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Introduction: Neuroendocrine carcinoma (NEC) is characterized by a poor prognosis and is generally treated with platinum and etoposide combination therapy as first-line chemotherapy. However, it remains uncertain whether carboplatin and etoposide combination therapy (CE) and cisplatin and etoposide combination therapy (PE) have comparable treatment efficacy. In this retrospective analysis, we compared the efficacy and safety of CE and PE in patients with NEC., Methods: We retrospectively reviewed the patient's clinical record from 2005 to 2022 at the Department of Medical Oncology, Tohoku University Hospital. Patients who received either CE or PE were included in the study. Statistical analyses were performed using JMP Pro 16.0 (SAS Institute Inc., Cary, NC, USA)., Results: A total of 104 patients were enrolled, with 73 patients assigned to the CE group and 31 patients assigned to the PE group. Statistically, the response rate, progression-free survival time and overall survival time were 42.6%, 5.1 months (95% CI: 3.5-6.3) and 13.6 months (95% CI: 8.9-17.4), respectively, in the CE groups and 44.4%, 5.6 months (95% CI: 3.1-7.0) and 12.5 months (95% CI: 11.2-14.6), respectively, in the PE groups. There was no significant difference in treatment efficacy between the CE and the PE groups. However, the number of patients with elevated creatinine (3.35 mg/dL and 3.88 mg/dL in 2 patients, respectively) was significantly higher in the PE group than in the CE group., Conclusion: The efficacy of CE and PE in patients with NEC is comparable. However, the incidence of renal dysfunction was found to be significantly higher in the PE group than in the CE group., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Purpose: The current study aimed to determine the efficacy of trifluridine/tipiracil for elderly patients with advanced colorectal cancer., Methods: This single-arm, open-label, multicenter, phase II study included elderly patients aged 65 years or more who had fluoropyrimidine-refractory advanced colorectal cancer and received trifluridine/tipiracil (70 mg/m 2 , days 1-5 and 8-12, every 4 weeks). The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), overall response rate (ORR), toxicities, association between efficacy and geriatric assessment scores, and association between toxicity and plasma drug concentrations., Results: A total of 30 patients with a mean age of 73 years were enrolled. Median PFS was 2.3 months (95% confidence interval, 1.9-4.3 months), while median OS was 5.7 months (95% confidence interval, 3.7-8.9 months). Patients had an ORR of 0%, with 57% having stable disease. Grade 4 neutropenia was observed in 13% of the patients. Patients with a higher G8 score (15 or more) showed longer PFS than those with a lower G8 score (median 4.6 vs. 2.0 months; p = 0.047). Moreover, patients with grade 3 or 4 neutropenia showed higher maximum trifluridine concentrations than those with grade 1 or 2 neutropenia (mean 2945 vs. 2107 ng/mL; p = 0.036)., Discussion: The current phase II trial demonstrated that trifluridine/tipiracil was an effective and well-tolerated option for elderly patients with advanced colorectal cancer. Moreover, geriatric assessment tools and/or plasma drug concentration monitoring might be helpful in predicting the efficacy and toxicities in elderly patients receiving this drug., Trial Registration Number: UMIN000017589, 15/May/2015 (The University Hospital Medical Information Network)., (© 2021. The Author(s).)

Fluorouracil (5FU) is converted to its active metabolite fluoro‑deoxyuridine monophosphate (FdUMP) through the orotate phosphoribosyl transferase (OPRT)‑ribonucleotide reductase (RR) pathway and thymidine phosphatase (TP)‑thymidine kinase (TK) pathway and inhibits thymidylate synthase (TS), leading to inhibition of thymidine monophosphate (dTMP) synthesis through a de novo pathway. We investigated the mechanism of 5FU resistance and strategies to overcome it by focusing on 5FU metabolism. Colon cancer cell lines SW48 and LS174T and 5FU‑resistant cell lines SW48/5FUR and LS174T/5FUR were used. FdUMP amount was measured by western blotting. The FdUMP synthetic pathway was investigated by combining TP inhibitor (tipiracil hydrochloride; TPI) or RR inhibitor (hydroxyurea; HU) with 5FU. Drug cytotoxicity was observed by crystal violet staining assay. FdUMP was synthesized through the OPRT‑RR pathway in SW48 cells but was scarcely synthesized through either the OPRT‑RR or TP‑TK pathway in SW48/5FUR cells. FdUMP amount in SW48/5FUR cells was reduced by 87% vs. SW48 cells. Expression levels of OPRT and TP were lower in SW48/5FUR when compared with these levels in the SW48 cells, indicating decreased synthesis of FdUMP‑led 5FU resistance. These results indicated that fluoro‑deoxyuridine (FdU) rather than 5FU promotes FdUMP synthesis and overcomes 5FU resistance. Contrastingly, FdUMP was synthesized through the OPRT‑RR and TP‑TK pathways in LS174T cells but mainly through the TP‑TK pathway in LS174T/5FUR cells. FdUMP amount was similar in LS174T/5FUR vs. the LS174T cells. OPRT and RR expression was lower and TK expression was higher in LS174T/5FUR vs. the LS174T cells, indicating that dTMP synthesis increased through the salvage pathway, thus leading to 5FU resistance. LS174T/5FUR cells also showed cross‑resistance to FdU and TS inhibitor, suggesting that nucleoside analogs such as trifluoro‑thymidine should be used to overcome 5FU resistance in these cells. 5FU metabolism and mechanisms of 5FU resistance are different in each cell line. Both synthesized FdUMP amount and FdUMP sensitivity should be considered in 5FU‑resistant cells.

Background: The safety of pembrolizumab monotherapy in treatment-naïve non-small cell lung cancer (NSCLC) patients with high programed death-ligand 1 (PD-L1) expression and pre-existing interstitial lung disease (ILD) has not yet been determined. Here, we aimed to evaluate the prognosis, efficacy and safety associated with pembrolizumab in such settings., Methods: In this single-institution retrospective study conducted from May 2017 to October 2019, pembrolizumab was administered to 72 Japanese patients with treatment-naïve advanced NSCLC with PD-L1 tumor proportion score (TPS) ≥50%. Patients with ILD were assigned to the ILD group, and those without to the non-ILD group. Between-group comparisons were then performed., Results: Of the 72 patients, 61 (84.7%) were male. The median age was 70 years. A total of 64 patients (88.9%) had a smoking history, median PD-L1 TPS status was 77.5%, and 10 of the 72 patients (13.9%) had ILD on pretreatment computed tomography. The objective response rate (ORR) was 45.8% and disease control rate (DCR) was 75.0%. The ORR was 70.0% and DCR was 90.0% in the ILD group, while the ORR was 41.9% and DCR was 72.6% in the non-ILD group. The median overall survival was 568 days; the value in the non-ILD group was 521 days, while in the ILD group was not reached. There was no significant difference between the two groups (log-lank, P = 0.73)., Conclusions: Pembrolizumab was administered to patients with pre-existing ILD with no difference in prognosis compared to patients without ILD. In patients with ILD, physicians should consider the expected long-term prognosis and risk of adverse events., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Purpose: Although docetaxel plus ramucirumab has shown superior treatment efficacy over docetaxel monotherapy for patients with non-small cell lung cancer (NSCLC), the high rate of febrile neutropenia (FN) presents a clinical problem. This study aimed to validate the primary prophylactic use of pegfilgrastim with docetaxel and ramucirumab treatment in Japanese patients with NSCLC., Methods: Patients with NSCLC with progression after at least one round of chemotherapy were enrolled and administered docetaxel (60 mg/m 2 ) plus ramucirumab (10 mg/kg) intravenously on day 1, followed by pegylated-granulocyte colony-stimulating factor (3.6 mg) on day 2 of a 21-day treatment cycle. The primary study endpoint was the percentage of patients who developed FN. Secondary endpoints included overall survival, progression-free survival, overall response rate, and safety., Results: Overall, 20 patients (15 men and 5 women) were enrolled, of whom one developed FN, resulting in an overall FN rate of 5%. The response and disease control rates were 40% and 85%, respectively. The median progression-free survival was 6.6 (95% confidence interval [CI], 0.5-NR) months. The median overall survival was 18.4 (95% CI, 2.2-11.0) months. Six patients aged over 75 years were included in this study, and although most adverse events were durable, ramucirumab-associated adverse events occurred more frequently in these patients., Conclusions: We observed a 5% FN rate using primary prophylactic pegylated-granulocyte colony-stimulating factor with docetaxel plus ramucirumab in Japanese patients with NSCLC. While most adverse events were durable, elderly patients should be closely monitored.

Vincristine (VCR)-induced peripheral neuropathy (VIPN) is a common and life-long toxicity in lymphoma patients receiving current standard chemotherapy. The association between VIPN and genetic polymorphisms is largely unknown in adult lymphoma patients. To examine the possible relationship between known genetic polymorphisms in patients with pediatric acute lymphoblastic leukemia and incidence of VIPN in adult patients with B cell lymphoma, we examined CEP72 rs924607, ETAA1 rs17032980, MTNR1B rs12786200, CYP3A5 rs776746, rs7963521, and rs1045644 genetic polymorphisms in samples from 56 adult patients with B-cell lymphoma who received rituximab, cyclophosphamide, doxorubicin, VCR, and prednisone (R-CHOP) chemotherapy. Mutation analysis was performed by direct sequencing. The median age was 65 years (range 30-79). The median cumulative dose of VCR was 12 mg (range 2-16). VIPN was documented in 42 patients (75%), and 9 (16%) had grade 2-4 VIPN. Age, impaired glucose tolerance, number of cycles of R-CHOP, and VCR cumulative dose were not associated with incidence of VIPN. There was no association between the incidence of grade 2-4 or any grade VIPN and these six genetic polymorphisms. These results indicate that CEP72, MTNR1B, ETAA1, CYP3A5, rs7963521, and rs1045644 genetic polymorphisms are not associated with VIPN in patients with B-cell lymphoma who received R-CHOP.

Purpose: Combination carboplatin and S-1 is active in the treatment of non-small cell lung cancer (NSCLC). However, data on this combination for elderly patients with NSCLC are insufficient., Methods: Eligibility criteria were no prior chemotherapy, Stage IIIB or IV NSCLC, performance status 0-1, age ≥ 75 years, and adequate hematological, hepatic, and renal functions. Carboplatin was administered on day 1 and S-1 was administered orally, twice a day, between days 1 and 14, repeated every 3 weeks. In phase I, the primary purpose was determination of the recommended dose. Starting doses of carboplatin and S-1 were area under the curve (AUC) of 4 and 80 mg/m 2 /day, respectively. In the extension study, the effects and tolerability of this combination therapy of recommended dose were confirmed., Results: A total of 10 patients were entered into phase I and 14 patients were entered into the extension study. The recommended doses for this drug combination are AUC 5 for carboplatin and 80 mg/m 2 /day every 3 weeks for S-1. With carboplatin and S-1 combination therapy at the recommended dose, the response rate was 30.0% [95% confidence interval (CI) 12-54%] and the disease control rate was 90.0% (95% CI 68-99%). Thrombocytopenia and neutropenia were major adverse events., Conclusions: The recommended doses for this combination therapy are carboplatin AUC 5 and S-1 80 mg/m 2 /day every 3 weeks, and this combination is effective with tolerable toxicities for advanced NSCLC patients ≥ 75 years old.

Purpose: Immune checkpoint inhibitors (ICIs) are an effective subsequent-line treatment for patients with advanced non-small cell lung cancer (NSCLC). However, it remains unclear whether the efficacy and safety of subsequent-line ICI monotherapy in elderly patients (aged ≥ 75 years) are similar to that in non-elderly patients. Therefore, we aimed to investigate the efficacy and safety of ICI monotherapy in pretreated elderly patients with NSCLC., Methods: Between January 2016 and February 2018, 131 elderly patients with advanced NSCLC who received subsequent-line ICI monotherapy at 13 Japanese institutions were enrolled in this study. Baseline characteristics, the efficacy of ICI treatment, and adverse events were evaluated., Results: Ninety-eight men and 33 women (median age 77 [range 75-87] years) were enrolled. Among those who received subsequent-line ICI monotherapy, the overall response, disease control rates, median progression-free survival (PFS), and overall survival (OS) were 27.4%, 61.8%, 4.5 months, and 16.0 months, respectively. Adverse events such as anorexia, fatigue, pneumonitis, and hypothyroidism were observed. There were two treatment-related deaths due to pneumonitis and thrombocytopenia. Subsequent-line ICI monotherapy in patients with good performance status (PS), receiving steroids for immune-related adverse events (irAEs), and exhibiting partial response (PR) was associated with improved PFS, as well as OS in patients with good PS and PR., Conclusions: Subsequent-line ICI monotherapy in elderly patients, with previously treated NSCLC, was effective, safe and showed outcomes equivalent to those in non-elderly patients. Immunotherapy provides a survival benefit for elderly patients, who exhibit its efficacy and a favorable general condition.

Background: Pseudomyxoma peritonei (PMP) is a rare malignancy, and there is insufficient evidence about systemic chemotherapy for this disease., Methods: We retrospectively evaluated the efficacy and safety of a chemotherapeutic regimen with 5-fluorouracil and oxaliplatin (modified FOLFOX6, mFOLFOX6) for patients with unresectable pseudomyxoma peritonei. Patients who received the therapy between April 2000 and February 2019 at the Department of Medical Oncology, Tohoku University Hospital, were enrolled in this study., Results: Eight patients were treated with mFOLFOX6. The sites of primary tumor were appendix in six patients, ovary in a patient, and urachus in a patient. Six patients received surgery. Seven patients had histologically high-grade PMP, and one patient had low-grade PMP. The median follow-up duration was 27.2 months. All the patients had non-measurable regions as the targets of tumor response. Non-complete response or non-progressive disease was observed in seven patients, with a disease control rate of 87.5%. The median progression-free survival and overall survival were 13.0 months and 27.9 months, respectively. An obvious reduction in the symptoms was observed in two patients. Five patients experienced decline in the serum tumor markers, CEA or CA19-9. The grade 3/4 toxicity that was observed was grade 4 neutropenia in one patient and grade 3 neutropenia in two patients., Conclusions: mFOLFOX6 might be an effective and tolerable treatment option for patients with unresectable PMP. To our knowledge, this is the first case series of mFOLFOX6 in patients with unresectable PMP and the first case series of systemic chemotherapy for Asian patients with unresectable PMP.

Irinotecan is effective for the treatment of metastatic colorectal cancer (mCRC) and advanced pancreatic cancer (aPC). However, these treatments are often limited due to the incidence of severe neutropenia. We identified risk factors for severe neutropenia in patients with mCRC or aPC, receiving irinotecan-based chemotherapy regimens. The study selected 104 patients (mCRC: 53 and aPC: 51) who received irinotecan-based chemotherapy between January 2014 and May 2018 and who were included in the present study. The initial dose of irinotecan was 150 mg/m 2 in all patients, and patients with a lower initial dose of irinotecan were excluded. Severe neutropenia (grade ≥ 3) occurred in 56 patients (53.8%). Multivariable Cox proportional hazards analysis indicated that modified FOLFIRINOX (mFOLFIRINOX) and serum total bilirubin (T-Bil) were significant risk factors for severe neutropenia. Moreover, with receiver-operating characteristic (ROC) curve analysis, the cutoff for T-Bil was found to be 0.7 mg/dL. Among patients treated with mFOLFIRINOX therapy, the incidence of severe neutropenia was significantly higher in patients with high level of T-Bil (> 0.7 mg/dL) than in those without it (93.8% vs 55.0%, P = 0.006). A chemotherapy regimen (modified FOLFIRINOX therapy) and T-Bil > 0.7 mg/dL were significant risk factors for severe neutropenia in patients receiving 150 mg/m 2 irinotecan.

Background/aim: It remains unclear which chemotherapeutic regimens are better for the addition of bevacizumab. We conducted an exploratory randomized phase II trial comparing first-line S-1 plus cisplatin with bevacizumab and pemetrexed plus cisplatin with bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC)., Patients and Methods: Chemotherapy-naïve patients received S-1 (80 mg/m 2 ) from day 1 to day 14 plus cisplatin (80 mg/m 2 ) on day 1 with bevacizumab (15 mg/kg) on day 1, followed by maintenance with bevacizumab plus S-1 (SCB) on day 1 every 3 weeks and pemetrexed (500 mg/m 2 ) on day 1 plus cisplatin (75 mg/m 2 ) on day 1 with bevacizumab (15 mg/kg) on day 1 followed by maintenance bevacizumab plus pemetrexed (PCB) on day 1 every 3 weeks. The expression of thymidylate synthase (TS) was analyzed using immunohistochemistry., Results: Forty-eight patients were enrolled in this study, and eligible patients were randomly assigned at 1:1 ratio to receive SCB (n=24) or PCB (n=24). The median number of chemotherapy and maintenance therapy for SCB and PCB was 4 (range, 1-6 cycles) and 4 (range, 2-6 cycles), and 5 (range, 0-39 cycles) and 5 (range, 0-28 cycles), respectively. The overall response rate (ORR) for PCB and SCB were 54.2% and 83.3%, respectively (p=0.06). The median progression-free survival (PFS) and overall survival (OS) for PCB and SCB were 406 and 351 days, (p=0.96), and 678 and 1190 days, respectively (p=0.23). The mild adverse events were observed in both regimens. TS expression was more predictive of the chemotherapeutic response in SCB compared to PCB, but not for PFS., Conclusion: The combination regimen of SCB was identified as having a similar activity and tolerability to that of PCB in patients with advanced non-squamous NSCLC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is effective as first-line chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive EGFR mutations. However, whether the efficacy of second-line cytotoxic drug chemotherapy after first-line EGFR-TKI treatment is similar to that of first-line cytotoxic drug chemotherapy in elderly patients aged ≥ 75 years harboring sensitive EGFR mutations is unclear. Therefore, we aimed to investigate the efficacy and safety of cytotoxic drug chemotherapy after first-line EGFR-TKI treatment in elderly patients with NSCLC harboring sensitive EGFR mutations., Methods: We retrospectively evaluated the clinical effects and safety profiles of second-line cytotoxic drug chemotherapy after first-line EGFR-TKI treatment in elderly patients with NSCLC harboring sensitive EGFR mutations (exon 19 deletion/exon 21 L858R mutation). Between April 2008 and December 2015, 78 elderly patients with advanced NSCLC harboring sensitive EGFR mutations received first-line EGFR-TKI at four Japanese institutions. Baseline characteristics, regimens, responses to first- and second-line treatments, whether or not patients received subsequent treatment, and if not, the reasons for non-administration were recorded., Results: Overall, 20 patients with a median age of 79.5 years (range 75-85 years) were included in our analysis. The overall response, disease control, median progression-free survival, and overall survival rates were 15.0, 60.0%, 2.4, and 13.2 months, respectively. Common adverse events included leukopenia, neutropenia, anemia, thrombocytopenia, malaise, and anorexia. Major grade 3 or 4 toxicities included leukopenia (25.0%) and neutropenia (45.0%). No treatment-related deaths were noted., Conclusion: Second-line cytotoxic drug chemotherapy after first-line EGFR-TKI treatment among elderly patients with NSCLC harboring sensitive EGFR mutations was effective and safe and showed equivalent outcomes to first-line cytotoxic drug chemotherapy.

The combinations of oral fluoropyrimidines and cisplatin such as capecitabine and cisplatin (XP) or S-1 and cisplatin (SP) are regarded as a standard therapy against unresectable, recurrent, or advanced gastric cancer (AGC). Especially, SP is the most common regimen against AGC in Japan. For patients with human epidermal growth factor receptor type 2 (HER2)-positive AGC, trastuzumab, a monoclonal antibody targeting HER2 antibody, is additionally used in combination. Although trastuzumab in combination with XP (trastuzumab-XP) have been widely accepted, the efficacy of trastuzumab in combination with SP (trastuzumab-SP) lacks sufficient verification. The aim of the present study is to validate the comparability of trastuzumab-SP to trastuzumab-XP. Patients with HER2-positive AGC were assigned to the trastuzumab-XP or trastuzumab-SP group. We then retrospectively compared the efficacy and safety between both groups. As a first-line chemotherapy, trastuzumab in combination with XP or SP was administered to 58 patients: 28 with trastuzumab-XP and 30 with trastuzumab-SP. In the trastuzumab-XP group, response rate (RR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) were 39.3%, 89.3%, 7.9 months, and 20.0 months, respectively. In the trastuzumab-SP group, RR, DCR, mPFS and mOS were 50.0%, 86.7%, 6.9 months, and 16.7 months, respectively. No significant difference in efficacy was observed between both groups. Severe hand-foot syndrome was observed more frequently in the trastuzumab-XP group than in the trastuzumab-SP group (14.3% vs. 0%, p = 0.05). Trastuzumab in combination with SP is a potential first-line therapeutic option for patients with HER2-positive AGC.

A woman in her 70s was confirmed as presenting with multiple liver and lung metastases from transverse colon cancer. After undergoing resection of the primary lesion, partial response(PR)was achieved after undergoing the first regimen (sLV5FU2 and bevacizumab[Bmab]); therefore, partial hepatectomy was performed. Adjuvant chemotherapy was administered for 7 months, but liver metastasis recurrence, multiple lung metastases, and brain metastasis were confirmed. As the brain metastasis was a single lesion and was accompanied by symptoms, resection of the lesion was performed. Treatment with regorafenib was initiated, but Grade 3 severe erythema multiforme was detected, and the treatment had to be discontinued. Therefore, combined TFTD and Bmab therapy was initiated as the third regimen. Liver and lung metastases were maintained as stable disease(SD), and the treatment was continued for approximately 1 year together with stereotaxic radiation therapy for the newbrain metastatic lesion. The utility of combined TFTD and Bmab therapy has been reported in a phase II trial, and it has also been indicated that Bmab is effective for reducing brain edema. As this treatment was effective in this case, we will report on it together with a discussion of the literature.

Purpose: Amrubicin is one of the most active chemotherapeutic drugs for small cell lung cancer (SCLC). Previous studies reported its effectiveness and severe hematological toxicity. However, the efficacy of amrubicin monotherapy in elderly patients with SCLC has not been described. The objective of this study was to investigate the feasibility of amrubicin monotherapy in elderly patients and its efficacy for relapsed SCLC., Methods: A retrospective cohort study design was used. We retrospectively evaluated the clinical effects and adverse events of amrubicin treatment in elderly (≥70 years) SCLC patients with relapsed SCLC., Results: Between November 2003 and September 2015, 86 patients (aged ≥70 years) received amrubicin monotherapy for relapsed SCLC at four institutions. There were 42 cases of sensitive relapse (S) and 44 of refractory relapse (R). S cases with median age of 75 years (range 70-85 years) and R cases with median age of 74 years (range 70-84 years) were included in our analysis. The median number of treatment cycles was three (range 1-9), and the response rate was 33.7% (40.5% in the S and 27.2% in the R cases). Median progression-free survival time was 4.0 months in the S and 2.7 months in the R patients (p = 0.013). Median survival time from the start of amrubicin therapy was 7.6 months in the S and 5.5 months in the R cases (p = 0.26). The frequencies of grade ≥3 hematological toxicities were as follows: leukopenia, 60.4%; neutropenia, 74.4%; anemia, 11.6%; thrombocytopenia, 16.2%; and febrile neutropenia, 17.4%. Treatment-related death was observed in one patient., Conclusion: Although hematological toxicities, particularly neutropenia, were severe, amrubicin showed favorable efficacy, not only in the S but also in the R cases, as shown in previous studies. Amrubicin could be a preferable standard treatment in elderly patients with relapsed SCLC. These results warrant further evaluation of amrubicin in elderly patients with relapsed SCLC by a prospective trial.

Background: The aim of our study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin in combination with thoracic radiotherapy for patients with locally advanced stage III non-small cell lung cancer (NSCLC)., Methods: Weekly nab-paclitaxel plus carboplatin was administered intravenously for 6 weeks. Doses of each drug were planned as follows: level 1, 40/2; level 2, 60/2; level 3, 80/2 (nab-paclitaxel [mg/m 2 ]/carboplatin [area under the plasma concentration time curve mg/ml/min]). Concurrent thoracic radiotherapy was administered in 2-Gy fractions 5 times weekly, to a total dose of 60 Gy., Results: Fourteen patients were enrolled in the present study. Eleven (78%) patients received full cycles (6 cycles) of chemotherapy, and 12 (86%) patients received 60 Gy of thoracic radiotherapy. At level 1, none of 3 patients experienced a dose-limiting toxicity (DLT). At level 2, 2 of 7 patients developed grade 3 diarrhea, grade 3 hyponatremia, grade 3 fatigue, and grade 3 esophagitis. Therefore, 4 patients were started at dose level 3 and none developed a DLT. No pulmonary toxicities, such as interstitial pneumonitis and treatment-related deaths, were observed at either level. Therefore, level 3 was considered the MTD and level 3 was defined as the RD. An objective response was observed in 71.4% of all patients., Conclusions: This regimen is feasible and well tolerated for the treatment of patients with unresectable locally advanced NSCLC.

Although prognosis in patients with localized osteosarcoma has been dramatically improved by the introduction of multiple chemotherapy agents known as combination chemotherapy, there is growing concern about the development of secondary malignant neoplasms. We report the case of a 13-year-old girl in whom the diagnosis of Ewing sarcoma of bone localized on the shaft of left femur was made 2 years after successful treatment without radiotherapy for osteosarcoma of right proximal femur. EWS-FLI1 fusion gene was detected by reverse transcriptase-polymerase chain reaction. To our knowledge, this is the first case with Ewing sarcoma of the bone as a secondary malignant neoplasm developed in osteosarcoma survivor. We collected 15 cases, included this case, with secondary Ewing sarcoma family of tumor by utilizing the PubMed search and might consider the causes of this secondary cancer.

Background: The effects of first-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies in patients with small-cell lung cancer (SCLC). Therefore, the objective of our study was to determine the relationships between progression-free survival (PFS) or post-progression survival (PPS) and OS after first-line chemotherapy in elderly patients with extensive disease-SCLC (ED-SCLC), using individual level data., Methods: Between July 1998 and December 2014, we analyzed 57 cases of elderly patients with ED-SCLC who were treated with carboplatin and etoposide as first-line chemotherapy. The relationships between PFS and PPS with OS were analyzed at an individual level., Results: Spearman rank correlation and linear regression analyses showed that PPS was strongly correlated with OS (r = 0.92, P < 0.05, R 2  = 0.83) and PFS was moderately correlated with OS (r = 0.76, P < 0.05, R 2  = 0.25). The best response at second-line treatment and the number of regimens after progression beyond first-line chemotherapy were both significantly associated with PPS (P < 0.05)., Conclusions: PPS has a stronger impact on OS than PFS in elderly ED-SCLC patients after first-line chemotherapy. In addition, the response at second-line treatment and the number of additional regimens after first-line treatment are significant independent prognostic factors for PPS. These results suggest that OS in elderly ED-SCLC patients may be influenced by treatments subsequent to first-line chemotherapy; however, this remains to be verified with prospective studies., (© 2016 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: We conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD), the recommended dose (RD) and the safety profile of amrubicin (AMR) plus paclitaxel (PTX) combination regimen for patients with previously treated non-small cell lung cancer (NSCLC)., Patients and Methods: PTX was administered at a fixed dose of 150 mg/m(2)/day on day 1 and AMR was intravenously administered at a starting dose of 25 mg/m(2)/day on days 1-3, and this was repeated every 4 weeks. Doses of each drug were planned as follows-level 0, 20/150; level 1, 25/150; level 2, 30/150; level 3, 30/180 AMR mg/m(2) per day/PTX mg/m(2) per day., Results: Twelve patients were enrolled in this study. The dose-limiting toxicity (DLT) of the regimen was assessed during the first cycle. At level 1, all three patients developed a DLT due to grade 4 neutropenia lasting >4 days, grade 4 thrombocytopenia and grade 3 febrile neutropenia. Therefore, level 1 was considered the MTD and level 0 was selected as the RD. Objective responses were seen in two patients (response rate 16.7 %). Overall disease control rate was 91.7 %., Conclusions: The combination of AMR and PTX is a feasible and well-tolerated regimen for the treatment of patients with previously treated advanced NSCLC. Although our study included a small number of patients, encouraging disease control and progression-free survival were achieved at the recommended doses. Further clinical trials are warranted.

Background: Neuroendocrine carcinoma (NEC) is a rare tumor type, and a standard therapy for NEC has not yet been established. From 2008 to 2013, carboplatin-etoposide combination therapy has been used to treat almost all NEC patients in our department, and the objective of the present study was to investigate the therapeutic effects of carboplatin-etoposide combination therapy in NEC., Methods: This retrospective study was conducted based on medical records from 2008 to 2013. Eligible patients had been pathologically diagnosed with NEC and had received a carboplatin-etoposide combination as first-line chemotherapy., Results: Nineteen patients were included in the study, and the overall response rate was 47.4%. The median overall survival was 12.7 months, and the median progression-free survival was 7.0 months. The median survival times were 10.8 and 8.9 months in NEC patients with primary sites in the gastrointestinal tract and hepatobiliary-pancreatic system, respectively. Median progression-free survival times were 5.0 and 3.1 months, respectively. The major toxicities were grade 3 and 4 leukopenia (73.7%), neutropenia (78.9%), anemia (31.6%), and thrombocytopenia (26.3%)., Conclusions: Carboplatin-etoposide combination therapy for NEC may have comparable effectiveness and milder adverse events than cisplatin-etoposide combination therapy., (© 2015 S. Karger AG, Basel.)

Aim: The benefit of preoperative chemotherapy is evaluated in order to clarify the relationship of tumor site with hepatic vessels for hepatectomy. Tumor location in relation to intrahepatic vessels is critical in the decision to operate, but the argument for this concept remains insufficient. Currently, the response rate is evaluated by the decrease in size or number of tumors but not by hepatic resection range., Patients and Methods: We evaluated 32 patients who underwent hepatectomy after chemotherapy for liver metastases from colorectal cancer (CLM). Tumor diameter was defined by contrast computed tomographic imaging before both chemotherapy and surgery. The targeted vessels were those in the main Glisson capsule and hepatic vein and were indicated to change in the resected area by their treatment., Results: Tumor size decreased, increased or remained unchanged in 62 (68.9%), 27 (30.0%) and one (1.1%) tumor, respectively. Out of the 29 tumors, reduced resection volume was achieved in 12 (37.9%), and the difference in volume was 17.4±4.15 ml. A significant positive correlation was found between tumor shrinkage rate and final distance from the attached vessels (p=0.017), and a shrinkage rate of 63.6±12.4% was necessary for a tumor to be separated from an attached vessel. The final distance was significantly positively correlated with tumor shrinkage speed (p=0.0027), and a shrinkage speed of 0.64±0.12%/day was expected to enable a a tumor to be separated from its attached vessel., Conclusion: Chemotherapy, especially by favorable combination with molecular targeting agents, even for resectable CLM appears to be acceptable and may lead to increased performance of radical surgical resection., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Purpose: Gefitinib is an effective first-line chemotherapy for advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, whether second-line platinum combination chemotherapy after first-line gefitinib treatment shows similar effects to first-line platinum combination chemotherapy in these patients remains unclear. Therefore, we here aimed to investigate the efficacy of platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations., Methods/patients: We retrospectively evaluated the clinical effects of second-line platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations (exon 19 deletion or exon 21 L858R mutation) at five institutions. All patients were initially treated with gefitinib (250 mg/day) followed by platinum combination chemotherapy as second-line chemotherapy., Results: Between January 2006 and December 2012, 42 patients [8 men, 34 women; median age, 63 years (range 39-75 years)] were enrolled. The overall response rate, disease control rate, and median progression-free survival (PFS) were 26.2, 61.9%, and 5.1 months, respectively, after the second-line treatment. The corresponding values for first-line gefitinib treatment were 69.0, 95.2%, and 11.1 months, respectively. Moreover, second-line platinum combination chemotherapy with pemetrexed or bevacizumab-containing regimens was independently associated with improved PFS., Conclusions: Second-line platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations was effective and showed equivalent outcomes to first-line platinum combination chemotherapy. After failure of first-line gefitinib therapy, second-line platinum combination chemotherapy with pemetrexed or bevacizumab might result in improved PFS.

Purpose: The prognosis of non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) is unclear. To assess the prognosis of NSCLC patients with ILD treated with platinum-based chemotherapy, we retrospectively analyzed the clinical course of those with ILD., Methods: One hundred and four NSCLC patients with ILD treated with platinum-based chemotherapy at Shizuoka Cancer Center between August 2002 and June 2013 were retrospectively reviewed., Results: The combination of carboplatin with paclitaxel was most frequently used as the first-line treatment for NSCLC patients with ILD (61 %). The overall response rate was 38 % in 104 NSCLC patients with ILD treated with platinum-based chemotherapy. In all patients, median progression-free survival and overall survival were 4.8 and 9.9 months, respectively. During first-line platinum-based chemotherapy, 9 % of the 104 patients with ILD developed chemotherapy-related exacerbation of ILD. Multivariate analysis demonstrated that clinical stage was a significantly independent prognostic factor (hazard ratio 0.517; 95 % confidence interval 0.314-0.842, p = 0.0079). Patients with clinical stage IV or recurrence after surgical resection showed poor prognosis (median survival time 8.5 months)., Conclusions: Our study suggests that the prognosis of NSCLC patients with ILD is poor. The risk of exacerbation of ILD in patients treated with platinum-based chemotherapy as the first-line treatment was slightly lower than in previous reports.

We describe a case of liver metastasis of colorectal cancer that became resectable after bevacizumab (Bmab), CPT-11, and S-1 ie Bmab+IRIS combination chemotherapy. A 65-year-old man experienced repeated constipation and diarrhea in August of 2013. Colonoscopy was conducted by a local doctor, and a tumor(diagnosed as adenocarcinoma tub1 by biopsy)was found in the upper rectum. Computed tomography performed at our institution detected synchronous liver metastasis. On September 9, laparoscopic rectal anterior resection was performed to prevent metastasis to the ileus, and on October 9, the patient began receiving Bmab+IRIS combination chemotherapy. Before chemotherapy, 3 metastases with a maximum diameter of 7 cm diameter)were observed in the right lobe of the liver. After 4 courses of chemotherapy, their maximum diameter was 3 cm, which allowed resection. Ultimately, the metastases were completely resected. Conversion of non optimal resection cases of liver metastases to optimal cases by using Bmab+IRIS chemotherapy is extremely rare. We suggest that Bmab+IRIS chemotherapy could be an option for conversion of non optimal liver resection cases to optimal cases. We report this rare case and discuss the implications of adjuvant chemotherapy for this patient.

A 46-year-old man developed a fever and cough, and computed tomography showed multiple, nodular infiltrative shadows in lungs. He was diagnosed as having intravascular large B-cell lymphoma (IVLBCL). Brain magnetic resonance imaging (MRI, T2W1) showed an abnormal signal area in the pons, which was IVLBCL involvement. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy and intrathecal (I.T.) injection of methotrexate, cytarabine and prednisolone were selected. Complete remission (CR) was achieved and pontine involvement disappeared. A total of 8 courses of R-CHOP therapy and 4 courses of I.T. were performed. CR has been maintained for 1 year and 2 months.

Background: Cisplatin plus pemetrexed is a standard front-line chemotherapeutic regimen for inoperable malignant pleural mesothelioma (MPM). However, no clinical trials have compared the efficacy of cisplatin plus pemetrexed and cisplatin plus gemcitabine, which may be comparable based on previous phase II study results. This study aimed at evaluating the efficacy of cisplatin plus pemetrexed and comparing it with that of cisplatin plus gemcitabine in Japanese MPM patients., Methods: From July 2002 to December 2011, 13 and 17 consecutive patients with inoperable MPM were treated with cisplatin plus gemcitabine and cisplatin plus pemetrexed, respectively, at the Shizuoka Cancer Center. We reviewed the medical charts of these patients and evaluated their characteristics as well as data regarding drug toxicity and antitumor efficacy., Results: The response rates were 15% and 35% in the cisplatin plus gemcitabine and cisplatin plus pemetrexed groups, respectively (P=0.4069), while disease control rates were 77%, and 82%, respectively (P=0.9999). Progression-free survival was significantly higher with cisplatin plus pemetrexed (median, 215.5 days) than with cisplatin plus gemcitabine (median, 142.5 days) (P=0.0146; hazard ratio [HR], 0.3552). Overall survival showed a tendency towards being superior with cisplatin plus pemetrexed (median, 597.5 days) compared with cisplatin plus gemcitabine (median, 306.5 days) (P=0.1725, HR, 0.5516). Hematological toxicities, especially thrombocytopenia and neutropenia, tended to be more frequent and severe in the cisplatin plus gemcitabine group., Conclusions: Cisplatin plus pemetrexed may be superior and should continue to be the standard front-line chemotherapeutic regimen for inoperable MPM., (© 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

The effects of first-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies in patients with non-small cell lung cancer (NSCLC). We examined whether progression-free survival (PFS), post-progression survival (PPS), or tumor response could be valid surrogate endpoints for OS after first-line chemotherapies in advanced NSCLC by using individual-level data, given the lack of research in this area. Between April 2009 and June 2011, 50 patients with advanced non-squamous NSCLC treated with cisplatin and pemetrexed as first-line chemotherapy were analyzed. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.89, P < 0.05, R2 = 0.79), PFS was moderately correlated with OS (r = 0.67, P < 0.05, R2 = 0.39), and tumor shrinkage was weakly correlated with OS (r = 0.36, P < 0.05, R2 = 0.14). Performance status at the beginning of second-line treatment, the best response to second-line treatment, and number of regimens used after progression following first-line chemotherapy were significantly associated with PPS (P < 0.05). Analysis of individual-level data suggested that PPS could be used as a surrogate for OS in patients with advanced non-squamous NSCLC with unknown oncogenic driver mutations and therefore limited options for subsequent chemotherapy. Our findings also suggest that subsequent treatment after disease progression following first-line chemotherapy may greatly influence OS. These results should be validated in other larger populations.

The patient was a 74-year-old man who was found to have a cutaneous mass on his left shoulder in February 2012. Because the mass bled easily and was tending to grow, total resection of the cutaneous tumor, which measured approximately 5 cm x 3 cm, was performed in July. Histopathological examination revealed a tumor that extended from the dermis to the cutaneous adipose tissue, but no invasion of the epidermis was seen. The tumor cells were plasmacytoid cells ranging in size from small to intermediate, and there was no nuclear irregularity. They had a high nuclear-cytoplasmic ratio, and nucleoli were observed. The tumor cells were CD4-positive, CD56-positive, and CD123-positive, and they were AE1/AE3-negative, CD3-negative, CD20-negative, and myeloperoxidase-negative. (18)F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT), a bone marrow examination, etc., were performed, but no lesions were detected at other sites. Based on the above findings a diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN), Stage IEA, was made. Because the patient had limited-stage BPDCN and was elderly, we treated him with a simultaneous combination of low-dose DeVIC (dexamethasone, VP16, ifosfamide, and carboplatin) therapy and local radiation therapy (LRT) and sustained a complete remission for approximately 1 year. Simultaneous combination of non-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy and LRT appeared to be useful in the treatment of limited-stage BPDCN even in the elderly.

A 65-year-old man was diagnosed with angioimmunoblastic T-cell lymphoma (AITL) with bone marrow (BM) infiltration and myelofibrosis (MF). The BM infiltration and the condition of the MF improved following CHOP therapy (cyclophosphamide hydrate, doxorubicin hydrochloride, vincristine sulfate, and prednisolone). After complete remission was achieved, early central nervous system recurrence was noted, with no evidence of BM infiltration or MF. The lymph nodes and BM were examined for cytokines by immunohistochemical staining with monoclonal murine antibodies. The lymphoma cells were positive only for platelet-derived growth factor (PDGF) and negative for basic fibroblast growth factor, fibronectin, vascular endothelial growth factor, transforming growth factor-β (TGF-β), tumor necrosis factor α, interleukin-1β, and interleukin-6. It was thus inferred that the lymphoma cells producing PDGF caused the MF, and that the absence of MF at relapse may have been attributable to the absence of BM infiltration. There have been seven reported cases of AITL with intercurrent MF, although cytokine data (elevations of blood PDGF and TGFβ levels) are available for only one case. The present report is to our knowledge the only report of a case of AITL complicated by MF for which the results of immunohistostaining with anticytokine antibodies are available.

A 56-year-old man developed epistaxis, hoarseness, and swelling of a finger in March 2010. On the basis of biopsies of the masses in the pharynx and finger, he was diagnosed with extramedullary plasmablastic plasmacytoma, with somewhat immature CD45(+), MPC-1(-), and CD49e(-). CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and VCAP (vincristine, cyclophosphamide, doxorubicin, and prednisolone) therapy was ineffective, but combination therapy with thalidomide and dexamethasone was highly effective. Thalidomide monotherapy successfully maintained partial remission for approximately 7 months. A mass appeared in the right neck in February 2011, and a biopsy confirmed recurrence. Changes to CD45 negativity and MPC-1 partial positivity were seen, while CD49e negativity persisted, suggesting that the plasmablastic plasmacytoma had reverted to a more immature state. Bortezomib therapy was started in March 2011 and was effective. However, during the second round of treatment, the patient developed acute lung injury, which was improved by steroid pulse therapy. After the discontinuation of bortezomib, the extramedullary mass increased rapidly, and the patient died of multiple organ failure. An autopsy showed that plasmablastic plasmacytomas had infiltrated into multiple organs. Extramedullary plasmacytomas and those that revert to an immature state are associated with a poor prognosis, so further treatment improvements are needed in the future.

Background: Based on the results of phase I/II studies, S-1 plus cisplatin (CDDP) and vinorelbine (VNR) plus CDDP are commonly used chemoradiotherapeutic regimens for the treatment of non-small cell lung cancer(NSCCLC) in Japan. However, there have been no studies that have compared S-1 and CDDP combined with thoracic radiotherapy (TRT) with VNR and CDDP combined with TRT., Patients and Methods: A total of 39 and 50 patients with stage III non-small cell lung cancer (NSCLC) were treated with S-1 and CDDP plus concurrent TRT, or with VNR and CDDP plus concurrent TRT, respectively, between 2002 and 2010., Results: In the S-1 plus CDDP plus TRT group, the median progression-free survival (PFS) and the median overall survival (OS) were 327 days and 1012 days, respectively. In the VNR plus CDDP plus TRT group, the median PFS and the median OS were 328 days and 905 days, respectively. The differences in the PFS and OS were not statistically significant. Grade 3 or more leukopenia and neutropenia were significantly more common in the VNR plus CDDP plus TRT group. Grade 3 or more thrombocytopenia, esophagitis and eruption tended to be more common in the S-1 plus CDDP plus TRT group., Conclusion: Due to the difference in the toxicity profiles of the two combinations, S-1 plus CDDP plus TRT or VNR plus CDDP plus TRT should be selected depending on each patient's baseline characteristics.

Reversible posterior leukoencephalopathy syndrome (RPLS) is uncommon neurological syndrome that is characterized by specific clinical and radiologic findings. Previous reported associations of RPLS include hypertension, eclampsia, renal impairment and drugs. Prompt diagnosis and therapy is critical to ensure resolution of the neurological disability. Some cases have been reported in association with the increased use of antineoplastic agents in cancer patients. We report the case of a 62-year-old man who was diagnosed with RPLS after receiving carboplatin and paclitaxel chemotherapy for lung cancer. This case appears to be the first recognized association of RPLS with this regimen.

Background/aims: Surgical indications for resection of synchronous metastasis from colorectal cancer (CRC) and the optimal timing of hepatectomy are still controversial and widely debated., Methodology: Synchronous and multiple metastatic liver tumors were detected in 57 patients since May 2005. Our treatment policy was to perform hepatectomy if the resection could be done with no limit on size and number of tumors. However, if curative resection could not be done, chemotherapy was begun and timing for the possibility of a radical operation was planned immediately., Results: In 37 patients whose tumors were located only in the liver, primary tumor resection was performed in 16 patients and after tumor-decreasing by chemotherapy, in 7 patients. In 20 patients in whom chemotherapy was performed first, after controlling the distant metastasis, hepatectomy was performed in 3 patients and staged hepatectomy was performed in 10. Recurrence was detected after hepatectomy in 75.0% of simultaneous resection cases and in 70.0% of staged cases. In the recurrence cases, early detection after tumor resection occurred in 58.3% of the simultaneous and 14.2% of the staged., Conclusions: The present data show that neoadjuvant chemotherapy does not increase the risk of postoperative complications or the surgical difficulties of hepatectomy for colorectal metastases.

A 69-year-old woman, who had been diagnosed as having Sjögren's syndrome at 37 years old and mixed connective tissue disease at 42 years old, was under treatment with oral prednisolone. In 2009, she was diagnosed as having active systemic lupus erythematosus, and started on treatment with tacrolimus at 3 mg/day. In 2010, para-aortic lymphadenopathy and superficial multiple lymphadenopathy were detected. Tacrolimus was discontinued. Axillary lymph node biopsy revealed Epstein-Barr (EB) virus-negative CD5-positive diffuse large B-cell lymphoma (DLBCL). The patient was classified into clinical stage IIIA and as being at high risk according to the international prognostic index. After the discontinuation of tacrolimus, the lymph nodes reduced temporarily in size. In January 2011, the lymphadenopathy increased again, and the patient received a total of 8 courses of therapy with rituximab, pirarubicin, vincristine, cyclophosphamide and prednisolone, followed by intrathecal injection to prevent central nervous system infiltration, which was followed by complete remission. In February 2012, fluorodeoxyglucose positron emission tomography showed relapse in multiple lymph nodes and central nervous system infiltration. The patient was considered to have iatrogenic lymphoproliferative disorder classified as "other iatrogenic immunodeficiency-associated lymphoproliferative disorders" by the WHO, and this is the first reported case of CD5-positive DLBCL and central nervous system infiltration following administration of the drug. The patient was considered to have a poor prognosis as EB virus was negative, discontinuation of tacrolimus was ineffective and there was evidence of central nervous system infiltration.

We conducted a phase II study of S-1 and carboplatin combination regimen in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Chemotherapy-naïve patients with advanced NSCLC were treated with S-1 and carboplatin. S-1 was administered orally twice daily for 14 days and carboplatin AUC 5 on day 1 of each cycle, and this was repeated every 4 weeks. Twenty-nine patients were enrolled in this study. The main grade 3 or 4 toxicities observed during the first cycle were neutropenia (10.3%), thrombocytopenia (41%), and transaminase elevation. Objective responses were seen in 9 patients (response rate 31.0%). The median survival time and median progression-free survival were 16.0 months (95% CI, 12.1-19.0 months) and 4.5 months (95% CI, 3.2-6.1 months), respectively. Hematological adverse events reaching grade 3 or 4 were neutropenia (10.3%), anemia (3.4%), and thrombocytopenia (3.4%). No febrile neutropenia was detected. Nonhematological toxicities were also mild. Although grade 3 infection was observed in 1 patient, the patient improved without intervention. The combination of S-1 plus carboplatin is an active and well-tolerated regimen for the treatment of patients with advanced NSCLC. Further investigations are required to confirm our results in randomized trials., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

An 81-year-old man presented with right shoulder pain 10 months after surgery for non-small cell lung cancer (p- T3N0M0, Stage II b). FDG-PET revealed an increased uptake in the multiple bone and mediastinal lymph nodes, suggestive of recurrence of lung cancer. He was given combined chemotherapy of gemcitabine plus S-1 as first-line treatment. This regimen was performed as a phase I trial for an elderly patient with advanced non-small cell lung cancer, and the treatment proved effective. No toxic events were observed due to this therapy, so he was treated as an outpatient for one year. He was considered to have good quality of life.

The patient was an 86-year-old female who suffered from advanced non-small cell-lung cancer (cT4N3M1, Stage IV). She was treated with combined chemotherapy of gemcitabine and S-1 as first-line therapy. This regimen was performed as a phase I trial for elderly patients with advanced non-small cell lung cancer. The treatment assessment was evaluated as partial response. No toxic events were observed due to this therapy, so she was treated as an outpatient. She was considered to have good quality of life.

Here we report a rare case with perforation of gastric cancer responding to chemotherapy. The patient was a 74- year-old male who underwent abdominal ultrasonography and contrast CT because of body-weight lost and poor appetite in June, 2004 and whose lymph node(LN)swelling was seen in the level from the hepatic to the renal hilum. A gastric wall irregularity was also seen. We suspected gastric cancer with LN metastasis and carried out upper gastrointestinal endoscopy. Then it demonstrated type 2 advanced gastric cancer from the upper to the middle body. The pathological diagnosis of gastric tumor was poorly-differentiated adenocarcinoma containing por 2, tub 1, and pap. The patient was treated with S-1, CDDP and CPT-11 and remained ambulant. After completion of 1 course of chemotherapy, he complained of intense abdominal pain, so we carried out upper gastrointestinal endoscopy and found perforation in the stomach at the same location as the gastric cancer. Emergency total gastrectomy was performed at once. The histopathological finding showed disappearance of the cancer cell not only in the stomach but also accessory LN. Because the remnant LN metastasis was seen in the hepatic hilum at abdominal contrast CT after operation, S-1 was administered to the patient as 60 mg/m2/day in ambulant. Now, over 40 months after the operation, the patient has been alive with good performance status and disappearance of LN metastasis.

Objective: We conducted a phase I dose escalation study to determine the maximum tolerated dose, recommended dose, and safety profile of a biweekly gemcitabine and carboplatin combination regimen in the treatment of patients with completely resected nonsmall cell lung cancer (NSCLC)., Patients and Methods: Patients with completely resected pathologically documented stage IB, II, or IIIA NSCLC, performance status (ECOG) 0-1, with adequate bone marrow, renal, liver, and cardiac functions, were treated with gemcitabine and carboplatin. The starting dose was gemcitabine 800 mg/m2 on days 1 and 15 and carboplatin area under the time-concentration curve (AUC) 4 mg/mL/min on day 1. Gemcitabine was increased to 1000 mg/m2 (level 3). Carboplatin was increased to AUC 5 (level 2, 3). The regimen was performed every 4 weeks. The dose-limiting toxicity of the regimen was assessed during the first chemotherapy cycle., Results: Nine patients were enrolled in this study. All patients were assessed for safety. Grade 3 leukopenia occurred in 1 patient (11%) and grade 3/4 neutropenia occurred in 3 patients (33%). No other grade 3/4 toxicity was observed. No dose-limiting toxicity was experienced at dose levels 1, 2, and 3 of this schedule., Conclusion: Maximum tolerated dose was not reached in this study. Considering treatment continuation, the recommended dose for a phase II study is gemcitabine 1000 mg/m2 on days 1 and 15 and carboplatin AUC 5 on day 1, every 4 weeks. Biweekly administration of gemcitabine and carboplatin is a feasible and well-tolerated regimen for the treatment of patients with completely resected NSCLC as adjuvant chemotherapy.

We conducted a phase I study to determine the maximum tolerated dose, the recommended dose and the safety profile of S-1 and carboplatin combination regimen in the treatment of patients with advanced non-small-cell lung cancer. Chemotherapy-naive patients with advanced non-small-cell lung cancer were treated with S-1 and carboplatin. S-1 was administered orally twice daily for 14 days and carboplatin on day 1 of each cycle, and this was repeated every 4 weeks. Doses of each drug were planned as follows: level 1, 5/65; level 2, 5/80; level 3, 6/80 [carboplatin (area under the curve, mg/ml/min)/S-1 (mg/m/day)]. The dose-limiting toxicity of the regimen was assessed during the first chemotherapy cycle. Twelve patients were enrolled in this study. The main grade 3 or grade 4 toxicities observed during the first cycle were neutropenia (41%), thrombocytopenia (41%) and transaminase elevation. Two of three patients in level 2 had dose-limiting toxicity and this level was considered the maximum tolerated dose. Level 1 was selected as the recommended dose. Objective responses were seen in four patients (response rate 33%). The combination of S-1 plus carboplatin is a feasible and well-tolerated regimen for the treatment of patients with advanced non-small-cell lung cancer.

Objective: We conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD), the recommended dose (RD), and the safety profile of a weekly docetaxel and carboplatin combination regimen in the treatment of elderly patients with advanced nonsmall cell lung cancer (NSCLC)., Patients and Methods: Chemotherapy-naive patients with stage IIIB and IV NSCLC, >70 years of age, performance status (ECOG) 0-2, with adequate bone marrow, renal, liver and cardiac function, were treated with docetaxel and carboplatin. Docetaxel was given at escalated doses starting from 20 mg/m2/wk on days 1, 8, and 15, with an increment of 5 mg/m2 followed by carboplatin also administered at escalated doses starting from AUC 4 to 6 (mg/ml/min); the regimen was administered every 4 weeks. The dose limiting toxicity (DLT) of the regimen was assessed during the first chemotherapy cycle., Results: There were 25 patients enrolled in this study and assessed for safety. Neutropenia was the main DLT of the regimen; grade 3/4 neutropenia occurred in 5 patients (20%). Hematologic toxicities were mild, and included grade 3 thrombocytopenia in 1 patient (4%) and grade 3 anemia in 1 patient (4%). Nonhematologic toxicities were generally mild, and included grade 3 constipation in 1 patient (4%) and grade 3 renal disorder in 1 patient (4%). Objective responses were seen in 9 patients (response rate 36%)., Conclusions: The MTD was carboplatin AUC 5 on day 1 and docetaxel 30 mg/m2 on days 1, 8, and 15; therefore, the RD for the phase II study is carboplatin AUC 5 and docetaxel 30 mg/m2. The combination of docetaxel and carboplatin is a feasible and well-tolerated regimen for the treatment of elderly patients with advanced NSCLC. This regimen merits further investigation in phase II trials.

A 64-year-old man developed multiple myeloma (kappa light chain type), nephrotic syndrome, and renal insufficiency in 1993. A renal biopsy showed typical histological findings of light chain nephropathy: nodular glomerulosclerosis with deposition of kappa light chains in the mesangial area and subendothelial space of the glomerular capillary walls. Long-term intermittent MEVP chemotherapy (melphalan, 4 mg/d for 4 days; cyclophosphamide, 100 mg/d for 4 days; vincristine, 1 mg/d; prednisolone, 40 mg/d for 4 days) diminished proteinuria and improved renal function. In April 1999, a follow-up biopsy showed remarkable diminution of nodular lesions and disappearance of kappa light chain deposits. Although the prognosis of light chain nephropathy has been considered poor, long-term successful chemotherapy can clear light chain deposits and restore renal function.

A 54-year-old male was admitted to receive treatment by anticancer drug for advanced gastric cancer with liver metastases and carcinomatous peritonitis. Upper gastrointestinal series showed a Borrmann type 4 gastric cancer occupying the body and antrum, and a pathological diagnosis of papillary adenocarcinoma was made by endoscopic biopsy. Two cycles of neoadjuvant chemotherapy consisting of 5-FU and low-dose CDDP (FP therapy) were given. No effect was observed, so that the next chemotherapy schedule of sequential MTX/5-FU therapy was performed. We adopted the intermediate (MTX: 100 mg/m2 and 5-FU 600 mg/m2 weekly) dose regimen. When six courses of this regimen were completed, the primary lesion of the stomach was decreased to 60% and the metastatic liver tumor to 72%, basel on criteria for the evaluation of clinical effects of solid cancer chemotherapy. However, pylorous stenosis remained, and we performed gastrojejunostomy and biopsy of the regional lymph node to determine the response to the chemotherapy. A pathological examination of lymph node revealed metastatic papillary adenocarcinoma with xanthogranulomatous change, and was judged as an effect showing grade 2. He was discharged and had the outpatient hospital treatment. He died of exacerbation of carcinomatous peritonitis 10 months after his initial admission. The response duration for sequential MTX/5-FU therapy was 4 months. This therapy was usually effective in patients with poorly differentiated adenocarcinoma of the stomach. Our result indicates that this therapy can be effective for not only poorly differentiated adenocarcinoma but also papillary adenocarcinoma of the stomach in an advanced stage.

We describe a 45-year-old female who developed acute myelogenous leukemia (AML) associated with a mediastinal mass. The patient achieved a complete remission accompanied by resolution of the mediastinal mass following intensive chemotherapy alone. A review of the literature disclosed ten AML patients with a mediastinal tumor; all five patients who had mediastinal granulocytic sarcoma treated by local irradiation prior to developing AML, eventually relapsed as frank leukemia and died soon afterwards. On the other hand, three of the other five patients who simultaneously developed both a mediastinal tumor and overt AML achieved complete remission with combination chemotherapy. In conclusion, intensive chemotherapy should be considered for a patient with granulocytic sarcoma of the mediastinum, irrespective of the concomitant leukemia.