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Background: The Kidney Disease: Improving Global Outcomes group (KDIGO) defined acute kidney injury (AKI) as an elevation of serum creatinine (sCR) exceeding 0.3 mg/dl within 48 h. The widely used adverse events criteria for chemotherapy, Common Toxicity Criteria for Adverse Events Version 4.0 (CTCAE v4.0), also defined AKI as sCR exceeding 0.3 mg/dl, but with no provision of a time course. Here, we attempted to clarify the impact of AKI (CTCAE v4.0) during cisplatin-based chemotherapy on clinical outcome of patients with advanced urothelial cancer (UC)., Methods: This multicenter retrospective study included 230 UC patients who received cisplatin-based chemotherapy., Results: During the first chemotherapy course, AKI (CTCAE v4.0) episodes were observed in 61 patients (26.5 %), whereas only four patients (1.5 %) experienced AKI (KDIGO) episodes. Both the pretreatment estimated glomerular filtration rate (eGFR) and creatinine clearance by Cockcroft-Gault formula were not efficient predictors for the development of AKI (CTCAE v4.0). AKI (CTCAE v4.0) impacted renal function: at the start of second-course chemotherapy, the average eGFR of the patients with AKI (CTCAE v4.0) was 54.1 ml/min/1.73 m 2 , significantly lower than that of patients without AKI (CTCAE v4.0) (63.4 ml/min/1.73 m 2 ). As a result, only 57.4 % of patients with AKI (CTCAE v4.0) received the planned treatment at the second course. The survival of the patients who developed AKI (CTCAE v4.0) was significantly worse than that of the patients who did not. The 3-year OSs were 10.3 and 21.4 %, respectively (P = 0.02)., Conclusion: The present study demonstrated that AKI (CTCAE v4.0) during chemotherapy had a negative impact on both the intensity of subsequent chemotherapy and oncological outcomes.

Background: The standard regimen of systemic chemotherapy for patients with advanced urothelial cancer (UC) changed from methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) to gemcitabine and cisplatin (GC) in 2008 when the use of gemcitabine for UC began to be reimbursed by public health insurance in Japan. We examined its influence on the chemotherapy trend in elderly patients aged ≥80 years., Methods: Among 345 patients included in our previous multicenter retrospective cohort study (chemotherapy for urothelial carcinoma: renal function and efficacy study; CURE study), the outcome of 30 patients aged ≥80 years was reviewed before and after 2008 and compared with 315 young patients., Results: There were only 7 (4.6 %) elderly individuals among all registered patients before 2008, whereas the number increased to 23 (12 %) after 2008. Before 2008, only one elderly patient received MVAC, while GC (whose rate was similar to the rate in young patients) was administered to 13 patients (56.5 %) after 2008. The chemotherapeutic effect and overall survival (OS) rate was not significantly different between young and elderly patients. In the elderly treated with the GC regimen, the renal impairment rate after the first cycle was significantly higher, and the presence of distant metastases and renal impairment were independent prognostic factors in a multivariate analysis., Conclusion: Since GC was approved as the standard regimen for first-line chemotherapy in UC, selected elderly patients have been able to safely receive systemic chemotherapy like young patients. The clinical response rate and OS rate were similar to the young, but we need to monitor changes in renal function more closely in the elderly treated with GC.

Objective: The aim of the study is to clarify the clinical effects of first-line chemotherapy regimens for advanced urothelial cancer on clinical responses and survival of patients grouped by renal function., Methods: In this multicenter retrospective cohort study, 345 urothelial cancer patients received systemic chemotherapy for metastatic or unresectable disease in 17 centers (2004-10)., Results: Two hundred and forty-one patients were treated with methotrexate, vinblastine, doxorubicin and cisplatin/methotrexate, epirubicin and cisplatin (n = 136) or gemcitabine and cisplatin (n = 105) followed by carboplatin-based treatments, non-platinum treatments or other regimens. After 2008, gemcitabine and cisplatin was the most frequently used regimen in patients with an estimated glomerular filtration rate < 60 ml/min/1.73 m(2) and in those with estimated glomerular filtration rate ≥ 60 ml/min/1.73 m(2). The gemcitabine and cisplatin patients' complete response rate was 10.5% and their response rate was 52.4%, which was highest among all regimens. Gemcitabine and cisplatin demonstrated a better 3-year overall survival when the estimated glomerular filtration rate was ≥ 60 ml/min/1.73 m(2) (31.4%), but it tended to be worse when the estimated glomerular filtration rate was < 60 ml/min/1.73 m(2) (14.1%). In the latter cases, the dose reduction rate of gemcitabine and cisplatin was high (43.9%). Among the patients with estimated glomerular filtration rate < 60 ml/min/1.73 m(2), the 1-year overall survival of the patients treated with a reduced dose of gemcitabine and cisplatin was significantly lower than that of those treated with standard-dose gemcitabine and cisplatin (26.2 vs. 60.3%, respectively, P = 0.0108)., Conclusions: Gemcitabine and cisplatin provided favorable responses and survival in patients with estimated glomerular filtration rate ≥ 60 ml/min/1.73 m(2) but unsatisfactory oncological outcomes in patients with estimated glomerular filtration rate < 60 ml/min/1.73 m(2), especially when treated with a reduced dose. Alternative regimens might be optimal rather than reduced-dose gemcitabine and cisplatin in patients with estimated glomerular filtration rate < 60 ml/min/1.73 m(2)., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A 39-year-old man visited our clinic with gross hematuria. Cystoscopy revealed a papillary tumor at the urinary bladder dome. Abdominal magnetic resonance imaging (MRI) and computed tomography(CT) demonstrated a tumor extending from the umbilicus to the bladder dome. Transurethral resection of bladder tumor (TUR-Bt) was performed and histopathological findings revealed adenocarcinoma. Chest CT and examination of the upper gastrointestinal did not reveal any abnormal findings. The tumor was diagnosed as stage IIIA urachal carcinoma, and en bloc segmental resection was performed. About 10 months later, chest CT demonstrated multiple lung metastases. After two courses of combination chemotherapy with methotrexate (MTX), 5-fluorouracil (5-FU), epirubicin (epiADM), and cisplatin (CDDP), the multiple lung metastases completely disappeared. The patient has survived 23 months to date with no evidence of disease and is receiving adjuvant chemotherapy with tegafur uracil.

A 59-year-old man diagnosed with Stage IV advanced gastric cancer due to pancreatic invasion(T4)and splenic hilum lymph node metastasis(N3)was initially treated with neoadjuvant chemotherapy using S-1 and CDDP. However, it was discontinued because the tumor marker increased after 1 course. Instead of S-1 and CDDP, S-1 and paclitaxel were then administered. After 4 courses, CT scan revealed reduced tumor size and the disappearance of splenic hilum lymph node swelling that indicated PR of the chemotherapy. Moreover, serum CEA was remarkably decreased to 77 ng/mL from 1,092 ng/mL. He could undergo subtotal gastrectomy(Billroth II)with lymph node dissection(D2)and cholecystectomy. Histopathological examination revealed Stage II (pT2(SS), pN1, CY0, ly1, v2)advanced gastric cancer that showed good effect of S-1 and paclitaxel. At this writing (October 2007), the patient has remained free of disease for more than 1 year and 6 months with good nutrition. Neoadjuvant chemotherapy using S-1 and paclitaxel for advanced gastric cancer seems to have been effective.

Purpose: Only 20-30% of patients with cisplatin refractory or relapsed germ cell cancer will remain continuously disease free with salvage chemotherapy. Paclitaxel is a potent anticancer agent against a variety of solid cancers. The present study investigated the chemotherapy with paclitaxel in combination with nedaplatin, which is a derivative of cisplatin, and ifosphamide as salvage chemotherapy for cisplatin refractory germ cell cancer., Material and Methods: The combination chemotherapy consisted of paclitaxel 210 mg/m2 on day 1, nedaplatin 100 mg/m2 on day 2 and ifosphamide 1.2 g/m2 on day 2-day 6 every three weeks. Fourteen patients with cisplatin refractory germ cell cancer, ranging in age from 17 to 44 years were enrolled onto the study., Results: Fourteen patients were evaluated for response and toxicity. Patients received 1-14 cycles of the combination chemotherapy. The median duration of follow-up was 34 months (10-64 months). Response rate was 57.1% (CR / PR(m-):8 cases, NC:5 cases, PD:1 cases). Seven patients remain alive without disease. However, 5 patients died of the disease. All patients had grade 3 or 4 hematological toxicity., Conclusion: This study demonstrates that the chemotherapy with paclitaxel in combination with nedaplatin and ifosphamide showed a significant anticancer activity for patients with cisplatin refractory or relapsed germ cell cancer. These findings suggest that the combination chemotherapy may be one of the options of salvage chemotherapy for cisplatin refractory or relapsed germ cell cancer.

Approximately 80% of patients with metastatic testicular tumors are cured by cisplatin-containing chemotherapy and surgery. However, the remaining 20% of patients with advanced testicular tumors can not be cured at present. Thus, therapy for these testicular tumors infractory to treatment is the most important issue. Recently, chemotherapy for such tumors is developing, especially salvage chemotherapy using novel anticancer agents(paclitaxel, gemcitabine,irinotecan, docetaxel, oxaliplatin, etc) and high-dose anticancer drugs. Some of the new modalities are very attractive. In this article, we reviewed mainly these new forms of chemotherapy for testicular tumors.

Background: Only 20-30% of patients with refractory or recurrent germ cell tumors (GCT) are cured by salvage chemotherapy. Irinotecan, a new derivative of camptothecin, is a potent anticancer agent against a variety of solid cancers. The current pilot study investigated the efficacy of salvage chemotherapy with irinotecan in combination with cisplatin (CDDP) or nedaplatin (NDP), a derivative of cisplatin, for GCT., Methods: The combination chemotherapy consisted of 100-150 mg/m(2) irinotecan on Days 1 and 15 or 200-300 mg/m(2) on Day 1 in combination with 20 mg/m(2) CDDP on Days 1-5 or 100 mg/m(2) NDP on Day 1 every 4 weeks. Patients with refractory GCT, ranging in age from 17 to 43 years, received 2-11 cycles of the combination chemotherapy. The median duration of follow-up is 28 months (8-140 months)., Results: Twenty patients entered this study, 18 of whom were assessed for response and toxicity. The response rate was 50 % (two complete responses and seven partial responses). Nine patients remain alive without disease. However, six patients died of the disease and one patient died of a brain glioma. The 5-year survival rate was approximately 53%. Myelosuppression was the major toxicity, but was manageable., Conclusions: This pilot study demonstrates that the chemotherapy with irinotecan in combination with CDDP or NDP showed significant anticancer activity for patients with refractory GCT, without serious side effects. Although this study comprised only a few patients, these findings suggest that the combination chemotherapy may be one of the options of salvage chemotherapy for patients with refractory GCT., (Copyright 2002 American Cancer Society.)

A study to evaluate the efficacy of cisplatin, doxorubicin, and etoposide chemotherapy with combined radiotherapy was undertaken in 26 patients with limited disease-small-cell lung cancer. Patients were treated with cisplatin (80 mg/m2) intravenously (i.v.) on day 1, doxorubicin (30 mg/m2) i.v. on day 1, and etoposide (80 mg/m2) i.v. on days 1, 3, and 5, every 4 weeks for four cycles. Thoracic irradiation of 40 Gy in 20 fractions was delivered during 4 weeks to the primary site starting on day 8 of the second cycle of chemotherapy. The objective response rate was 100%. A complete response was observed in 10 patients (38%). The median survival time was 23 months, and the 3-year survival rate was 42%. Seven patients (27%) continued to survive at least 8 years and remain free from disease. Grade III/IV leukopenia was observed in 25 patients (96%). Grade III/IV thrombocytopenia developed in 19 patients (73%). Grade III/IV esophagitis was not seen. Interstitial pneumonitis occurred in two patients. This regimen is effective and has acceptable toxicity for use in the treatment of limited disease-small-cell lung cancer.

Between 1982 and 1991, 24 patients with advanced testicular germ cell tumor were treated by combination chemotherapy with cisplatin, vinblastine and bleomycin (PVB). Based on short-term efficacy of the PVB regimen and long-term prognosis in our patients, we evaluated 4 risk criteria proposed by Indiana University, National Cancer Institute (NCI), Memorial Sloan-Kettering Cancer Center (MSKCC) and European Organization for Research and Treatment of Cancer (EORTC). Clinical staging were IIA in 8 patients, IIB in 8, IIIA in 1, IIIB in 5 and IIIC in 2. Metastases included retroperitoneal lymph node in 20 cases (> 5 cm in 10), lung in 6, bone and liver in each 1. Complete response (CR) was obtained in 12 (50%) patients and partial response (PR) in 9 (38%). According to the stage and metastatic site, CR was achieved in 75%, 38% and 38%of the stage IIA, IIB and III tumors, respectively, and in 60% and 50% of retroperitoneal and pulmonary metastases, respectively. However, neither CR nor PR was recognized for live and bone metastases. Prognosis was assessed with a mean followup period of 88.5 months. Although all 12 patients with CR were alive, 4 of the 9 with PR and all patients on whom the drug was ineffective died of cancer. Accuracy in predicting prognosis was 82%, 75%, 74%, and 63% using the MSKCC, Indiana, NCI and EORTC risk criteria, respectively.

It is reported that the combination of cisplatin (CDDP) and carboplatin (CBDCA) is synergistic in vitro. The objective of this study was to evaluate the therapeutic effect and safety of the two platinum compounds in combination with etoposide in the treatment of non-small-cell lung cancer (NSLC). Forty patients were registered. Based on the results of a phase I study, patients were treated with CDDP (80 mg/m2 i.v. on day 1), CBDCA (280 mg/m2 i.v. on day 1), and etoposide (80 mg/m2 i.v. on days 1-3). Of the 40 patients, 30 were men and 10 women. Histology revealed adenocarcinoma(AC) (n = 20), squamous cell carcinoma(SCC) (n = 18), and large cell carcinoma(LCC) (n = 2). Staging: IIIA (n = 3); IIIB (n = 17); and IV (n = 20). A 32.5% overall response rate [13 of 40; 95% confidence interval (CI) 18-47%] was achieved. The response rates in patients with SCC and AC were 55.6 and 10.0% (p < 0.005), respectively. The median duration of response was 47.1 weeks and the overall median survival time was 57.1 weeks. Leukopenia and thrombocytopenia--World Health Organization (WHO) grade IV--occurred in nine and 11 patients, respectively. Nonhematological toxicities were mainly nausea, vomiting, and alopecia. In conclusion, further investigations of this regimen are warranted in the treatment of NSLC.

Cisplatin (CDDP)-containing chemotherapy has become the mainstay of clinical trials in unresectable non-small-cell lung cancer (NSCLC), but the role of chemotherapy in the routine management of NSCLC remains controversial. We conducted a phase I study with the combination carboplatin (CBDCA), CDDP, and etoposide (Etop) in unresectable NSCLC. CBDCA, at a starting dose of 80 mg/m2, on day 1, was combined with a fixed dose of CDDP (80 mg/m2, day 1) and Etop (80 mg/m2, days 1-3). Escalation was performed after four patients entered at each dose level. If no World Health Organization (WHO) grade 4 toxicity developed after the first cycle in more than half of the patients or WHO grade 3/4 toxicity in more than two thirds, the dose was escalated. The maximum tolerated dose was established at 300 mg/m2 for CBDCA. Thrombocytopenia and leukopenia were the dose-limiting toxicities. No grade 3/4 nonhematologic toxicities were seen. The recommended dose of CBDCA to be combined with CDDP (80 mg/m2, day 1) and Etop (80 mg/m2, days 1-3) is 280 mg/m2. This trial suggests that our combination chemotherapy may be effective in patients with advanced NSCLC. A multicenter phase II study based on these findings is now under way.