum tolerated dose for metformin could not be determined given the limited number of patients who tolerated metformin during chemoradiotherapy., Conclusions: To the authors' knowledge, the current study is the first phase 1 trial combining metformin with chemoradiotherapy. Rates of overall survival and progression-free survival were encouraging in this limited patient population, and warrant further investigation in a phase 2 trial., (© 2019 American Cancer Society.)

Background: Epigenetic abnormalities are manifold in all solid tumors and include changes in chromatin configuration and DNA methylation. The authors designed a phase 1 study to evaluate the oral DNA methyltransferase inhibitor CC-486 combined with the histone deacetylase inhibitor romidepsin in advanced solid tumors with dose expansion to further evaluate pharmacodynamics and possible clinical benefit of the recommended phase 2 dose (RP2D)., Methods: This was a phase 1 study with a 3 + 3 dose-escalation design and an expansion phase for patients with virally mediated cancers. The disease control rate (DCR) was the primary outcome for the expansion cohort. Correlative studies included long interspersed nucleotide element 1 (LINE-1) methylation and drug exposure in blood samples (clinicaltrials.gov identifier NCT01537744)., Results: Fourteen patients were enrolled in the dose-escalation portion at 3 dose levels. Three patients experienced dose-limiting toxicities; the RP2D was oral CC-486 300 mg daily on days 1 through 14 and romidepsin 8 mg/m 2 on days 8 and 15. Because of slow accrual into the expansion phase, the trial was closed after 4 patients enrolled. Common toxicities of the combination included nausea (83.3%), anorexia (72.2%), fatigue (61.1%), and constipation (55.6%). There were 12 patients evaluable for response, 5 with stable disease, of whom 2 received >4 cycles; there were no responses. Exposure to CC-486 and romidepsin was consistent with prior data. LINE-1 methylation on C1D8 was significantly reduced (mean, -6.23; 95% CI, -12.23, -0.24; P = .04)., Conclusions: Although, at the RP2D, the combination of CC-486 and romidepsin was tolerable, no significant anticancer activity was observed. Significant demethylation in post-treatment circulating tumor DNA and biopsies provided proof of target acquisition., (© 2019 American Cancer Society.)

Background: Older patients with advanced cancer who are 100% certain they will be cured pose unique challenges for clinical decision making, but to the authors' knowledge, the prevalence and correlates of absolute certainty about curability (ACC) are unknown., Methods: Cross-sectional data were collected in a geriatric assessment trial. ACC was assessed by asking patients, "What do you believe are the chances that your cancer will go away and never come back with treatment?" Response options were 100% (coded as ACC), >50%, 50/50, <50%, 0%, and uncertain. The willingness to bear adversity in exchange for longevity was assessed by asking patients to consider trade-offs between survival and 2 clinical outcomes that varied in abstractness: 1) maintaining quality of life (QOL; an abstract outcome); and 2) specific treatment-related toxicities (eg, nausea/vomiting, worsening memory). Logistic regression was used to assess the independent associations between willingness to bear adversity and ACC., Results: Of the 524 patients aged 70 to 96 years, approximately 5.3% reported that there was a 100% chance that their cancer would be cured (ACC). ACC was not found to be significantly associated with willingness to bear treatment-related toxicities, but was more common among patients who were willing to trade QOL for survival (adjusted odds ratio, 4.08; 95% CI, 1.17-14.26)., Conclusions: Patients who were more willing to bear adversity in the form of an abstract state, namely decreased QOL, were more likely to demonstrate ACC. Although conversations regarding prognosis should be conducted with all patients, those who are willing to trade QOL for survival may especially benefit from conversations that focus on values and emotions., (© 2019 American Cancer Society.)

Background: Chemotherapy-induced nausea and vomiting remain common, distressing side effects of chemotherapy. It has been reported that acupressure prevents chemotherapy-induced nausea in adults, but it has not been well studied in children., Methods: In this multicenter, prospective, randomized, single-blind, sham-controlled trial, the authors compared acute-phase nausea severity in patients ages 4 to 18 years who were receiving highly emetic chemotherapy using standard antiemetic agents combined with acupressure wrist bands, the most common type of acupressure, versus sham bands. Patients wore acupressure or sham bands continuously on each day of chemotherapy and for up to 7 days afterward. Chemotherapy-induced nausea severity in the delayed phase and chemotherapy-induced vomiting control in the acute and delayed phases also were compared., Results: Of the 187 patients randomized, 165 contributed nausea severity assessments during the acute phase. Acupressure bands did not reduce the severity of chemotherapy-induced nausea in the acute phase (odds ratio [OR], 1.33; 95% confidence limits, 0.89-2.00, in which an OR <1.00 favored acupressure) or in the delayed phase (OR, 1.23; 95% CL, 0.75-2.01). Furthermore, acupressure bands did not improve daily vomiting control during the acute phase (OR, 1.57; 95% CL, 0.95-2.59) or the delayed phase (OR, 0.84; 95% CL, 0.45-1.58). No serious adverse events were reported., Conclusions: Acupressure bands were safe but did not improve chemotherapy-induced nausea or vomiting in pediatric patients who were receiving highly emetic chemotherapy. Cancer 2018;124:1188-96. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: This prospective study describes the procedure-related anxiety, treatment-related anxiety, pain, and nausea experienced by children with standard-risk acute lymphoblastic leukemia (ALL) during the first year of treatment., Methods: This study was undertaken at 31 Children's Oncology Group (COG) sites. Eligible children who were 2 to 9.99 years old were enrolled in a COG trial for patients with newly diagnosed standard-risk ALL from 2005 to 2009. Parents completed a demographic survey at the baseline and the Pediatric Quality of Life Inventory 3.0 Cancer Module (proxy version) and the General Functioning Scale of the Family Assessment Device 1, 6, and 12 months after the diagnosis. The association between patient-related (age, sex, ethnicity, and treatment), parent-related (marital status and education), and family-related factors (functioning, income, and size) and symptom scores was evaluated., Results: The mean scores for procedure-related anxiety, treatment-related anxiety, and pain improved during the first year of treatment (P < .0389). The mean nausea score was poorer 6 months after the diagnosis in comparison with the other assessments (P = .0085). A younger age at diagnosis was associated with significantly worse procedure-related anxiety (P = .004). An older age (P = .0002) and assignment to the intensified consolidation study arm (P = .02) were associated with significantly worse nausea., Conclusions: Children with ALL experienced decreasing treatment-related anxiety, procedure-related anxiety, and pain during the first year of treatment. In comparison with scores at 1 and 12 months, nausea was worse 6 months after the diagnosis. Minimization of procedure-related anxiety in younger children and improved nausea control in older children and those receiving more intensified treatment should be prioritized., Competing Interests: DISCLOSURES The authors made no disclosures., (© 2016 American Cancer Society.)

Background: Cabozantinib inhibits mesenchymal-epithelial transition factor (MET) and vascular endothelial growth factor receptor 2 (VEGFR2) and has demonstrated activity in patients with recurrent glioblastoma, warranting evaluation of the addition of cabozantinib to radiotherapy (RT) and temozolomide (TMZ) for patients with newly diagnosed high-grade glioma., Methods: Cabozantinib doses of 40 mg and 60 mg were explored. Patients on the concurrent treatment arm received cabozantinib daily with standard TMZ and after RT continued cabozantinib daily with adjuvant TMZ. In the maintenance arm, patients who completed RT and ≥1 adjuvant cycle of TMZ continued adjuvant TMZ with added cabozantinib (3 schedules: days 1-28, days 1-14, or days 8-21)., Results: A total of 26 patients (25 with recurrent glioblastoma and 1 patient with anaplastic astrocytoma) aged 30 to 72 years were enrolled (10 to the concurrent arm and 16 to the maintenance arm). The median number of post-RT TMZ cycles was 4.5 (range, 0-14 cycles) in the concurrent arm and 5.5 (range, 1-12 cycles) in the maintenance arm. Cabozantinib at a dose of 60 mg daily was the maximum administered dose and a dose of 40 mg daily was determined to be the maximum tolerated dose for both treatment arms (schedule of days 1-28). The most frequent grade 3/4 adverse events were thrombocytopenia (31% of patients), leukopenia (27% of patients, including 5 patients with neutropenia), and deep vein thrombosis and/or pulmonary embolism (23% of patients) (adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0])., Conclusions: Cabozantinib at a dose of 40 mg daily with RT plus TMZ and post-RT TMZ for patients with newly diagnosed high-grade glioma was generally well tolerated, and demonstrated no pharmacokinetic interactions with concurrent TMZ. Given the strong theoretical rationale for combining anti-VEGF and anti-MET activity with standard therapy, cabozantinib at a dose of 40 mg daily warrants evaluation in combination with standard therapy for patients with newly diagnosed glioblastoma., (© 2015 American Cancer Society.)

Background: The treatment of older adults with acute myeloid leukemia (AML) using standard intensive chemotherapy has been associated with poor outcomes. Effective, less toxic therapies are needed to achieve and maintain durable remissions., Methods: One hundred eighteen patients with newly diagnosed AML (median age, 68 years; range, 60-81 years) were treated with a regimen of clofarabine and low-dose cytarabine (LDAC) alternating with decitabine (DAC). The induction consisted of intravenous clofarabine at 20 mg/m(2) on days 1 to 5 combined with subcutaneous LDAC at 20 mg twice daily on days 1 to 10. Responding patients were then treated with a prolonged consolidation/maintenance regimen consisting of cycles of clofarabine plus LDAC alternating with cycles of DAC., Results: The overall response rate was 68%. The complete remission (CR) rate was 60% overall, 71% for patients with a diploid karyotype, and 50% for patients with an adverse karyotype. The median overall survival (OS) was 11.1 months for all patients and 18.5 months for those achieving a CR/complete remission with incomplete platelet recovery (CRp). The median relapse-free survival for patients achieving a CR/CRp was 14.1 months. According to a multivariate analysis, only adverse cytogenetics and a white blood cell count ≥ 10 × 10(9)/L predicted worse OS. The regimen was well tolerated with 4- and 8-week mortality rates of 3% and 7%, respectively. The most common nonhematologic adverse events were nausea, elevated liver enzymes, and rash., Conclusions: The lower intensity, prolonged-therapy program of clofarabine and LDAC alternating with DAC is well tolerated and highly effective in older patients with AML., (© 2015 American Cancer Society.)

Background: Aldoxorubicin, a prodrug of doxorubicin, covalently binds to serum albumin, allowing for the administration of much higher doses of doxorubicin in a previous clinical study. The current phase 1B/2 study evaluated the safety of aldoxorubicin, including preliminary efficacy and safety of its maximum tolerated dose (MTD)., Methods: Patients aged 18 to 70 years with recurrent/refractory malignant solid tumors received aldoxorubicin at a dose of 230 mg/m(2) , 350 mg/m(2) , or 450 mg/m(2) (170 mg/m(2) , 260 mg/m(2) , or 335 mg/m(2) doxorubicin equivalents, respectively) by intravenous infusion once every 21 days for up to 8 consecutive cycles., Results: A total of 25 patients were enrolled, including 17 patients (68%) with advanced soft tissue sarcoma (STS). The MTD of aldoxorubicin was 350 mg/m(2) ; dose-limiting toxicities included grade 4 neutropenia and grade 3 febrile neutropenia (NCI CTCAE v4.0). Drug-related adverse events included myelosuppression, nausea, fatigue, alopecia, stomatitis, vomiting, and oropharyngeal pain. No clinically significant cardiac toxicities were reported. Seven patients (28%) had elevated serum troponin levels while taking part in the study, but these elevations were not clinically significant or associated with cardiac findings. A partial response was achieved in 20% of patients, and stable disease was reported in 40% of patients. The median progression-free survival was 4.80 months, and the median overall survival was 11.25 months. Among patients with STS who were treated at the MTD (13 patients), a partial response was achieved in 38% and stable disease in 46%; the median progression-free survival was 11.25 months and the median overall survival was 21.71 months., Conclusions: Aldoxorubicin at a dose of 350 mg/m(2) administered once every 21 days for up to 8 cycles was found to be acceptably safe and demonstrated preliminary efficacy in patients with advanced solid tumors, including STS. Further investigation of aldoxorubicin is ongoing., (© 2014 The Authors. American Cancer Society.)

Background: Greater than 70% of patients with cancer experience chemotherapy-induced nausea and vomiting. In the current study, the authors examined the effects of electrostimulation of the K1 acupoint located on the sole of the foot because it is believed to have the potential to control chemotherapy-induced nausea and vomiting., Methods: In this trial, 103 patients diagnosed with primary or metastatic liver cancer were recruited before transcatheter arterial infusion (TAI) of cisplatin or oxaliplatin and randomized to either group A (51 patients who were treated with the antiemetic tropisetron and acustimulation at the K1 acupoint for 20 minutes approximately 1 to 2 hours before TAI on the first day and then daily for the subsequent 5 days) or group B (52 patients who were treated with tropisetron and electrostimulation at a placebo point on the heel). The rate, intensity, and duration of nausea and vomiting were collected at baseline and then daily for 5 days after TAI. Quality of life was assessed daily using the MD Anderson Symptom Inventory and the EuroQoL scale., Results: No differences were found between groups A and B with regard to the incidence and degree of nausea or vomiting on day 1 or the following 5 days. Patients in group A had better EuroQoL scores compared with patients in group B (72.83 in group A vs 65.94 in group B; P =.04) on day 4 but not on the other days. No group differences were noted at any time point for MD Anderson Symptom Inventory scores., Conclusions: Electrostimulation of K1 combined with antiemetics did not result in initial prevention of cisplatin-induced or oxaliplatin-induced nausea or vomiting., (© 2014 American Cancer Society.)

Background: The objective of this study was to elucidate relative preferences of women with ovarian cancer for symptoms, treatment-related side effects, and progression-free survival (PFS) relevant to choosing a treatment regimen., Methods: Women with advanced or recurrent ovarian cancer participated in a survey that included 3 methods to measure patient preferences (ratings, rankings, and a discrete-choice experiment) for 7 attributes: mode of administration, visit frequency, peripheral neuropathy, nausea and vomiting, fatigue, abdominal discomfort, and PFS. Participants were asked to choose between 2 unlabeled treatment scenarios that were characterized using the 7 attributes. Each participant completed 12 choice questions in which attribute levels were assigned according to an experimental design and a fixed-choice question representing 2 chemotherapy regimens for ovarian cancer., Results: In total, 95 women completed the survey. Participants' ratings and rankings revealed greater concern and importance for PFS than for any other attribute (P < .0001 for all). The discrete-choice experiment revealed that the relative odds that a participant would choose a scenario with 18 months, 21 months, and 24 months of PFS versus 15 months of PFS were 1.5 (P = .01), 3.4 (P < .001), and 7.5 (P < .001), respectively. However, participants' choices indicated that they were willing to accept a shorter PFS to avoid severe side effects: 6.7 months to reduce nausea and vomiting from severe to mild, 5.0 months to reduce neuropathy from severe to mild, and 3.7 months to reduce abdominal symptoms from severe to moderate., Conclusions: PFS is the predominant driver of patient preferences for chemotherapy regimens. However, women in the current study were willing to trade significant PFS time for reductions in treatment-related toxicity., (© 2014 American Cancer Society.)

Background: Despite targeted antiemetics, data support an unmet need related to the management of delayed nausea and vomiting (NV). Promising pilot data informed this phase III trial evaluating gabapentin for delayed NV from highly emetogenic chemotherapy (HEC)., Methods: Participants were randomized to receive prophylactic treatment with 20 mg of dexamethasone and a 5HT3 receptor antagonist (RA) on the day of chemotherapy, followed by gabapentin 300 mg twice a day and dexamethasone (dex) or placebo and dex after HEC. Gabapentin/placebo was started the day of chemotherapy and continued through day 5 for the first chemotherapy cycle, whereas dex was titrated down on days 2-4. The primary end point was complete response (CR), defined as no emesis and no use of rescue medications on days 2-6, using an NV diary. The percentages of those in each group with a CR were compared by Fisher's exact test., Results: Four hundred thirty patients were enrolled in this study. Forty-seven percent of patients in the gabapentin arm and 41% in the placebo arm had a CR (P = .23). Mean number of emesis episodes was <0.5 daily, and mean nausea severity was < 2 (mild). In both arms, patient satisfaction with NV control was greater than 8 (with 10 being perfectly satisfied). There were no significant differences in unwanted side effects., Conclusions: In this study, gabapentin did not significantly improve delayed NV. Patients were satisfied with the control of their nausea and vomiting irrespective of arm. The use of a 5HT3 RA and dexamethasone provided good control of nausea and vomiting for most patients., (© 2014 American Cancer Society.)

Background: Cisplatin reduces plasma ghrelin levels through the 5-hydroxytryptamine (5-HT) receptor. This may cause cisplatin-induced gastrointestinal disorders and hinders the continuation of chemotherapy. The authors of this report conducted a prospective, randomized phase 2 trial to evaluate the effects of exogenous ghrelin during cisplatin-based chemotherapy., Methods: Forty-two patients with esophageal cancer who were receiving cisplatin-based neoadjuvant chemotherapy were assigned to either a ghrelin group (n = 21) or a placebo group (n = 21). They received either intravenous infusions of synthetic human ghrelin (3 μg/kg) or saline twice daily for 1 week with cisplatin administration. The primary endpoint was changes in oral calorie intake, and the secondary endpoints were chemotherapy-related adverse events; appetite visual analog scale (VAS) scores; changes in gastrointestinal hormones and nutritional status, including rapid turnover proteins, and quality of life (QoL) estimated with the European Organization for Research and Treatment of Cancer QoL core questionnaire (QLQ-C30)., Results: Two patients were excluded from the final analysis: One patient suspended ghrelin administration because of excessive diaphoresis, and another patient in the placebo group failed to monitor the self-questionnaire. Food intake and appetite VAS scores were significantly higher in the ghrelin group than in the placebo group (18.2 ± 5.2 kcal/kg/day vs 12.7 ± 3.4 kcal/kg/day [P = .001] and 6.2 ± 0.9 vs 4.1 ± 0.9 [P < .0001], respectively). Patients in the ghrelin group had fewer adverse events during chemotherapy related to anorexia and nausea than patients in the control group. Significant deterioration was noted after chemotherapy in the placebo group in QoL scores, appetite, nausea and vomiting, and global health status., Conclusions: Short-term administration of exogenous ghrelin at the start of cisplatin-based chemotherapy stimulated food intake and minimized adverse events., (Copyright © 2012 American Cancer Society.)

Background: This randomized, double-blind, dose-ranging, placebo-controlled, phase 2 trial evaluated the neurokinin-1 receptor antagonist casopitant mesylate in combination with ondansetron/dexamethasone (ond/dex) for the prevention of chemotherapy-induced nausea and vomiting (CINV) related to moderately emetogenic chemotherapy (MEC)., Methods: Chemotherapy-naive patients who were receiving MEC (N=723) were randomized to receive either oral placebo or casopitant at doses of 50 mg, 100 mg, or 150 mg daily (on Days 1-3) plus ondansetron (on Days 1-3) and dexamethasone (Day 1). Two exploratory arms evaluated single-dose casopitant (150 mg) plus ond/dex and a 3-day casopitant regimen with once-daily ondansetron and dexamethasone. Primary endpoints were rates of complete response (CR) (no vomiting, retching, rescue therapy, or premature discontinuation) and significant nausea (SN) (>or=25 mm on a visual analog scale) over the first 120 hours after Cycle 1 of MEC. Secondary endpoints included acute and delayed CR and SN rates, rates of nausea, vomiting, and safety., Results: All casopitant doses that were tested significantly increased the proportion of patients with CR: The CR rates were 80.8% with casopitant 50 mg, 78.5% with casopitant 100 mg, and 84.2% with casopitant 150 mg compared with 69.4% in the control group (P=.0127); casopitant 150 mg was identified as the minimally effective dose. In exploratory analyses, single-dose casopitant demonstrated a 79.2% CR rate, and once-daily ondansetron plus casopitant produced an 83.5% CR rate. Vomiting rates in the first 5 days after MEC were reduced with casopitant-containing regimens (from 23% to 10%-16%). Rates of SN did not differ among treatment arms (range, 28%-29%). Casopitant appeared to be well tolerated with no notable differences in overall adverse event frequency., Conclusions: Casopitant plus ond/dex was more effective than ond/dex alone for the prevention of CINV., (Copyright (c) 2009 American Cancer Society.)

Background: The objective of this study was to assess which quality-of-life (QOL) line items on the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) were associated with low QOL in women who were receiving chemotherapy for ovarian cancer., Methods: Patients with stage III or IV ovarian cancer on Gynecologic Oncology Group Protocols 152 and 172 who underwent primary surgery followed by intravenous paclitaxel and cisplatin completed the FACT-O. The FACT scale includes the 4 domains of physical, functional, social, and emotional well being (PWB, FWB, SWB, EWB, respectively). Women who had overall FACT-O scores in the lowest quartile (Q1) were compared with women in the upper 3 quartiles (Q2-Q4). The proportions of women in each group that selected the 2 worst categories for each item were compared. The level of significance was set at P<.005., Results: Before Cycle 4, 361 patients (86.4%) provided valid QOL assessments. For PWB, a significantly greater proportion of women in Q1 versus Q2 through Q4 selected the 2 worst categories of several physical symptoms (nausea, pain, feeling ill, and being bothered by the side effects of treatment). For FWB, significant differences included being able to work, being content with the quality of their life, and sleeping well. For EWB, there were significant differences in feeling nervous and worrying about dying. There were virtually no differences between groups in SWB. Low interest in sex was reported by 56% to 88% of all patients (Q1-Q4)., Conclusions: A large proportion of women with FACT-O scores in the lowest quartile reported problems that potentially were amenable to clinical interventions, such as symptom management and psychosocial support., (Copyright (c) 2009 American Cancer Society.)

Background: Increasing evidence suggests a relation between patient expectancies and chemotherapy-induced nausea. However, this research has often failed to adequately control for other possible contributing factors. In the current study, the contribution of patient expectancies to the occurrence and severity of postchemotherapy nausea was examined using more stringent statistical techniques (namely hierarchical regression) than other similar studies that have relied on bivariate correlations, chi-square tests, and stepwise regression, and further extended upon previous research by including quality of life (QoL) in the analysis., Methods: In all, 671 first-time chemotherapy patients taking part in a trial comparing antiemetic regimens answered questions regarding their expectancies for experiencing nausea. Patients then completed a diary assessing both the occurrence and severity of their nausea in the 4 days after their first infusion., Results: Stronger expectancies for nausea corresponded with greater average and peak nausea after chemotherapy and this was after controlling for age, sex, susceptibility to motion sickness, diagnosis, and QoL. Interestingly, patients classified as highly expectant (first quartile) experienced significantly greater average and peak nausea than those classified as somewhat expectant, slightly expectant, and not expectant (second, third, and fourth quartiles, respectively), whereas there were no significant differences between these lower levels of expectancy. Furthermore, increases in average nausea led to a significant reduction in QoL after chemotherapy., Conclusions: Patient expectancies appear to contribute to postchemotherapy nausea and patients that are highly expectant of experiencing nausea appear to be at particular risk. Interventions that target these patients should reduce the burden of nausea and may also improve QoL., ((c) 2008 American Cancer Society)

Background: The safety and efficacy of the fully human antibody panitumumab was evaluated in patients with metastatic colorectal cancer refractory to available therapies., Methods: This phase 2 open-label, multicenter study of panitumumab enrolled patients with metastatic colorectal cancer who had progressed on chemotherapy that included a fluoropyrimidine and irinotecan or oxaliplatin, or both. All patients had tumors with > or =10% 1+ epidermal growth factor receptor (EGFr) staining by immunohistochemistry. Patients were stratified into 2 strata (high or low staining intensity) and received intravenous panitumumab 2.5 mg/kg weekly 8 of every 9 weeks until disease progression or unacceptable toxicity., Results: In all, 148 patients received panitumumab, 105 in the high EGFr stratum, 43 in the low EGFr stratum. Overall response by central review was 9% (95% confidence interval [CI], 5%-15%) and was similar between strata. An additional 29% of patients had stable disease. Median progression-free survival was 14 weeks (95% CI, 8-16) and median overall survival was 9 months (95% CI, 6-10). Toxicities were manageable, with skin toxicity reported in 95% of patients (5% grade 3 or 4). Four patients discontinued therapy because of toxicity. No antipanitumumab antibodies were detected. One patient had an infusion reaction but was able to continue therapy., Conclusions: Panitumumab given weekly was well tolerated and had single-agent activity in previously treated patients with colorectal cancer. Dermatologic toxicity was common but rarely severe. Ongoing studies will determine panitumumab activity earlier in the course of treatment for colorectal cancer and in combination with other antineoplastic agents.

Background: The optimal trastuzumab-based chemotherapy regimen for HER2-overexpressing, metastatic breast cancer is not known. The trastuzumab and vinorelbine or taxane (TRAVIOTA) study was a prospective, multicenter, randomized trial that was designed to compare these regimens., Methods: Eligible patients had HER2-overexpressing, metastatic breast cancer and had received no prior chemotherapy for advanced disease. Patients were randomized 1:1 to receive either trastuzumab with weekly vinorelbine therapy or weekly taxane therapy (paclitaxel or docetaxel at the investigator's choice). Originally planned for 250 patients, the study was closed because of poor accrual with 81 evaluable patients, including 41 patients who received vinorelbine and 40 patients who received taxane., Results: Response rates were 51% and 40% for the vinorelbine/trastuzumab arm and the taxane/trastuzumab arm, respectively (Fisher exact test; P = .37). The median time to disease progression was 8.5 months and 6.0 months for the vinorelbine- and taxane-based arms, respectively (log-rank test; P = .09). Treatment with either regimen generally was well tolerated, yielding comparable rates of neurologic and gastrointestinal toxicity. Vinorelbine-based treatment was associated with more anemia and neutropenia and with 2 episodes of cardiotoxicity. Taxane-based therapy was associated with more dermatologic toxicity, myalgias, and fluid retention., Conclusions: Both vinorelbine/trastuzumab and taxane/trastuzumab treatments were active as first-line therapy for HER2-positive, metastatic breast cancer and had comparable rates of efficacy and tolerability. The toxicities observed were the result of recognized side effects associated with each of the chemotherapy agents and schedules. These data can inform treatment decision making in this clinical setting.

Background: Chemotherapy-induced nausea and vomiting (CINV) is among the most feared side effects of cancer treatment. Poorly controlled CINV may lead to additional office visits or emergency room admissions, thus increasing the overall costs of cancer care. The objective of the project was to estimate the societal costs of uncontrolled CINV among working-age cancer patients., Methods: The 1997-2002 Health and Productivity Management database, a proprietary database linking medical claims to work loss information, was used. The study population consisted of employees or their spouses who were cancer patients treated with highly or moderately emetogenic chemotherapy regimens. Costs of uncontrolled CINV were estimated by comparing the direct medical costs and indirect costs between those with and without uncontrolled CINV; all costs were normalized as monthly costs and updated to 2006 US dollars. The Wilcoxon Mann-Whitney test was used to compare the costs differences in univariate analyses, followed by multivariate analyses., Results: In all, 2,018 patients were identified; 1,771 (88%) received 5-HT(3) receptor antagonists, and uncontrolled CINV was found in 563 (28%). The estimated monthly medical costs associated with uncontrolled CINV were approximately 1,300 dollars higher for cancer patients at working ages. Subgroup analysis concluded that indirect costs per patient per month were 433 dollars higher for those in the uncontrolled CINV group., Conclusions: Despite a prevalent use of the 5-HT(3) receptor antagonists, uncontrolled CINV remained a common and costly problem among cancer patients treated with highly or moderately emetogenic chemotherapy., ((c) 2007 American Cancer Society.)

Background: Hepatic arterial infusion chemotherapy (HAIC) has often been selected as a therapeutic option for patients with advanced hepatocellular carcinoma (HCC). The objective of the current study was to evaluate the efficacy and safety of repetitive HAIC with high-dose 5-fluorouracil (5-FU) and cisplatin given for 3 days in patients with advanced HCC., Methods: Between January 2001 and December 2004, a total of 41 patients with unresectable advanced HCC were enrolled. The patients underwent HAIC via the implantable port system with 5-FU (at a dose of 500 mg/m(2) on Days 1-3) and cisplatin (at a dose of 60 mg/m(2) on Day 2) every 4 weeks. Tumor response was assessed at the end of every 3 cycles., Results: The median age of the patients was 53 years and 34 patients (82.9%) had evidence of portal vein thrombosis. In total, 230 cycles of HAIC were administered to the 41 patients, with a median of 6 cycles given (range, 1-14 cycles). Nine patients (22.0%) achieved a partial response and 14 patients (34.1%) had stable disease. The median time to disease progression and overall survival were 7.0 months and 12.0 months, respectively. The overall survival was found to be significantly longer in the successful disease control group (patients with a complete response, partial response, and stable disease) than in the disease progression group (median of 14.0 months vs 6.0 months; P < .001). Adverse reactions were tolerable and successfully managed with conservative treatment., Conclusions: HAIC with high-dose 5-FU and cisplatin given for 3 days achieved effective and safe results in patients with advanced HCC. Therefore, repetitive short-course HAIC with high-dose 5-FU and cisplatin may be useful as an alternative therapeutic option for patients with advanced HCC., (Copyright (c) 2007 American Cancer Society.)

Background: Homoharringtonine (HHT) is a cephalotaxus alkaloid that inhibits the synthesis of proteins leading to apoptosis. Intravenous HHT has demonstrated activity in patients with chronic myeloid leukemia (CML) after failure with interferon., Methods: A Phase I study was completed of subcutaneous (s.c.) HHT in patients with CML in accelerated or blast phases and demonstrated efficacy and good tolerance at the same doses used by intravenous (i.v.) administration. The maximal tolerated dose (MTD) was 1.25 mg/m(2) s.c. twice daily. The cohort was then expanded to treated at the MTD to include patients in late chronic phase CML after imatinib failure. Therapy consisted of an i.v. loading dose of HHT 2.5 mg/m(2) over 24 hours, followed by 1.25 mg/m(2) s.c. twice daily for 14 days every 28 days until remission, then for 7 days every 28 days. Six patients (median age, 53 years) who had failed imatinib were treated and 5 were evaluable. Patients received a median of 4.5 courses of s.c. HHT., Results: Complete hematologic remission was obtained in all 5 evaluable patients and 3 had cytogenetic (CG) responses: 1 complete and 2 minor. The 2 patients with BCR-ABL kinase domain mutations at the start of therapy with HHT had a CG response and in both instances the mutations became undetectable. All patients developed myelosuppression and 3 had their HHT dose reduced due to prolonged neutropenia. Nonhematologic toxicity was mild and manageable., Conclusions: Subcutaneous HHT is well tolerated and may have clinical activity in patients with CML after imatinib failure.

Background: A single-institution Phase I clinical trial was conducted to determine the maximum tolerated dose (MTD) and define the safety profile of temozolomide and capecitabine when used in combination to treat brain metastases from breast cancer., Methods: Patients were eligible if they had bidimensionally measurable supratentorial or infratentorial brain metastasis from histologically confirmed breast carcinoma. Patients could have received up to 3 prior chemotherapy regimens. Temozolomide and capecitabine were administered concomitantly to 4 sequential cohorts at different dosing levels on Days 1-5 and Days 8-12, with cycles repeated every 21 days until disease progression., Results: Twenty-four patients with multiple brain lesions were treated, including 14 patients with newly diagnosed brain metastases and 10 patients with recurrent brain metastases. Only 1 patient was chemotherapy-naive. Fatigue and nausea were the most commonly observed toxicities observed at any dose levels. Significant antitumor activity was observed, with a total of 1 complete and 3 partial responses (18% objective response rate) in the brain. The median response duration was 8 weeks (range, 6-64 weeks) and the median time to progression in the brain was 12 weeks (range, 3-70 weeks). Neurocognitive function improved or remained stable in patients with a response or stable disease., Conclusions: The combination of temozolomide and capecitabine is an active, well-tolerated regimen. The observed antitumor activity warrants further evaluation of this combination as an alternative to or in combination with whole-brain radiation therapy for the treatment of multiple brain metastases., ((c) 2006 American Cancer Society.)

Background: The purpose of the current study was to determine the maximum tolerated dose, dose-limiting toxicities, pharmacokinetic profile, and recommended Phase II dose of oral administration of TAS-102, a novel nucleoside formed by the combination of alpha,alpha,alpha-trifluorothymidine (FTD) and a thymidine phosphorylase inhibitor (TPI: 5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4(1H,3H)-pyrimidinedione)., Methods: Eligible patients had advanced solid tumors, adequate organ function, and had not received anticancer therapy in the preceding 4 weeks. TAS-102 was administered orally once daily for 14 days, followed by a 1-week rest, repeated every 3 weeks. The initial dose of TAS-102 administered was 100 mg/m2/day. The first 2 patients treated at that dose experienced substantial toxicity and, therefore, lower dose levels of TAS-102 were subsequently explored., Results: Fourteen patients were enrolled; all patients were evaluable for toxicity assessment and 12 were evaluable for response. The initial dose explored was 100 mg/m2/day, based on a preclinical monkey model. However, the first 2 patients experienced bone marrow suppression of Grade 3 or 4 in course 1. The protocol was amended to study the next cohort of patients at 50 mg/m2/day. At this dose level no Grade 3 or 4 toxicities were observed in course 1. In the subsequent dose level (60 mg/m2/day), 3 of 6 patients experienced Grade 3 or 4 granulocytopenia as dose-limiting toxicity. Three additional patients for a total of 6 were enrolled at 50 mg/m2/day without occurrence of dose-limiting toxicity. Thus, 50 mg/m2/day was declared the maximum tolerated dose for this schedule., Conclusions: The authors' study showed that 50 mg/m2/day was a tolerable dose of the novel antimetabolite FTD in combination with an inhibitor of its inactivating enzyme TP, and this is the recommended Phase II dose. Evaluation of this daily dose in malignancies for which fluoropyrimidines have failed is needed., ((c) 2006 American Cancer Society.)

Background: The purpose of the study was to determine the activity and toxicity of pulse dactinomycin as salvage treatment of patients with low-risk gestational trophoblastic neoplasia (GTN) who failed methotrexate therapy., Methods: Eligible patients had persistent/recurrent low-risk GTN defined by changes in serum human chorionic gonadotropin (hCG) levels (<10% fall over 3 consecutive weekly titers, >20% rise over the previous value, or a rise after attaining institutional normal [>5 mu/mL]); World Health Organization (WHO) score 2-6; Gynecologic Oncology Group (GOG) performance status 0-1; and previous treatment restricted to methotrexate. Dactinomycin administration was 1.25 mg/m2 intravenous (i.v.) every 2 weeks until documented complete response (CR) or treatment failure. CR was defined as an institutional normal serum hCG level sustained for >or=4 consecutive weeks; treatment failure was a <10% fall (3 assays over 4 weeks) or >20% rise (over previous value) in hCG serum level. Levels were monitored biweekly x 8 weeks beyond the first normal value, then monthly x 10., Results: Five of 44 enrolled patients were ineligible due to choriocarcinoma and normal pretreatment serum hCG level (2 each), no history of methotrexate (1), and 1 patient with documented phantom hCG syndrome was unevaluable. In all, 28 of 38 (74%) evaluable patients attained CR. The median number of cycles was 4 (range, 2-10). Severe toxicity was minimal, causing no patient to discontinue therapy. All treatment failures achieved a CR after receiving subsequent chemotherapy; 3 patients also underwent hysterectomy., Conclusion: Pulse dactinomycin is an active regimen for patients with low-risk GTN who fail previous methotrexate therapy., ((c) 2006 American Cancer Society.)

Background: To the authors' knowledge there is little information available regarding the effectiveness of standard antiemetic therapy among cancer patients who receive emetogenic chemotherapy in clinical practice, especially in the pediatric population. The current study was undertaken to determine the effectiveness of standard antiemetic interventions among children receiving emetogenic chemotherapy., Methods: The authors conducted a retrospective review of antiemetic surveys for children who received emetogenic chemotherapy. Patients and/or their parents were surveyed for acute and delayed nausea and emesis after each course of emetogenic chemotherapy. The survey consisted of validated measures of the severity of nausea and emesis. Complete protection (CP) rates were calculated for each chemotherapy regimen during both the acute and delayed phases and also by gender and age group (ages birth-3 yrs, 4-11 yrs, and 12-20 yrs). Antiemetic therapy consisted of intravenous ondansetron administered once daily during chemotherapy either alone (for moderately emetogenic chemotherapy) or in combination with dexamethasone (for severely emetogenic chemotherapy)., Results: In total, 224 different patients completed 1256 surveys. CP from both acute and delayed nausea and emesis was more likely in the children ages birth-3 years than in older children. For moderately emetogenic regimens, nausea and emesis in the acute and delayed phases were controlled well. Among severely emetogenic chemotherapy regimens, 7 of 12 different regimen types had CP rates < 50% in either the acute phase or the delayed phase. CP rates were particularly low for cisplatin-based and cyclophosphamide-based regimens., Conclusions: Nausea and emesis remain significant problems among children who receive emetogenic chemotherapy. CP rates were associated significantly with patient age, and higher rates were observed among very young children., (Copyright 2006 American Cancer Society.)

Background: An aprepitant (APR) regimen was evaluated for prevention of nausea and emesis due to moderately emetogenic chemotherapy (MEC) over multiple cycles., Methods: The authors performed a randomized, double-blind study. Eligible patients with breast carcinoma were naïve to emetogenic chemotherapy and treated with cyclophosphamide alone or with doxorubicin or epirubicin. Patients were randomized to receive either an APR regimen (Day 1: APR 125 mg, ondansetron [OND] 8 mg, and dexamethasone [DEX] 12 mg before chemotherapy and OND 8 mg 8 hrs later; Days 2-3: APR 80 mg every day) or a control regimen (Day 1: OND 8 mg and DEX 20 mg before chemotherapy and OND 8 mg 8 hrs later; Days 2-3: OND 8 mg twice per day). Data on nausea, emesis, and use of rescue medication were collected. The primary end point was the proportion of patients with a complete response (CR; no emesis or use of rescue therapy) in Cycle 1. Efficacy end points for the multiple-cycle extension were the probabilities of a CR in Cycles 2-4 and a sustained CR rate across multiple cycles., Results: Of 866 patients randomized, 744 (85.9%) entered the multiple-cycle extension, and 650 (75.1%) completed all 4 cycles. Overall, the CR was greater with the APR regimen over the 4 cycles: 53.8% versus 39.4% for Cycle 2, 54.1% versus 39.3% for Cycle 3, and 55.0% versus 38.4% for Cycle 4. The cumulative percentage of patients with a sustained CR over all 4 cycles was greater with the APR regimen (P = 0.017)., Conclusions: The APR regimen was more effective than a control regimen for the prevention of nausea and emesis induced by MEC over multiple chemotherapy cycles.

Background: Nausea and emesis as a consequence of chemotherapy or radiotherapy can have an adverse effect on patients' quality of life during cancer treatment and may last for > 5 days after administration. Guidelines suggest that, used at appropriate doses, the 5-hydroxytryptamine type-3 (5-HT3) receptor antagonists--which are considered the antiemetic "gold standard" when they are administered in combination with corticosteroids--demonstrate equivalent efficacy and safety. However, due to financial considerations, these agents often are used at lower doses than recommended., Methods: A literature review of relevant publications pertaining to the control of chemotherapy-induced nausea and emesis and dosing issues of the 5-HT3 receptor antagonists was undertaken to provide a comprehensive review of dosing issues relevant to the 5-HT3 receptor antagonists., Results: The issue of "down dosing" was particularly pertinent because of the nature of the 5-HT3 receptor antagonist dose-response curve: A steep dose-response profile within a narrow dose range suggests that antiemetic control will be lost suddenly after dose deescalation. However, the array of predisposing and confounding patient factors indicates that it is unlikely that a loss of antiemetic control will be apparent across a population; rather, individuals will experience loss of control as the dose is reduced below threshold. Of the 4 5-HT3 receptor antagonists currently licensed in the United States (granisetron, ondansetron, dolasetron, and palonosetron), ondansetron is used sometimes at lower than optimal doses, and there is evidence to suggest that even the approved oral dose of dolasetron may be suboptimal., Conclusions: Suboptimal dosing not only will be detrimental to patients' quality of life but, ultimately, will prove counterproductive in terms of hospital resources, and it will add to the already significant socioeconomic burden associated with cancer therapy. Therefore, the dose of antiemetic agent administered should be sufficiently high to ensure good emesis control across the whole patient population.

Background: Imatinib inhibits the c-kit tyrosine kinase, which, accounts for its activity in gastrointestinal stromal tumors. The presence of c-kit protein expression in small cell lung carcinoma (SCLC) tumor specimens, as well as in vitro data supporting the role of c-kit in autocrine and paracrine growth stimulation specifically in SCLC, provided a rationale for studying imatinib in this disease. The authors conducted a Phase II single-institution study of imatinib in patients with recurrent SCLC whose tumor specimens expressed c-kit protein., Methods: Patients with progressive SCLC after one or two previous chemotherapy regimens consented to have their tumor specimens screened by immunoperoxidase stain (CD117, Dako Corporation, Carpinteria, CA) for c-kit protein expression. If present, individuals were then eligible for treatment with an imatinib dose of 400 mg orally twice daily (total, 800 mg per day)., Results: The presence of c-kit protein was assessable in 36 of 39 (92%) tumor samples. Twenty-eight (78%) tumor samples had immunohistochemical staining for c-kit protein. Twelve patients were enrolled in the treatment portion of the current study. No responses were observed, and all patients had disease progression by Week 4. Edema, fatigue, nausea, and electrolyte abnormalities were the primary toxicities., Conclusions: Imatinib did not have antitumor activity against SCLC, even with c-kit protein present in tumor specimens. The dismal prognosis for these patients with progressive SCLC emphasized the urgent need for continued studies of new therapies in this population.

Background: Patients may use their past experiences with nausea, as well as information about the incidence of nausea from chemotherapy that other patients have experienced, to form a prediction, or response expectancy, of nausea from their own upcoming chemotherapy. Mounting evidence suggests that these expectancies relating to nausea are significant predictors, and, likely, contributing factors to the development of treatment-related nausea., Methods: The patients in the current study were participants in the control arm of a multicenter clinical trial conducted between November 1999 and July 2001 by the University of Rochester Community Clinical Oncology Program. All patients in the current report were age >/= 18 years and were about to begin a first cancer treatment regimen containing doxorubicin., Results: Expectancy of nausea assessed before patients received their first doxorubicin-based chemotherapy treatment was found to be a strong predictor of subsequent nausea and in fact was stronger than previously reported predictive factors, including age, nausea during pregnancy, and susceptibility to motion sickness. Women who believed it was "very likely" that they would have severe nausea from chemotherapy were five times more likely to experience severe nausea than fellow patients who thought its occurrence would be "very unlikely.", Conclusions: Further studies confirming an expectancy of nausea as a risk factor are warranted as are studies examining the benefit to a patient's quality of life from modifying antiemetic treatment guidelines to take into account symptom expectancies. Finally, ethically acceptable interventions that are designed to reduce patients' nausea expectancies or increase their expectancies of nausea control should be developed and studied., ((c) 2004 American Cancer Society)

Background: The authors determined the incidence of acute and delayed chemotherapy-induced nausea and emesis (vomiting) (CINV) among patients receiving highly (HEC) or moderately (MEC) emetogenic chemotherapy. They also assessed whether physicians and nurses accurately recognized the incidence of acute and delayed CINV in their own practices., Methods: A prospective, observational study of adult patients receiving HEC or MEC for the first time was performed. Before patient enrollment, medical oncologists and oncology nurses estimated the incidence of acute (Day 1) and delayed (Days 2-5) CINV after first administration of HEC and MEC in their own practices. Eligible patients from their practices then completed a 6-day diary including emetic episodes, nausea assessment, and antiemetic medication use. Observed incidence rates of acute and delayed CINV were compared with physician/nurse predictions., Results: Twenty-four physicians and nurses and 298 eligible patients (67 receiving HEC and 231 receiving MEC) were recruited from 14 oncology practices in 6 countries. Greater than 35% of patients overall experienced acute nausea, whereas 13% experienced acute emesis. Delayed nausea and emesis were observed in 60% and 50% of HEC patients, respectively, and in 52% and 28% of MEC patients, respectively. Delayed symptoms appeared without acute symptoms after HEC (emesis, 38%; nausea, 33%) and MEC (emesis, 19%; nausea, 21%). Physicians and nurses accurately predicted the incidence of acute CINV but underestimated the incidence of delayed nausea and emesis after HEC by 21 and 28 percentage points, respectively, and delayed nausea after MEC by 28 percentage points. Greater than 75% of physicians and nurses underestimated the incidence of delayed CINV after both HEC and MEC., Conclusions: Physicians and nurses markedly underestimated the incidence of delayed nausea and emesis after both HEC and MEC. Delayed nausea and emesis, which may appear even in the absence of acute nausea and emesis, remain important targets for improved therapeutic intervention., (Copyright 2004 American Cancer Society.)

Background: Chemotherapy-induced nausea and emesis (CINE) is one of the most dreaded side effects of cancer therapy. To investigate the influence of these symptoms on a patient's quality of life (QOL), a validated tool measuring many domains is needed., Methods: A QOL questionnaire consisting of scales from the European Organization for Research and Treatment of Cancer QLQ-C30, the Morrow Assessment of Nausea and Emesis, the Osoba Nausea and Emesis Module, and new items specific to nausea, emesis, and retching was constructed and administered daily for 7-9 days to outpatients receiving emetogenic chemotherapy., Results: Test-retest and internal consistency reliabilities ranged from 0.44 to 0.84 and from 0.59 to 0.85, respectively. Item and scale correlations indicated good convergent and discriminant validity. Scales and items measuring similar factors (e.g., severity of emesis and severity of nausea) had strong correlations than did scales measuring dissimilar factors (e.g., cognitive functioning and physical functioning). The validity of known groups was demonstrated by significant differences (P < 0.01) in patients' QOL scores between days with no episodes of nausea, emesis, or retching, days with 1 or 2 episodes, and days with more than 3 episodes. Patients' QOL significantly decreased as the number of episodes per day increased (P < 0.001)., Conclusions: A CINE QOL questionnaire that successfully measures the short-term impact of nausea, emesis, and retching on patients receiving emetogenic chemotherapy has been developed, largely as a battery of preexisting questionnaires. The psychometric properties of the new questionnaire show adequate reliability and validity to warrant its use in clinical trials and outcomes studies. CINE adversely affects many domains within a patient's QOL., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11540)

Background: Aprepitant is a novel neurokinin 1 (NK(1)) antagonist that has been shown to improve control of chemotherapy-induced nausea and vomiting (CINV) when added to a standard antiemetic regimen of a 5-hydroxytriptamine-3 antagonist plus a corticosteroid. The authors sought to evaluate further the efficacy and tolerability of aprepitant plus standard therapy in a large clinical trial., Methods: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-groups, Phase III study. Patients with cancer who were scheduled to receive treatment with high-dose cisplatin chemotherapy were randomized to receive 1 of 2 treatment regimens; the standard therapy group received intravenous ondansetron 32 mg and oral dexamethasone 20 mg on Day 1, and oral dexamethasone 8 mg twice daily on Days 2-4. The aprepitant group received oral aprepitant 125 mg, intravenous ondansetron 32 mg, and oral dexamethasone 12 mg on Day 1; oral aprepitant 80 mg and oral dexamethasone 8 mg once daily on Days 2-3; and oral dexamethasone 8 mg on Day 4. Patients recorded episodes of emesis, use of rescue therapy, and severity of nausea in a diary. A modified intent-to-treat approach was used to analyze the efficacy data. The primary endpoint was complete response (no emesis and no rescue therapy) during the 5-day period postcisplatin. Treatment comparisons were made using logistic regression models, and reported adverse events and physical and laboratory assessments were used to assess tolerability., Results: A total of 523 patients were evaluated for efficacy, and 568 patients were evaluated for safety. During the 5 days after chemotherapy, the percentages of patients who achieved a complete response were 62.7% in the aprepitant group (163 of 260 patients) versus 43.3% in the standard therapy group (114 of 263 patients; P < 0.001). For Day 1, the complete response rates were 82.8% for the aprepitant group and 68.4% for the standard therapy group (P < 0.001); for Days 2-5, the complete response rates were 67.7% in the aprepitant group and 46.8% in the standard therapy group (P < 0.001). The overall incidence of adverse events was similar between the 2 treatment groups (72.8% in the aprepitant group [206 of 283 patients] and 72.6% in the standard therapy group [207 of 285 patients]) as were rates of serious adverse events, discontinuations due to adverse events, and deaths., Conclusions: In patients with cancer who are receiving high-dose cisplatin-based chemotherapy, therapy consisting of aprepitant (125 mg on Day 1 and 80 mg on Days 2-3) plus a standard regimen of ondansetron and dexamethasone provided superior antiemetic protection compared with standard therapy alone and was generally well tolerated., (Copyright 2003 American Cancer Society.)

Background: Clinical reports suggest that nausea remains a side effect of chemotherapy despite widespread use of serotonin receptor antagonists. This study summarized the frequency, timing, and intensity of postchemotherapy nausea for patients receiving doxorubicin, cisplatin, or carboplatin., Methods: Three hundred sixty chemotherapy-naïve patients (73% female) were enrolled in a study testing the ability of an information intervention to reduce nausea. Of these, 322 subjects completed the Morrow Assessment of Nausea and Emesis (MANE), as well as a 5-day self-report diary, at Cycle 1 (300 subjects completed the MANE and self-report diary at Cycle 2). All patients received a 5-hydroxytryptamine-3 receptor antagonist (ondansetron) with dexamethasone on the day of treatment., Results: Seventy-six percent of the patients developed nausea during the 5-day period, beginning with the Cycle 1 infusion, and 73% of patients reported delayed nausea (DN) during Days 2-5. The proportions were similar during Cycle 2. Fifty-five percent of patients described their DN as being of moderate or greater intensity compared with 28% of patients who described acute nausea. Carboplatin was less likely to cause DN than either of the other agents (56% of 106 patients compared with 75% of 47 receiving cisplatin and 83% of 169 taking doxorubicin). The mean peak DN severity was 4.34 (range, 1-7) for doxorubicin, which was significantly higher than the mean peak value for carboplatin (3.66) but was not significantly different from the mean peak value for cisplatin (4.26). Eighteen percent of patients did not experience nausea until Day 3 or later., Conclusions: Despite prophylaxis with ondansetron, the majority of patients receiving one of these common chemotherapy agents experienced nausea. The frequency of DN was nearly twice that of acute nausea. Results show the need for continued development of antiemetics that are effective against DN., (Copyright 2003 American Cancer Society.)

Background: The neurokinin-1 antagonist aprepitant (EMEND; Merck Research Laboratories, West Point, PA) has been shown to reduce chemotherapy-induced nausea and vomiting when it is given with a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone. The current study sought to define the most appropriate dose regimen of oral aprepitant., Methods: This multicenter, randomized, double-blind, placebo-controlled study was conducted in patients with cancer who were receiving initial cisplatin (> or = 70 mg/m(2)) and standard antiemetic therapy (intravenous ondansetron plus oral dexamethasone). Patients were randomized to receive standard therapy plus either aprepitant 375 mg on Day 1 and 250 mg on Days 2-5, aprepitant 125 mg on Day 1 and 80 mg on Days 2-5, or placebo. Due to an apparent interaction with dexamethasone suggested by pharmacokinetic data obtained while the study was ongoing, the aprepitant 375/250 mg dose was discontinued and replaced with aprepitant 40 mg on Day 1 and 25 mg on Days 2-5, and a new randomization schedule was generated. Patients recorded nausea and emesis in a diary. The primary endpoint was complete response (no emesis and no rescue therapy), which was analyzed using an intent-to-treat approach with data obtained after the dose adjustment. Treatment comparisons were made using logistic regression models. Tolerability was assessed by reported adverse events and physical and laboratory assessments, and included all available data., Results: The percentages of patients who achieved a complete response in the overall study period were 71.0% for the aprepitant 125/80-mg group (n = 131 patients), 58.8% for the aprepitant 40/25-mg group (n = 119 patients), and 43.7% for the standard therapy group (n = 126 patients; P < 0.05 for either aprepitant regimen vs. standard therapy). Rates for Day 1 were 83.2% for the aprepitant 125/80-mg group, 75.6% for aprepitant 40/25-mg group, and 71.4% for the standard therapy group (P < 0.05 for aprepitant 125/80 mg vs. standard therapy), and rates on Days 2-5 were 72.7% for the aprepitant 125/80-mg group, 63.9% for the aprepitant 40/25-mg group, and 45.2% for the standard therapy group (P < 0.01 for either aprepitant group vs. standard therapy). The efficacy of the aprepitant 375/250-mg regimen was similar to that of the aprepitant 125/80-mg regimen. The overall incidence of adverse events was generally similar across treatment groups: 85% in the aprepitant 375/250-mg group (n = 34 patients), 76% in the aprepitant 125/80-mg group (n = 214 patients), 71% in the aprepitant 40/25-mg group (n = 120 patients), and 72% in the standard therapy group (n = 212 patients), with the exception of a higher incidence of infection in the aprepitant 125/80-mg group (13%) compared with the standard therapy group (4%)., Conclusions: When it was added to a standard regimen of intravenous ondansetron and oral dexamethasone in the current study, aprepitant reduced chemotherapy-induced nausea and vomiting and was generally well tolerated, although increases in infection were noted that were assumed to be due to elevated dexamethasone levels as a result of the pharmacokinetic interaction. The aprepitant 125/80-mg regimen had the most favorable benefit:risk profile., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11320)

Background: This Phase II multicenter, open-label, single-arm study evaluated the efficacy and safety of a three-drug combination of irinotecan (CPT-11), paclitaxel, and carboplatin in advanced nonsmall cell lung carcinoma (NSCLC)., Methods: Patients received repeated 21-day cycles at starting doses of paclitaxel 175 mg/m(2) administered over 3 hours, followed by carboplatin AUC of 5 over 30 minutes and CPT-11 at a starting dose level of 100 mg/m(2) over 90 minutes, all given on the first day of each cycle. Patients were evaluated for objective tumor response, time to tumor progression (TTP), survival, and safety., Results: Forty patients were enrolled. Baseline patient characteristics included: median age 58 years (range, 32-79); 23 males and 17 females; performance status of 0 (21 patients), 1 (18 patients), or 2 (1 patient); and Stage IIIB (10 patients) and Stage IV (30 patients) disease. A median of six cycles (range, one to eight) were administered. Grade 3-4 toxicities observed in >/= 10% of the patients included neutropenia (78%), asthenia (20%), diarrhea (20%), nausea (18%), vomiting (13%), anemia (10%), and dyspnea (10%). Febrile neutropenia occurred in eight patients (20%), with one death due to neutropenic sepsis. Twelve of 38 evaluable patients had confirmed tumor responses (32%), while 21 (55%) had stable disease (including 12 patients [32%] with minor responses). Only 13% had disease progression at their initial tumor assessment. The median TTP and survival were 5.3 months (range, 0.03-6.2 months) and 12.5 months (range 0.3-28.6+ months), respectively. The one and two year survival probabilities were 0.50 (95% confidence interval [CI], 0.28-0.73) and 0.21 (95% CI, 0.0-0.67), respectively., Conclusions: The combination of CPT-11, paclitaxel, and carboplatin can be safely administered and is active in the treatment of advanced NSCLC. Based on the favorable survival outcome, this regimen is undergoing evaluation in prospective randomized trials., (Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10852)

Background: The prognosis of patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is extremely poor. The aim of this study was to elucidate the efficacy of hepatic arterial infusion chemotherapy (HAIC) for patients with advanced HCCs., Methods: Forty-eight HCC patients with PVTT were treated by HAIC via a subcutaneously implanted injection port. Of these, 14 had PVTT in the second portal branch and 34 patients had PVTT in the first portal branch or in the main portal trunk. One course of chemotherapy consisted of daily cisplatin (7 mg/m(2) for 1 hour on Days 1-5) followed by 5-fluorouracil (170 mg/m(2) for 5 hours on Days 1-5). Patients were scheduled to receive four serial courses of HAIC. Responders were defined as having either a complete response (CR) or partial response (PR) and nonresponders were defined as exhibiting stable disease or progressive disease. The prognosis after HAIC and factors related to survival were analyzed., Results: Following HAIC, 4 and 19 patients exhibited a CR and PR, respectively (response rate = 48%). The 1, 2, 3, and 5-year cumulative survival rates of 48 patients treated with HAIC were 45%, 31%, 25%, and 11%, respectively. Median survival periods for 23 responders and 25 nonresponders were 31.6 (range, 8.3-76.9) months and 5.4 (1.9-29.0) months, respectively. Therapeutic effect (P < 0.001) and hepatic reserve capacity (P = 0.021) were identified as significant prognostic factors by univariate analysis. Multivariate analysis identified only therapeutic effect as being significantly related to survival., Conclusions: HAIC using low-dose cisplatin and 5-fluorouracil may be a useful therapeutic option for patients with advanced HCC with PVTT. HCC patients with PVTT who respond to HAIC could certainly have survival benefits., (Copyright 2002 American Cancer Society.)

Background: Irinotecan is effective in patients with advanced colorectal carcinoma in both first-line and salvage settings but its use can be limited by serious side effects. Amifostine has been shown to reduce the incidence of cisplatin-induced cumulative renal toxicity in patients with advanced ovarian carcinoma and nonsmall cell lung carcinoma. In the current pilot Phase II trial, the authors examined the potential role of amifostine as a protective agent against irinotecan-induced diarrhea and myelosuppression and evaluated an every-2-weeks regimen as an alternative schedule for the administration of irinotecan in patients with previously treated metastatic colorectal carcinoma., Methods: All patients received amifostine, 740 mg/m2, followed by irinotecan, 250 mg/m2, every 2 weeks. A 6-week cycle of chemotherapy (every 2 weeks for 3 treatments) was chosen to assess toxicity and response. The main objective of the current study was to evaluate the impact of amifostine on gastrointestinal and hematologic toxicity., Results: A total of 22 patients entered the current study. Six of these 22 patients (27%) had WHO Common Toxicity Criteria Grade 3 or 4 diarrhea, including 2 patients (9%) with Grade 4 diarrhea. Eight of 22 patients (36.3%) developed Grade 3 or 4 neutropenia (Grade 4 in 4 of the 22 patients [18%]). Dose reduction was required in 25% of the treatment cycles. Five of the 22 patients (23%) withdrew from the trial due to amifostine toxicity. Of the 15 patients who were evaluable for response, 4 patients (26.6%) had achieved a partial response and 9 (60%) had stable disease as their best response., Conclusions: The combination of irinotecan with amifostine in patients with previously treated metastatic colorectal carcinoma did not appear to reduce irinotecan toxicity. Amifostine did not appear to interfere with the cytotoxic effect of irinotecan. The results of the current study did demonstrate efficacy and safety of the every-2-weeks irinotecan schedule that was comparable to other established regimens and these results support its feasibility as a reasonable alternative in this disease setting., (Copyright 2002 American Cancer Society.)

Background: Bone metastases typically are associated with osteolytic bone destruction, resulting in bone pain, pathologic fractures, spinal cord compression, and hypercalcemia. Bisphosphonates are potent inhibitors of normal and pathologic bone resorption and represent a significant therapeutic improvement in the management of patients with lytic bone metastases. Zoledronic acid is a new-generation, highly potent, nitrogen-containing bisphosphonate that to the authors knowledge is the most potent inhibitor of bone resorption currently in clinical trials. The objectives of the current study were to assess the safety and tolerability of increasing doses of zoledronic acid and to determine its activity with respect to reducing biochemical markers of bone resorption in cancer patients with bone metastases., Methods: Forty-four cancer patients with bone metastases or primary bone lesions were enrolled sequentially into 1 of 5 fixed ascending-dose treatment groups. Each patient received a single intravenous bolus injection of 1, 2, 4, 8, or 16 mg of zoledronic acid over 30-60 seconds. Patients were monitored for 8 weeks for the evaluation of clinical findings, adverse events, vital signs, electrocardiograms, markers of bone resorption, and urinary N-acetyl-beta-D-glucosaminidase., Results: Zoledronic acid was safe and well tolerated at all dose levels tested. Commonly reported adverse events included bone pain, fever, anorexia, constipation, and nausea, which were experienced by a similar proportion of patients in each treatment group. Seven patients reported serious adverse events, none of which appeared to be related to the study drug. Zoledronic acid effectively suppressed biochemical markers of bone resorption, including the highly specific markers N-telopeptide and deoxypyridinoline, for up to 8 weeks in the 2-16-mg dose groups and for a shorter duration in the 1-mg group., Conclusions: In the current study, zoledronic acid was safe and well tolerated and demonstrated potent inhibition of bone resorption. The authors believe it may improve the treatment of metastatic bone disease., (Copyright 2001 American Cancer Society.)

Background: Advanced hepatocellular carcinoma has a poor prognosis. In a Phase II clinical trial, two academic centers assessed irinotecan, a topoisomerase-1 inhibitor with broad spectrum clinical activity, in patients who had advanced hepatocellular cancer., Methods: Patients who had had up to one prior chemotherapy regimen were eligible. Bidimensionally measurable disease, a good performance status, and adequate major organ function were required. At a starting dose of 125 mg/m2, irinotecan was administered weekly for 4 weeks followed by a 2 week break, which constituted 1 treatment cycle. Patients were restaged radiologically after two cycles of therapy. Dose attenuations were made as indicated for toxicity., Results: Fourteen patients were enrolled over a 10-week period in 1997. There were ten males and four females. The median age was 58 years (range, 38-74 yrs). The Eastern Cooperative Oncology Group median performance status was 1 (range, 0-1). Two patients had prior chemotherapy (14%), and 1 patient (7%) had had radiation. A total of 30 cycles of therapy were delivered (median, 1; range, 1-6). Considerable toxicity was observed, mostly neutropenia, diarrhea, nausea, vomiting, and fatigue. All patients required at least one dose attenuation for toxicity. One partial response (7%; confidence interval, 0-20%) was noted to last 7 months. One patient had transient stable disease, and all others (86%) had progression of disease as their best response., Conclusions: Irinotecan had modest activity in advanced hepatocellular cancer. Toxicity was substantial, presumably reflecting impaired underlying liver function or poor ability to metabolize and eliminate the drug. The current study indicated that continued new therapy assessment is warranted for this disease., (Copyright 2001 American Cancer Society.)

Background: The long term survival and toxicity associated with the chemotherapy combination of paclitaxel, carboplatin, and extended-schedule etoposide used for the treatment of patients with metastatic carcinoma of unknown primary site were evaluated., Methods: Seventy-one patients were treated between March 1995 and November 1996 with paclitaxel, carboplatin, and oral etoposide every 21 days. Stable or responding patients received four to eight courses of therapy. The following histologies were represented: well differentiated adenocarcinoma (34 patients); poorly differentiated adenocarcinoma or poorly differentiated carcinoma (30 patients); poorly differentiated neuroendocrine carcinoma (6 patients); and squamous cell carcinoma (1 patient)., Results: Forty-eight percent of assessable patients had major responses to therapy (95% confidence interval, 39%-55%), and 10 patients (15%) had complete responses. There were no response differences among the major histologic types. The median survival for all 71 patients was 11 months, and the 1-year, 2-year, and 3-year survival rates were 48%, 20%, and 14%, respectively. The minimum follow-up period was 34 months (range, 34-50 mos). The regimen was tolerated well with no treatment-related deaths and only 12 hospitalizations for neutropenia and fever. There was no serious long term toxicity., Conclusions: In this large Phase II trial, the combination of paclitaxel, carboplatin, and oral etoposide produced major responses or stable disease status in nearly 80% of patients who had carcinoma of unknown primary site. The median survival and 1-year, 2-year, and 3-year survival rates were noteworthy. The current study obtained similar or superior results to those seen with chemotherapy for many other groups of patients, such as those who had well defined advanced malignancies, those who were considered to have responsive tumors, and those who had obtained substantial benefits from cytotoxic therapy. Although the regimen reported in the current study can become an attractive option for many patients with carcinoma of unknown primary site, there remains a need for further clinical trials., (Copyright 2000 American Cancer Society.)

Background: In a previous study, the authors tested the combination of fotemustine (FM) 100 mg/m(2) intravenously (i.v.) on Day 1, dacarbazine (DTIC) 250 mg/m(2) i.v. on Days 2-5, and interferon alpha (IFNalpha) 3 MIU intramuscularly three times per week in 43 patients with advanced melanoma. An overall response rate of 40% and a median survival of 40 weeks were obtained. To evaluate whether the addition of cisplatin (CDDP) to this regimen could improve these results, the authors conducted a preliminary Phase I study and concluded that CDDP 25 mg/m(2) i.v. for 2 days can be combined safely with DTIC, FM, and IFNalpha. Herein, the authors report the results of a Phase II trial with this regimen., Methods: From June 1996 to February 1999, 64 patients with metastatic melanoma who were not amenable to surgery were enrolled in this study. Sixty eligible patients (32 males and 28 females; median age, 53 years) were treated with a combination of FM 100 mg/m(2) i.v. on Day 1, DTIC 300 mg/m(2) i.v. on Days 2-4, and CDDP 25 mg/m(2) i.v. on Days 3 and 4 recycled every 3 weeks. IFN alpha2b was administered at a dose of 3 MIU intramuscularly 3 times per week until disease progression., Results: A total of 189 courses were administered, with a median number of 3 courses per patient (range, 1-8 courses per patient). Eleven complete responses and 12 partial responses were observed, for an overall response rate of 38.3% (95% exact confidence interval, 26.1-51.8%). The median survival was 36 weeks. Neutropenia and thrombocytopenia affected 85% of patients and 68% patients and was World Health Organization Grade 3-4 in 40% and 50%, respectively. The side effects attributable to IFN alpha2b were mild and manageable. The other side effects were moderate and well controlled by supportive therapy., Conclusions: The schedule used in this study demonstrated significant activity in patients with advanced, untreated melanoma. The addition of CDDP in the management of the patients in this series seemed to increase significantly both the proportion of patients who achieved a complete response and the probability of long term survival compared with a previous series of patients who were treated by the authors. However, considering the currently available therapies, this regimen does not seem to offer a special advantage in the treatment of patients with this disease. New agents and new protocols are needed., (Copyright 2000 American Cancer Society.)

Background: Cisplatin-based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease., Methods: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty-five consecutive chemotherapy-naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of paclitaxel (135 mg/m(2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg/m(2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second-line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given., Results: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73.5% of the patients (95% confidence interval [CI], 55.6-87.1%), including 4 complete responses (11.7%). According to intention-to-treat, the overall response rate was 71.4% (95% CI, 53. 7-85.4%). After 154 courses of therapy, the median dose intensity was 131 mg/m(2) for paclitaxel (97.3%), 117 mg/m(2) for cisplatin (97.3%), and 1378 mg/m(2) for gemcitabine (86.2%). World Health Organization Grade 3-4 neutropenia and thrombocytopenia occurred in 39.9% and 11.4% of patients, respectively. There was one treatment-related death. Nonhematologic toxicities were mild. After a median follow-up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months., Conclusions: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin-based regimens., (Copyright 2000 American Cancer Society.)

Background: Although 5-HT3 receptor antagonists are clinically more effective in controlling emesis, particularly that caused by high dose cisplatin, than previously available agents, they appear to be less effective against nausea. This report focuses on the effectiveness of these agents against nausea and emesis in patients receiving two moderately emetogenic combination chemotherapy regimens as treatment for breast carcinoma in community practice settings., Methods: Six hundred ninety-two breast carcinoma patients (688 female, 4 male; mean age, 51 years) enrolled in a nonrandomized study completed the Morrow Assessment of Nausea and Emesis (MANE) following 4 consecutive chemotherapy treatments. The frequency, duration, and severity of postchemotherapy nausea (PN) and postchemotherapy emesis (PE) were compared by type of antiemetic (5-HT3 receptor antagonist vs. other) and chemotherapy regimen (cyclophosphamide and doxorubicin with or without 5-fluorouracil [CA/CAF] vs. cyclophosphamide, methrotrexate, and 5-fluorouracil [CMF])., Results: Within each regimen, the mean duration of PN was significantly longer for patients who received a 5-HT3 receptor antagonist than for those who were not given an antiemetic of that type (CA: 40.3 hours vs. 29.6 hours, P < 0.05; CMF: 37.6 hours vs. 30.2 hours, P < 0.05). There were no significant differences in the frequency or severity of nausea or in the frequency, severity, or duration of emesis by type of antiemetic for patients receiving either regimen., Conclusions: The results of this observational study suggest that 5-HT3 receptor antagonists are no more effective than other commonly used medications in controlling postchemotherapy nausea and emesis in women with breast carcinoma who are treated with moderately emetogenic chemotherapy in community practice settings. In fact, they may be associated with significant prolongation of the course of postchemotherapy nausea.

Background: This multicenter, Phase II trial was performed to evaluate the antitumor activity and toxicity of irinotecan (CPT-11) in patients with metastatic colorectal carcinoma that had recurred or progressed after 5-fluorouracil (5-FU)-based chemotherapy., Methods: CPT-11 was given as a 90-minute intravenous infusion in repeated 6-week (42-day) courses comprising weekly treatment for 4 consecutive weeks followed by a 2-week rest. Tumor measurements were obtained after every second course of therapy. Toxicity was assessed weekly using the National Cancer Institute Common Toxicity Criteria., Results: A total of 166 patients were entered into the trial. The first 64 patients received a starting dose of 125 mg/m2. An additional 102 patients were enrolled at a starting dose of 100 mg/m2 to determine whether a reduction in the starting dose would result in lower toxicity without sacrificing efficacy. Objective responses to CPT-11 were observed in 18 patients (1 complete response and 17 partial responses) (response rate [RR] = 10.8%; 95% confidence interval [CI], 6.1-15.6%). An additional 67 patients (40.4%) had stable disease as their best response. At the 125 mg/m2 starting dose, the RR was 14.1% (9 of 64 patients; 95% CI, 5.5-22.6%). Among patients given a starting dose of 100 mg/m2, the RR was 8.8% (9 of 102 patients; 95% CI, 3.3-14.3%). The overall median survival was 9.9 months (range, 0.3-36.8 months). The most frequently observed Grade 3/4 toxicities were gastrointestinal events (i.e., diarrhea [27.1%], nausea [15.1%], emesis [9.6%], abdominal cramping [22.2%], and neutropenia [19.9%]). There were no significant differences in the frequencies of Grade 3/4 toxicities between the 125 mg/m2 and 100 mg/m2 starting dose levels except for Grade 3/4 emesis (21.9% vs. 2%; P < 0.001). Patients age > or = 65 years were twice as likely (38.6% vs. 18.8%; P < 0.008) to develop Grade 3/4 diarrhea compared with younger patients when all courses of therapy were evaluated. However, older age did not significantly predict for a higher incidence of first-course diarrhea (25.0% vs. 14.7%; P = 0.106)., Conclusions: CPT-11 can induce tumor regression in patients with metastatic colorectal carcinoma that has progressed during or shortly after 5-FU-based chemotherapy. Gastrointestinal events and neutropenia were the most common serious toxicities. Given the trend toward a higher response rate without substantially greater toxicity, 125 mg/m2 has been selected as the preferred starting dose for further studies. Careful attention to appropriate CPT-11 dose modification and early intervention with loperamide may be especially important in elderly patients.

Background: Chemotherapy-induced emesis is one of the most disturbing side effects of cancer therapy. Control of acute emesis has improved substantially during recent years, but control of delayed emesis and nausea remains a challenging problem. The role of 5-HT3 receptor antagonists in the treatment of delayed emesis is disputed., Methods: Tropisetron, a highly specific 5-HT3 receptor antagonist, was compared (as an adjunct to dexamethasone) with placebo in a randomized, double blind, multicenter trial for the prevention of delayed emesis during platinum-containing chemotherapy. Three hundred chemotherapy-naive women with gynecologic malignancies were included. The cisplatin dose was in the range of 50-100 mg/m2., Results: Acute emesis was prevented completely in 87% of patients and acute nausea in 77% of patients in the complete series. During the complete delayed period (Days 2-6), total control of emesis was achieved in 77% of the dexamethasone and tropisetron-treated patients and in 72% of the patients receiving dexamethasone and placebo (P = 0.2473). During the same period nausea was controlled completely in 42% of the dexamethasone and tropisetron group and in 41% of the dexamethasone and placebo group. On Day 3, complete protection from nausea was achieved in 65% of patients receiving tropisetron and in 51% of patients receiving placebo (P = 0.0304). Constipation occurred more frequently in the tropisetron group., Conclusions: Tropisetron added to dexamethasone improved control of delayed nausea on Day 3 compared with placebo. No significant differences were recorded regarding control of delayed emesis.

Background: The combination of cisplatin, ifosfamide, and prolonged oral etoposide (PIE) was studied in patients with extensive small cell lung carcinoma (SCLC) in a Phase I trial followed by a Phase II trial to determine the maximum tolerated dose (MTD), characterize toxicity, and estimate response and median survival rates., Methods: Thirty-three patients were treated between October 1991 and December 1994. Doses for the initial cohort were cisplatin 20 mg/m2/day, ifosfamide 1500 mg/m2/day with mesna (all given intravenously on Days 1-3), and oral etoposide 50 mg/m2 on Days 4-17. This cycle was repeated every 4 weeks for up to 6 cycles. The MTD was reached for the first 9 patients. For these 9 patients and the next 24 patients, who were entered in the Phase II trial, response and survival were estimated., Results: Dose-limiting toxicity was manifested as Grade 4 neutropenia in 3 of 3 patients (associated with fever in 2 of 3), and Grade 4 thrombocytopenia was encountered in 2 of 3 patients at the second dose level. Of 6 patients treated at the first dose level, 4 achieved targeted myelosuppression (absolute granulocyte count nadir <1000), but only 1 experienced Grade 4 neutropenia, defining this level as the MTD. Grade 4 neutropenia and/or thrombocytopenia was observed in 36 (24%) of a total of 152 courses administered at or below the MTD. Nonhematologic toxicity above Grade 2 was uncommon, excluding nausea and vomiting. Overall objective response rate was 93% of 30 evaluable patients: 5 (17%) complete responses and 23 partial responses (76%). Median failure free and overall survival durations were 36 and 54 weeks, respectively., Conclusions: The combination of cisplatin, ifosfamide, and oral etoposide produced encouraging failure free and overall median survival rates in patients with extensive SCLC. These results warrant further evaluation of this regimen in the initial therapy of patients with limited stage disease.

Background: The aim of this study was to determine the efficacy of novobiocin and rifampin as oral antibiotic prophylaxis for the prevention of catheter-related infection in melanoma patients treated with interleukin-2 (IL-2) plus interferon-alpha and chemotherapy (biochemotherapy)., Methods: Patients with advanced melanoma who were treated with biochemotherapy at the University of Texas M. D. Anderson Cancer Center were randomized in a crossover study to receive either oral antibiotic prophylaxis consisting of novobiocin and rifampin or observation alone over a 35-day course period. Patients were subsequently "crossed over" to the opposite arm of the study for an additional 35-day period, with each serving as his or her own control., Results: Twenty-six patients were enrolled. Nine patients (35%) failed to tolerate oral antibiotics because of severe nausea and vomiting; 17 patients (65%) were crossed over and considered evaluable. During the control patient courses, 71% of evaluable patients had infectious complications, 41% had a catheter-associated bacteremia, and 53% had a local catheter infection. In contrast, of the patients treated with antibiotic prophylaxis, only 12% had an infectious complication (P = 0.001), 12% had a local catheter infection (P = 0.008), and 6% had catheter-associated bacteremias (P = 0.04). Thirty-six episodes of catheter infections occurred during the 17 control courses, whereas only 3 episodes occurred during antibiotic prophylaxis (P < 0.001)., Conclusions: Although more than one-third of patients receiving IL-2 treatment with biochemotherapy failed to tolerate novobiocin and rifampin, this oral antibiotic regimen was efficacious in preventing the infectious complications, especially those associated with vascular catheters, in this high risk patient population.