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Background Docetaxel (DOC) and abiraterone (ABI) in the upfront setting have separately improved clinical outcomes for metastatic hormone-sensitive prostate cancer (mHSPC), but there are no studies comparing drug efficacies or the influence of racial disparities. Materials and Methods We performed a retrospective multicenter review from Winship Cancer Institute at Emory University and Georgia Cancer Center for Excellence at Grady Memorial Hospital (2014–2020) for patients with mHSPC treated with either upfront DOC or ABI. Outcomes evaluated were overall survival (OS), progression-free survival (PFS), and prostate-specific antigen complete response (PSA CR). Results A total of 168 patients were included, consisting of 92 (54.8%) Black patients and 76 (45.2%) non-Black patients (69 White and 7 Asian or Hispanic). Ninety-four (56%) received DOC and 74 (44%) received ABI. Median follow-up time was 22.8 months with data last reviewed June 2020. For OS, there was no significant difference between ABI versus DOC and Black versus non-Black patients. For PFS, DOC was associated with hazard ratio (HR) 1.7 compared with ABI for all patients based on univariate association and HR 2.27 compared with ABI for Black patients on multivariable analysis. For PSA CR, Black patients were less likely to have a CR (odds ratio [OR] = 0.27). Conclusion ABI and DOC have similar OS with a trend toward better PFS for ABI in a cohort composed of 54% Black patients. Racial disparities were observed as prolonged PFS for Black patients treated with ABI, more so compared with all patients, and less PSA CR for Black patients. A prospective trial comparing available upfront therapies in a diverse racial population is needed to help guide clinical decision-making in the era of novel treatment options. Implications for Practice Overall survival is similar for abiraterone and docetaxel when used as upfront therapy in metastatic hormone-sensitive prostate cancer in a cohort composed of 54% Black patients. There is a trend towards improved progression-free survival for abiraterone in all patients and Black patients. Non-Black patients were more likely to achieve prostate-specific antigen (PSA) complete response regardless of upfront therapy.

52 Background: The landscape of mCSPC treatment changed with the addition of ABA and DOC. The prevalence of AA pts in the trials that led to these approvals was < 10%. We characterized the clinical outcomes (CO) of a cohort of AA pts treated with these agents. Methods: We retrospectively reviewed 51 AA pts with mCSPC treated with ABA or DOC at Grady Memorial Hospital from 2015-2018. The CO included median overall survival (mOS), progression-free survival (mPFS) and PSA response (PSAr) as defined by a ≥ 50% drop in PSA over the 1st 12 weeks of treatment. Cox proportional hazard model and Kaplan-Meier method were used for association with OS and PFS and logistic regression model for PSAr. Results: Median age was 63 years, 64% were grade group 5 and 67% had an ECOG status of 0-1. 82% had high volume disease per CHAARTED; 51% did per LATITUDE. 21 pts received ABA; 30 received DOC. The groups (ABA vs DOC) were balanced except for high volume disease per LATITUDE (28.6 vs. 66.7%) and lymph node metastases (66.7 vs. 96.7%). The DOC cohort received a mean of 5.2 cycles. Median follow-up was 10.3 months (mos). The overall mOS was 37.8 mos, mPFS was 10.3 mos, and PSAr was 89.6%. CO trended toward favoring ABA over DOC but did not differ significantly with a 12-month OS of 100% vs. 81.7% and PFS of 53.7% vs. 35.4%, respectively. Albumin and hemoglobin at baseline were associated with CO (Table). Conclusions: We present the first real world efficacy of ABA and DOC in a cohort of AA pts with mCSPC and found similar outcomes between the two groups. These findings warrant a larger study for validation.[Table: see text]

51 Background: AA pts represented < 3% of the COU-AA-302 and PREVAIL trial cohorts that led to the approval of ABA and ENZ in the 1st line treatment of mCRPC. We characterized the clinical outcomes (CO) and developed a risk score for AA pts with mCRPC on these agents. Methods: We retrospectively reviewed 77 AA pts with mCRPC treated with 1st line ABA or ENZ at Grady Memorial Hospital from 2015-2018. The CO included median overall survival (mOS), progression-free survival (mPFS) and PSA response (PSAr) as defined by a ≥ 50% drop in PSA over the 1st 12 weeks of treatment. Cox proportional hazard model and Kaplan-Meier method were used for association with OS and PFS and logistic regression model for PSAr. The risk score was built by regression coefficient-based scoring system using OS as the 1° outcome. Covariates included grade group (GG), baseline (bl) PSA, albumin, and BMI, ECOG status, and age. Results: Median age was 60 years with median follow-up of 11.5 months (mos). 50 pts received ABA; 27 received ENZ. The overall mOS was 45.7 mos, mPFS was 12.9 mos, and PSAr was 84.4%. CO did not differ significantly for ABA vs. ENZ with a 24-month OS of 66.6% vs. 57.7% and PFS of 34.3% vs. 45%. 1 point was assigned for each of the following: GG > 3, bl PSA ≥ 108, or bl albumin ≤ 4.2. The total was classified into low (0-1), intermediate (2), and high (3) risk and associated with CO via univariate (UVA) and multivariate (MVA) analyses (Table). Conclusions: We present the efficacy of ABA and ENZ in a cohort of AA pts with mCRPC. Risk grouping using bl PSA, bl albumin and GG may predict CO in this population. These results should be validated in a larger, prospective study.[Table: see text]

BACKGROUND Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60–120 mg/m2 of cisplatin is administered every 3–4 weeks. Although a dose–response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial. Cancer 2001;92:2517–22. © 2001 American Cancer Society.

To compare the effectiveness and safety of controlled-release (CR) oxycodone tablets with immediate-release (IR) oxycodone in patients with chronic cancer pain, a multicenter, randomized, double-blind, parallel-group study was performed in 111 patients with cancer pain. Patients were treated with 6 to 12 tablets or capsules of fixed-combination opioid/nonopioid analgesics per day at study entry. Patients received 30 mg of CR oxycodone tablets every 12 hr or 15 mg of IR oxycodone four times daily for 5 days. No titration or supplemental analgesic medications were permitted. The mean (+/- SE) baseline pain intensity (0 = none, 1 = slight, 2 = moderate, 3 = severe) was 1.5 +/- 0.1 for the CR oxycodone-treated group and 1.3 +/- 0.1 for the group given IR oxycodone (P > 0.05). The 5-day mean pain intensity was 1.4 +/- 0.1 and 1.1 +/- 0.1 for the CR and IR groups, respectively (P > 0.05). Discontinuation rates were equivalent (33%). There was no significant difference between treatment groups in the incidence of adverse events. This study demonstrates that cancer pain patients given 6 to 12 tablets or capsules of fixed-dose combination analgesics can be equally well treated with CR oxycodone administered every 12 hr or IR oxycodone four times daily at the same total daily dose. CR oxycodone offers the benefits of twice daily dosing.

To measure the prevalence of current drinking and potential problem drinking in an inner-city ambulatory care setting, using the CAGE questionnaire.Survey of patients attending ambulatory care clinics, using structured personal interviews.Three ambulatory care clinics serving an indigent, predominantly black population of metropolitan Atlanta: a general medical appointment clinic, a walk-in clinic, and a neighborhood primary care clinic.Patients over the age of 18 who attended one of the above clinics on a day when interviewers were available and who were estimated to have more than a 45-minute wait prior to seeing their health provider.None.15.3% of subjects had CAGE scores greater than or equal to 2 (95% CI 12.2, 19.0). A CAGE score of greater than or equal to 2 was almost three times more common in men than in women, 26.7% vs. 9.5%. Only 8.6% (95% CI 6.3, 11.7) of subjects reported drinking greater than or equal to 2 drinks per day. These findings suggest that problem drinking may affect as many as one in six people seeking care in inner-city ambulatory care clinics and provide support for the use of screening instruments such as the CAGE questionnaire for improved sensitivity in detecting alcoholism in these practice settings.

For patients whose breast cancers are not responsive to endocrine therapy, there are a large number of cytotoxic drugs that will induce a response. In spite of the introduction of new, very active drugs such as the taxanes, vinorelbine, capecitabine, gemcitabine, and trastuzumab, the anthracyclines are still as active as any--and more active than most--drugs used to treat breast cancer. Their inclusion in combinations to treat early and advanced disease prolongs survival. However, they cause nausea, vomiting, alopecia, myelosuppression, mucositis, and cardiomyopathies. There is no evidence that increasing the dose of conventional anthracyclines or any other of the cytotoxics beyond standard doses will improve outcomes. Schedule may be more important than dose in determining the benefit of cytotoxics used to treat breast cancer. Weekly schedules and continuous infusions of 5-fluorouracil and doxorubicin may have some advantages over more intermittent schedules. Liposomal formations of doxorubicin reduce toxicity, including cardiotoxicity; theoretically they should also be more effective because of better targeting of tumor over normal tissues. Both pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]) and liposomal doxorubicin (Myocet [NPLD]) appeared to be as effective as conventional doxorubicin and much less toxic in multiple phase II and phase III studies. PLD has been evaluated in combinations with cyclophosphamide, the taxanes, vinorelbine, gemcitabine, and trastuzumab, and NPLD has been evaluated in combination with cyclophosphamide and trastuzumab. Both liposomal anthracyclines are less cardiotoxic than conventional doxorubicin. The optimal dose of PLD is lower than that of conventional doxorubicin or NPLD. Patients treated with PLD have almost no alopecia, nausea, or vomiting, but its use is associated with stomatitis and hand-foot syndrome, which can be avoided or minimized with the use of proper dose-schedules. In contrast, the optimal dose-schedule of NPLD is nearly identical to that of conventional doxorubicin. The toxicity profile of NPLD is similar to that of conventional doxorubicin, but toxicities are less severe and NPLD is better tolerated than conventional doxorubicin at higher doses.

Purpose: Randomized trials in fluorouracil (FU)-refractory colorectal cancer demonstrate significant survival advantages for patients receiving irinotecan. We prospectively compared the efficacy and tolerability of two irinotecan regimens (once a week for 4 weeks followed by a 2-week rest period [weekly] v once every 3 weeks) in such patients. Patients and Methods: This multicenter, open-label, phase III study randomly assigned patients in a 1:2 ratio to irinotecan given either weekly (125 mg/m2) or once every 3 weeks (350 mg/m2, or 300 mg/m2 in patients who were ≥ 70 years of age, who had Eastern Cooperative Oncology Group performance status equal to 2, or who had prior pelvic irradiation). Results: With median follow-up of 15.8 months, there was no significant difference in 1-year survival (46% v 41%, respectively; P = .42), median survival (9.9 v 9.9 months, respectively; P = .43), or median time to progression (4.0 v 3.0 months, respectively; P = .54) between the two regimens. Grade 3/4 diarrhea occurred in 36% of patients treated weekly and in 19% of those treated once every 3 weeks (P = .002). Grade 3/4 neutropenia occurred in 29% of patients treated weekly and 34% of those treated once every 3 weeks (P = .35). Treatment-related mortality occurred in five patients (5.3%) receiving irinotecan weekly and three patients (1.6%) given therapy once every 3 weeks (P = .12). Global quality of life was not statistically different between treatment groups. Conclusion: Irinotecan schedules of weekly and of once every 3 weeks demonstrated similar efficacy and quality of life in patients with FU-refractory, metastatic colorectal cancer. The regimen of once every 3 weeks was associated with a significantly lower incidence of severe diarrhea.

In a prospective study of 622 women with breast cancer, those with one to three histologically positive axillary lymph nodes were randomised after mastectomy to receive cyclophosphamide 100 mg/m2 orally on days 1-14, methotrexate 40 mg/m2 intravenously on days 1 and 8, and fluorouracil 600 mg/m2 intravenously on days 1 and 8 every 28 days for six cycles (CMF x six), or for twelve cycles of the same chemotherapy (CMF x 12). Those with > or = four positive nodes were randomised to one of these two groups or to 5000 cGy of postmastectomy regional radiotherapy (RT) followed by six cycles of the same chemotherapy (RT + CMF x six). With about 10 years median follow-up, there was no significant difference in survival or disease-free survival among the three groups. There was evidence of decreased locoregional recurrence in patients with > or = four nodes who received RT + CMF x six (relative risk 0.53, P = 0.067). Multivariate analysis indicated that the presence of > or = four positive nodes (negatively) and the percentage of ideal (full) dose of CMF received (positively) were the strongest factors predictive of survival. This study shows no advantage for 12 over six cycles of CMF chemotherapy in women with breast cancer and positive axillary nodes. There was a suggestion of decreased locoregional recurrence but no improvement in survival with radiotherapy for women with > or = four positive nodes.

Patients with visceral patterns of metastatic breast cancer were stratified according to dominant metastatic site and performance status and then randomized to therapy with cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) or CAF alternating with a "cell-cycle active" regimen including cytosine arabinoside, methotrexate with leucovorin rescue, and oncovin ( CAMELEON ). One hundred eighty-seven patients were randomized; response rate for CAF was 44% and for CAF + CAMELEON , 40%. Durations of disease control and survival were not significantly different. Toxicity of CAF was as anticipated with predominant granulocytopenia, vomiting, and alopecia. Toxicity of CAMELEON was less severe than that of CAF, and CAF toxicity was not worsened by preceding courses of CAMELEON ; however, the CAF- CAMELEON regimen was cumbersome and complex leading to both physician and patient noncompliance. Contrary to the preliminary results of a pilot study, and preliminary reports of the present trial suggesting benefit for the CAF- CAMELEON regimen the present randomized trial does not confirm any significant benefit of CAF- CAMELEON over CAF alone in patients with visceral metastatic breast cancer although this conclusion must be viewed in light of the high inevaluability rate due to patient and physician noncompliance.

We analyzed the case histories of 31 patients who initially had a diagnosis of seminoma and elevated serum levels of alpha-fetoprotein or human chorionic gonadotropin. We concluded that an elevated alpha-fetoprotein level is firm evidence of the presence of non-seminomatous germ cell tumor and that the patient should be treated accordingly. However, if the level of human chorionic gonadotropin alone is elevated the diagnosis may be either non-seminomatous tumor or seminoma. Patients with seminoma and an elevated level of human chorionic gonadotropin do respond well to radiation therapy if they have low stage disease but if metastatic seminoma is present an elevated human chorionic gonadotropin level appears to be a poor prognostic sign if conventional treatment is given. A plan of treatment is proposed for these patients.

Eighty-one patients with advanced active Hodgkin's disease began treatment with MOPP combination chemotherapy. No patients were excluded from analysis. Twenty-one patients (26%) were induction failures and manifested a median survival of 9 months from the initiation of treatment. Sixty patients (74%) achieved a complete remission (CR) with an estimated median duration of CR of 26 months. Seventeen patients relapsed and 14 of these occurred during the first 6 months of follow-up. Reinduction with MOPP in this group was unsuccessful in eight of eight instances. Prior radiotherapy (60 cases) and prior chemotherapy (21 cases) did not adversely affect the results of treatment. However, a decreased duration of remission correlated with older age, the presence of systemic symptoms, and bone marrow involvement.

Three cases of hypersensitivity to oral procarbazine (Matulane®) are described. All occurred during 4-drug combination chemotherapy of Hodgkin's disease. Two reactions primarily involved the skin. The third patient manifested recurrent fever, pulmonary infiltration, pleural effusion, and eosinophilia ultimately demonstrated to be secondary to procarbazine on controlled challenge. The pertinent literature is reviewed.

Between September 1976 and June 1982, 308 patients with operable breast cancer with 1–3 involved axillary nodes were stratified according to institution, type of mastectomy, and time from surgery to protocol entry, and then randomized to receive either six or 12 months of adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). With a median time of follow-up of 33 months, relapse rates among 181 reviewed and evaluable patients are 20/85 (23.5%) for pre- and 23/96 (24%) for postmenopausal patients. Results for premenopausal women, while better than historical controls at a similar time interval, appear inferior to other published adjuvant studies (e.g., NSABP and Milan). Although total relapse rates were 23/100 (23%) for six months and 20/81 (25%) for 12 months of therapy, suggestive differences were encountered by menopausal status with early trends favoring 12 months of treatment for premenopausal patients and six months of treatment for postmenopausal patients. During this same period, 283 patients with four or more involved axillary nodes were randomized to 1–3 treatment arms: six months of CMF, six months of CMF preceded by local-regional x-ray therapy (XRT), or 12 months of CMF. The latter arm was closed in February 1980 while the two six-month chemotherapy arms remain open as of January 1983. Relapse rates for 174 reviewed and evaluable patients on the three arms include: 27/76 (36%) for six months CMF, 15/54 (28%) for XRT and CMF, and 24/44 (45%) for 12 months CMF. Local-regional relapse rates were 12/120 (10%) for the combined two non-XRT arms and 3/54 (6%) for the XRT treatment arm (p = 0.34). Thus, at this early stage of follow-up there are still no statistically significant differences between six or 12 months of adjuvant CMF therapy and neither definite beneficial nor detrimental effects of prechemotherapy adjuvant radiation therapy. Longer follow-up will be needed to provide definitive conclusions.

During the past 10 years, the Southeastern Cancer Study Group (SECSG) has been engaged in one major adjuvant study and three major advanced disease studies for patients with adenocarcinoma of the breast. The adjuvant study is demonstrating that six months of adjuvant CMF is the therapeutic equivalent of 12 months and that post-operative irradiation is of no added therapeutic benefit. In patients with advanced disease, a low dose 5 drug combination of CMFVP induces more objective responses than single agent 5FU, but improves survival only for those patients with liver metastases when compared to the sequential use of the same 5 single agents. The three drug combination, CAF, utilizing doxorubicin, induces more objective responses than low dose CMFVP, but it does not improve overall survival. The subsets of patients with bone-only metastases, with local chest wall recurrence and with nodular lung metastases benefit from CAF in terms of a longer duration of disease control and longer duration of unmaintained remission, but have only a marginal improvement in survival. The addition of a phase active combination, CAMELEON, (i.e., sequentially alternating therapy) to CAF has not improved the duration of disease control and survival for patients with liver metastases, lymphangitic and nodular lung metastases compared to CAF. Aggressive combination chemotherapeutic approaches to patients with advanced disease provide better and longer disease and tumor control but only marginal improvements in overall survival. Adding additional agents to a maximally tolerable regimen has not improved the therapeutic outcome.

The medical records of 494 patients who underwent splenectomy, including 269 patients with lymphoma, were analyzed for the occurrence of postsplenectomy bacteremia. Twenty-three episodes of bacteremia were identified among patients in the nonlymphoma group, and 12 episodes in the lymphoma group. Five cases of pneumococcal bacteremia were identified, and all occurred in patients with lymphoma. The fatality rate did not differ among patients with or without lymphoma in whom bacteremia developed after splenectomy. The findings do not indicate that splenectomy alters the fatality rate in patients with serious associated disease in whom bacteremia subsequently develops.