A randomized phase II study of irinotecan plus cisplatin versus irinotecan plus capecitabine with or without isosorbide-5-mononitrate in advanced non-small-cell lung cancer

BackgroundWe investigated the efficacy of irinotecan/cisplatin (IP) versus irinotecan/capecitabine (IX) with or without isosorbide-5-mononitrate (ISMN) in chemo-naïve advanced non-small-cell lung cancer.Patients and methodsInitially, 74 patients were randomly assigned to either IP or IX. Given the potential benefits of ISMN on chemotherapy, the protocol was amended during the study. Subsequently, 72 patients were randomly assigned to either IP + ISMN or IX + ISMN. Patients were treated with predefined second-line therapies (docetaxel/capecitabine for IP or IP + ISMN, docetaxel/cisplatin for IX or IX + ISMN) when disease progressed.ResultsA total of 146 received treatment. Response rate (RR), median progression-free survival (PFS) and overall survival (OS) were 49%, 5.5 months, 14.5 months in IP; 33%, 3.3 months, 13.0 months in IP + ISMN; 30%, 4.3 months, 16.1 months in IX; and 25%, 3.4 months, 13.6 months in IX + ISMN, respectively. While IP arm showed a trend toward higher RR and longer PFS than IX arm, IX arm showed a trend toward longer OS than IP arm. No significant differences were observed between IP + ISMN and IX + ISMN.ConclusionIP showed better RR and PFS but no OS benefit when compared with IX. The addition of ISMN to IP or IX chemotherapy did not seem to improve the treatment outcome.     

Phase II study of weekly docetaxel combined with cisplatin in patients with advanced non-small-cell lung cancer

Purpose To evaluate the safety and efficacy of the combination of cisplatin on day 1 and docetaxel on days 1, 8 and 15 every 4 weeks for the treatment of previously untreated patients with non-small-cell lung cancer (NSCLC).Patients and methods A group of 38 patients with advanced or metastatic NSCLC who had not received prior treatment and who were aged under 75 years were enrolled. The patients received intravenous infusions of docetaxel (25 mg/m², days 1, 8, 15) and cisplatin (80 mg/m², day 1), followed by a week of rest.Results Six patients had grade 3/4 neutropenia (18%), but there were no episodes of neutropenic fever. Nonhematologic toxicities were also mild. There were 12 partial responses for an objective response rate of 31.6%. The median survival was 11.8 months, and the 1-year survival rate was 46.5%.Conclusion Cisplatin combined with weekly administration of docetaxel is efficacious against NSCLC with low hematotoxicity, and this schedule may be an alternative for the treatment of NSCLC.     

Phase II trial of weekly irinotecan plus cisplatin in advanced esophageal cancer.

PURPOSE: To evaluate the response, toxicity, survival, and quality of life in patients with unresectable or metastatic esophageal cancer treated with weekly irinotecan and cisplatin. PATIENTS AND METHODS: Thirty-five patients with metastatic or unresectable esophageal adenocarcinoma (23 patients) or squamous cell carcinoma (12 patients) were treated. No prior chemotherapy was allowed. The majority of patients had metastatic and bidimensionally measurable disease (34 patients each [97%]). Patients were treated with cisplatin 30 mg/m(2) and irinotecan 65 mg/m(2), repeated weekly for 4 weeks, followed by a 2-week rest period. Treatment was recycled every 6 weeks. Degree of dysphagia relief was monitored, and quality of life was measured prospectively using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 and Functional Assessment of Cancer Therapy-General instruments. RESULTS: Thirty-five patients were assessable for response and toxicity. Major objective responses were observed in 20 patients (57%; 95% confidence interval, 41% to 73%), including two complete responses (6%). Similar response rates were observed for adenocarcinoma (12 of 23 patients; 52%) and squamous carcinoma (eight of 12 patients; 66%). The median duration of response was 4.2 months (range, 1 to 8.8+ months). Median actuarial survival was 14.6 months (range, 1 to 15.2+ months). In 20 patients with dysphagia assessable at baseline, 18 (90%) noted either improvement or resolution of dysphagia on chemotherapy. Global quality of life improved in responding patients, primarily because of improvements in pain, emotional state, and relationships with family and friends. Toxicity was relatively mild and included only three patients (9%) with grade 4 neutropenia and four (11%) with grade 3 diarrhea. There were no treatment-related deaths. CONCLUSION: The combination of weekly cisplatin plus irinotecan had significant activity in metastatic esophageal carcinoma and resulted in significant relief of dysphagia. The regimen was well tolerated, with acceptable myelosuppression and rare treatment-related diarrhea. Further evaluation of the combination of weekly irinotecan and cisplatin, including the addition of other agents to this regimen, is indicated.     

Phase I study of docetaxel and irinotecan in patients with advanced non-small-cell lung cancer

The role of non-platinum combination chemotherapy in the treatment of advanced non-small-cell lung cancer (NSCLC) has not yet been clarified. In this phase I study, the dose-limiting toxicity (DLT), the maximum tolerable dose (MTD) and the antitumor activity of a two-drug combination of docetaxel (DCT) and irinotecan (CPT) in patients with advanced NSCLC were evaluated. Previously untreated patients with NSCLC in stage IIIB with malignant pleural effusion or stage IV were eligible. Both drugs were administered by 1-h intravenous infusion on day 1, and repeated every 3 weeks. DCT was given before CPT administration. Five escalating dose levels of DCT/CPT (40/135, 50/135, 50/150, 60/150, and 60/165 mg/m2) were studied. Eighteen patients received 44 courses. The DLT was considered to be neutropenia, because grade 4 neutropenia lasting for 3 days or more was observed in three patients, which was accompanied with three episodes of febrile neutropenia. As a non-hematological toxicity, grade 3 diarrhea occurred in three patients. Since all the three patients treated at the fifth dose level (DCT at 60 mg/m2 and CPT at 165 mg/m2) experienced DLT (grade 4 neutropenia in two patients and grade 3 hepatic toxicity in one), this dose level was determined to be the MTD. The objective response rate was 33.3%, and the median survival time was 13.6 months. To confirm the effectiveness of this combination for advanced NSCLC which was suggested in the present study, a phase II study with the recommended doses (150 mg/m2 for CPT and 50-60 mg/m2 for DCT) is warranted.     

Phase II study of irinotecan plus cisplatin with concurrent radiotherapy for the patients with limited-disease small-cell lung cancer

BACKGROUND: A recently conducted randomized, phase III study that compared irinotecan plus cisplatin (IP) with etoposide plus cisplatin for the patients with extensive disease SCLC revealed a superior median survival rate and a superior 2-year survival rate for the IP combination therapy. Yet there have been few such reports on the patients suffering with limited disease SCLC (LD-SCLC). We conducted a phase II trial to evaluate the efficacy and toxicity of administering IP with concurrent radiotherapy for the patients with LD-SCLC. PATIENTS AND METHODS: Twenty chemotherapy-na?ve patients with LD-SCLC were enrolled in our study. The patients were treated with 40 mg/m(2) irinotecan on days 1, 8 and 15 and with 60 mg/m(2) cisplatin on day 1 every 4 weeks until a maximum of six cycles was delivered. Once-daily radiotherapy included the administration of 50.4 Gy in 28 fractions. After completion of the radiation therapy, the dose of irinotecan was increased to 60 mg/m(2). RESULTS: The response rate was 85% (CR: 6; partial response, PR: 11). The median survival was 20.0 months (95% CI: 15.6-24.4 months) with 1-year and 2-year overall survival rates of 85 and 35%, respectively. The median progression free survival (PFS) was 12 months (95% CI: 6.2-18.1 months) with a 1-year PFS of 36%. The major hematologic toxicities of this regimen were neutropenia (60%), leukopenia (55%), anemia (20%) and thrombocytopenia (10%). The non-hematologic toxicities were nausea/vomiting (55%), diarrhea (35%) and dysphagia (15%). CONCLUSIONS: Our data show that IP with concurrent radiotherapy is an effective and tolerable regimen for the treatment of LD-SCLC and these findings warrant further investigation.     

A phase II study of paclitaxel plus cisplatin for advanced non-small-cell lung cancer in Japanese patients

We performed a clinical phase II trial of the combination of paclitaxel and cisplatin in patients with locally advanced (stage IIIB) or metastatic non-small-cell lung cancer (NSCLC) using a 3-h infusion of paclitaxel followed by a 1 to 2-h infusion of cisplatin, with a short premedication regimen. Treatment was repeated every 21 days for at least two cycles. The patients received paclitaxel 180 mg/m2 followed by cisplatin 80 mg/m2. Enrolled in the trial were 33 chemotherapy-naive patients with stage IIIB (15%) or stage IV (85%) NSCLC. Their median age was 61 years (range 43-71 years). Of the 33 patients, 10 (30%) were women and 23 (70%) were men, and 82% had adenocarcinoma. With 78 courses of chemotherapy administered, 32 patients were evaluable for toxicity and response. Hematologic toxicities were moderate: Japan Clinical Oncology Group (JCOG) grade 3 or 4 neutropenia occurred in 37% of the cycles (53% of patients). Other toxicities consisted mainly of grade 1 or 2 alopecia and nausea/vomiting, but also included grade 1 or 2 neuropathy (47%), hypotension (grade 1 in 6%, grade 3 in 3%) and allergic reactions (grade 1 or 2 in 16%, grade 3 in 3%). Of 32 patients evaluable for response, a partial response was achieved in 10 (31%; 95% confidence interval 16% to 50%), stable disease was seen in 16 (50%), and disease progression was seen in 2 (6%). The median survival time was 14.8 months and the 1-year survival rate was 56%. These results suggest that the combination of paclitaxel and cisplatin is a well-tolerated and active regimen in Japanese patients with advanced NSCLC. In view of the promising survival outcomes, further evaluation in prospective randomized trials with other regimens is warranted.     

Second-line treatment with irinotecan plus cisplatin vs cisplatin of patients with advanced non-small-cell lung cancer pretreated with taxanes and gemcitabine: a multicenter randomised phase II study

The aim of this study was to compare the irinotecan/cisplatin regimen with cisplatin as second-line chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) pretreated with a taxane/gemcitabine regimen. Patients (n = 147) with stage IV NSCLC pretreated with a taxane/gemcitabine regimen were randomly assigned to receive either irinotecan (110 mg m(-2), day 1 and 100 mg m(-2), day 8) and cisplatin (80 mg m(-2), day 8) (IC; n = 74) or CDDP (80 mg m(-2), day 1) (C; n = 73) every 3 weeks. Patients treated with IC and C had a median survival of 7.8 and 8.8 months, respectively (P = 0.933). The 1-year survival rate was 34.3% for IC-treated patients and 31.7% for C-treated patients. Cox's regression analysis revealed that response to treatment (hazard ratio (HR) = 2.787; 95% confidence interval (CI): 1.1578-4.922) and performance status (HR = 1.865; 95% CI: 1.199-2.872) was independent prognostic factors for survival. Overall response rate was 22.5% (95% CI: 12.8-32.2%) for IC-treated patients and 7.0% (95% CI: 1.15-13.6%) for C-treated patients (P = 0.012); tumour growth control (partial remission (PR) + stable disease (SD)) was observed in 26 (38%) IC and 25 (36%) C patients (P = 0.878). There was no difference in terms of quality of life between the two chemotherapy arms. The incidence of febrile neutropenia, grade 3 and 4 neutropenia and grade 3 and 4 diarrhoea was significantly higher in the IC- than the C-treated patients. Other toxicities were mild. There were no treatment-related deaths in either arm. The IC regimen did not confer a survival benefit compared with C as second-line treatment of patients with advanced NSCLC pretreated with a taxane/gemcitabine regimen, despite its better efficacy in terms of response rate.     

NP方案与TP方案治疗晚期非小细胞肺癌临床分析

目的评价NP方案、TP方案治疗晚期非小细胞肺癌的疗效和毒副反应.方法 NP方案:长春瑞滨(NVB) 25 mg/m2,快速静脉滴注,第1、8天;顺铂(PDD)45 mg/m2,静脉点滴,第1～2天.TP方案:紫杉醇(PTX)135 mg/m2,静脉点滴,第1天,持续3 h;PDD 80 mg/m2,静脉点滴,第2天.21 d为一周期.结果 NP组30例,CR 2例(6.7%),PR 12例(40.0%),SD 12例(40.0%),总有效率46.7%;TP组29例,CR 1例(3.4%),PR 12例(41.4%),SD 11例(37.9%),总有效率44.8%.NP组和TP组中位缓解时间分别为5.5个月和4.5个月.初治优于复治(NP组为72.7%对31.6%,P=0.0308;TP组为75.0%对33.3%,P=0.0480);Ⅲb期优于Ⅳ期(NP组为77.8%对33.3%,P=0.0288;TP组为85.7%对31.8%,P=0.0176).剂量限制性毒性主要为骨髓抑制,NP组较TP组稍重,白细胞、血小板减少发生率分别为66.7%、51.7%和33.3%、31.0%.TP组脱发、周围神经毒性/疼痛较NP组重,而NP组静脉炎及胃肠道反应较TP组重.无Ⅳ度反应出现,患者均能够较好地耐受,不影响化疗继续进行.结论 NP方案、TP方案治疗晚期非小细胞肺癌安全有效,既可用作一线方案,也可用作二线方案,且二者无明显交叉耐药性,可互为挽救方案.     

吉西他滨联合顺铂或卡铂治疗晚期非小细胞肺癌的近期疗效

目的 :观察吉西他滨 (gemcitabine)联合顺铂与吉西他滨联合卡铂治疗晚期非小细胞肺癌的疗效和毒性反应。方法 :10 6例经病理组织学或细胞学证实的晚期非小细胞肺癌患者分为GP和GC两组 ,GP组应用吉西他滨 10 0 0mg/m2 ,静滴 ,第 1、8天 ;顺铂 30mg/m2 ,静滴 ,第 1～ 3天。GC组应用吉西他滨 10 0 0mg/m2 ,静滴 ,第 1、8天 ;卡铂ACU =5 ,静滴 ,第 1天。 2 1天为 1个周期 ,连用 2个周期评价疗效。结果 :GP组和GC组有效率 (CR PR)分别为 4 8.1%和 4 4 .2 % (P >0 .0 5 ) ;中位疾病进展时间分别为 6 .8个月和 6 .2个月 (P >0 .0 5 ) ;毒性反应中GP组消化道毒副反应较GC组大 ,差异有显著性 ;骨髓毒性两组相当 ,差异无显著性。结论 :吉西他滨联合顺铂及吉西他滨联合卡铂两方案治疗晚期非小细胞肺癌疗效均较好 ,毒性反应轻微 ,患者耐受良好 ,尤其吉西他滨联合卡铂的消化道反应轻 ,患者易于接受 ,值得临床进一步研究。     

Phase II study of nedaplatin and irinotecan with concurrent thoracic radiotherapy in patients with locally advanced non-small-cell lung cancer

Background:

Current international guidelines recommend the use of platinum-based chemotherapy with thoracic radiotherapy (TRT) for patients with locally advanced non-small-cell lung cancer (NSCLC).

Methods:

Patients with unresectable stage IIIA or IIIB NSCLC were treated with nedaplatin (NP) at 50 mg m⁻² and irinotecan (CPT) at 60 mg m⁻² on days 1 and 8 every 4 weeks for two to four cycles with concurrent TRT (2 Gy per day, total 60 Gy).

Results:

All 35 patients were able to receive a total of 60 Gy. Adverse effects and events in chemotherapy with TRT were grade 3 or 4 anaemia, neutropenia and thrombocytopenia, which occurred in 3.0%, 32.8% and 6.0% of patients, respectively. There was no grade 3 pneumonitis or oesophagitis. Adverse effects and events in chemotherapy alone were mild. There was no treatment-related death. An overall response rate was 94.3%. The median progression-free and overall survivals were 13.0 and 36.0 months, respectively. The 5-year disease-free and overall survival rates were 25.7% and 40.0%, respectively.

Conclusion:

NP and CPT treatment with concurrent TRT is effective and safe for patients with unresectable, locally advanced NSCLC.     

Phase I/II study of cisplatin combined with weekly paclitaxel in patients with advanced non-small-cell lung cancer

To determine the maximum-tolerated dose (MTD) and the recommended dose (RD) of paclitaxel administered weekly with a fixed dose of cisplatin, and to assess the toxicity and activity of this combination, we conducted a phase I/II trial in patients with advanced non-small-cell lung cancer (NSCLC). In this study, patients with stage IIIB/IV NSCLC were eligible. Paclitaxel, at a starting dose of 40 mg x m(-2) week(-1) on days 1, 8, and 15, was combined with a fixed dose of cisplatin 80 mg x m(-2) on day 1. Chemotherapy was given in a 4-week cycle. In this phase I/II study, 38 patients were enrolled. Dose-limiting toxicities (DLT) were neutropenia, fatigue, and omission of treatment due to leucopenia, thrombocytopenia, or febrile neutropenia. The MTD and RD were estimated to be 70 mg x m(-2). Of the 37 assessable patients, 23 had a partial response and one had a complete response. Overall response rate was 62.1% (95% confidence interval (CI): 46.5-77.7%). The progression-free survival, the median survival time, and the 1-year survival rate were 5.5 months, 13.7 months, and 56.9%, respectively. This regimen is tolerable and very active against advanced NSCLC, and its efficacy should be confirmed in a phase III study.     

Phase II and pharmacologic study of weekly oral paclitaxel plus cyclosporine in patients with advanced non-small-cell lung cancer.

PURPOSE: A phase II study was performed to assess the efficacy and toxicity of oral cyclosporine (CsA) plus paclitaxel in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive or previously treated patients (one regimen) with measurable disease and World Health Organization performance status 相似文献   

Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer.

PURPOSE: The Hoosier Oncology Group has previously reported the results of its phase II trial of the combination of cisplatin plus gemcitabine. In that study of 27 assessable patients with advanced or metastatic non-small-cell lung cancer (NSCLC), the response rate was 33%, with a median survival of 8.4 months. Based on such favorable results, the Hoosier Oncology Group designed this randomized phase III study of gemcitabine plus cisplatin compared with cisplatin alone in chemotherapy-naive patients with advanced NSCLC. PATIENTS AND METHODS: Patients were randomized to receive either cisplatin (100 mg/m(2) intravenously on day 1 of a 28-day cycle) or the combination of cisplatin (100 mg/m(2) intravenously on day 1) plus gemcitabine (1,000 mg/m(2) administered intravenously on days 1, 8, and 15 of a 28-day cycle). RESULTS: From August 1995 to February 1997, 522 assessable chemotherapy-naive patients were randomized. Toxicity was predominantly hematologic and was more pronounced in the combination arm, with grade 4 neutropenia occurring in 35.3% of patients compared with 1.2% of patients on the cisplatin monotherapy arm. The incidence of neutropenic fevers was less than 5% in both arms. Grade 4 thrombocytopenia occurred in 25. 4% of patients on the combination arm compared with 0.8% of patients on the cisplatin monotherapy arm. No serious hemorrhagic events related to thrombocytopenia were reported for either arm. The combination of gemcitabine plus cisplatin demonstrated a significant improvement over single-agent cisplatin with regard to response rate (30.4% compared with 11.1%, respectively; P <.0001), median time to progressive disease (5.6 months compared with 3.7 months, respectively; P =.0013), and overall survival (9.1 months compared with 7.6 months, respectively; P =.004). CONCLUSIONS: For the first-line treatment of NSCLC, the regimen of gemcitabine plus cisplatin is superior to cisplatin alone in terms of response rate, time to disease progression, and overall survival.     

Cost-effectivenes of paclitaxel plus cisplatin in advanced non-small-cell lung cancer.

The aim of this study was to assess the cost-effectiveness of combination chemotherapy with paclitaxel/cisplatin, compared with standard etoposide/cisplatin in patients with advanced non-small cell lung cancer (NSCLC). We obtained the primary survival and resource utilization data from a large three-arm randomized trial comparing: paclitaxel 135 mg m(-2) by 24-h intravenous (i.v.) infusion + cisplatin; paclitaxel 250 mg m(-2) by 24-h i.v. infusion + cisplatin + granulocyte colony-stimulating factor (G-CSF); and standard etoposide/cisplatin in patients with stage IIIb or IV NSCLC. We also modelled the regimens with paclitaxel 135 mg m(-2) + cisplatin administered as an outpatient by 3-h infusion, as clinical data suggest that this is equivalent to 24-h infusion. We collected costing data from the Ottawa Regional Cancer Centre and applied it to the resources consumed in the randomized trial. We integrated these data into the Statistics Canada POpulation HEalth Model (POHEM), which generated hypothetical cohorts of patients treated with each regimen. The POHEM model assigned diagnostic work-up, treatment, disease progression and survival characteristics to each individual in these cohorts and tabulated the costs associated with each. We did sensitivity analyses around the costs of chemotherapy and its administration, and the survival differences between the two regimens. All costs are in 1997 Canadian dollars ($1.00 Canadian approximately Pound 0.39 sterling). The perspective is that of the Canadian health care system. In the trial, the two paclitaxel-containing arms had almost identical survival curves with a median survival of 9.7 months compared with 7.4 months for etoposide/cisplatin. As administered in the trial, paclitaxel/cisplatin cost $76,370 per life-year gained (LYG) and paclitaxel/cisplatin/G-CSF $138,578 per LYG relative to etoposide/cisplatin. However, when modelled as an outpatient 3-h infusion, paclitaxel/cisplatin was moderately cost-effective at $30,619 per LYG. When compared with historical controls treated with best supportive care, this regimen of paclitaxel/cisplatin cost $4539 per LYG. Assuming a 3-h paclitaxel infusion yields the same survival advantage as the 24-h infusion did in the randomized trial, paclitaxel/cisplatin is a cost-effective improvement over standard etoposide/cisplatin for patients with advanced non-small cell lung cancer.     

Phase II study of cisplatin continuous infusion plus vindesine in the treatment of non-small-cell lung cancer.

We administered chemotherapy consisting of a combination of 5-day continuous intravenous infusion of cisplatin (25 mg/m2/day) plus vindesine (3 mg/m2, as a bolus, on days 1 and 8) to 30 patients with advanced non-small-cell lung cancer (NSCLC) and examined the effectiveness and safety of the treatment. Fifteen patients achieved a partial response, and the overall response rate was 50%, with a median response duration of 30.1 weeks (range 5-108.6 weeks) and a median survival of 39 weeks. Observed side effects were leukopenia (less than 3000/mm3) in 90% of patients (including less than 1000/mm3 in 23%), thrombocytopenia (less than 75000/mm3) in 30%, anemia (hemoglobin less than 9.5 g/dl) in 50%, vomiting in 43%, and alopecia in 77%. Elevated serum creatinine was not seen, and there were no treatment-related deaths. Toxicity was quite acceptable, but hematological toxicity was increased, and treatment was delayed for six patients because of leukopenia. We conclude that this regimen is generally well tolerated in patients with advanced NSCLC. Further studies in which the optimum therapeutic schedule can be made sufficiently safe to reduce leukopenia are needed.     

Phase II study of the combination of vinorelbine and cisplatin in advanced non-small-cell lung cancer

Purpose To evaluate the efficacy and safety of combination chemotherapy with cisplatin and vinorelbine for the treatment of previously untreated patients with advanced non-small-cell lung cancer (NSCLC).Patients and methods Eligible patients were those with measurable NSCLC. They were treated with two or more cycles of a regimen consisting of vinorelbine 25 mg/m² on days 1 and 8 and cisplatin 80 mg/m² on day 1 every 3 weeks.Results A total of 45 patients were enrolled. The response rate was 51.1% (23/45; 95% CI 35.8% to 66.3%). The median survival was 286 days with a 1-year survival rate of 40%. The median number of treatment cycles was 2. The major toxic effect was neutropenia of grade 3 or higher (84%). Nonhematological toxicities, including vomiting (62%), were mild (grade 2 or less). There were no treatment-related deaths.Conclusion The high response rate and good tolerability proved this combination therapy to be a safe and effective treatment for advanced NSCLC.This work was supported in part by a grant-in-aid from the Ministry of Health and Welfare (Tokyo, Japan) and from the Second Term Comprehensive 10-Year Strategy for Cancer Control.     

Phase II multicentre study of docetaxel plus cisplatin in patients with advanced urothelial cancer

A multicentre phase II trial was undertaken to evaluate the activity and toxicity of docetaxel plus cisplatin as first-line chemotherapy in patients with urothelial cancer. Thirty-eight patients with locally advanced or metastatic transitional-cell carcinoma of the bladder, renal pelvis or ureter received the combination of docetaxel 75 mg m(-2) and cisplatin 75 mg m(-2) on day 1 and repeated every 21 days, to a maximum of six cycles. The median delivered dose-intensity was 98% (range 79-102%) of the planned dose for both drugs. There were seven complete responses and 15 partial responses, for and overall response rate of 58% (95% CI, 41-74%). Responses were even seen in three patients with hepatic metastases. The median time to progression was 6.9 months, and the median overall survival was 10.4 months. Two patients who achieved CR status remain free of disease at 4 and 3 years respectively. Grade 3-4 granulocytopenia occurred in 27 patients, resulting in five episodes of febrile neutropenia. There was one toxic death in a patient with grade 4 granulocytopenia who developed acute abdomen. Grade 3-4 thrombocytopenia was rare (one patient). Other grade 3-4 toxicities observed were anaemia (three patients), vomiting (five patients), diarrhoea (four patients), peripheral neuropathy (two patients) and non-neutropenic infections (seven patients). Docetaxel plus cisplatin is an effective and well-tolerated regimen for the treatment of advanced urothelial cancer, and warrants further investigation.