A pilot study of gemcitabine in combination with oxaliplatin and vinorelbine in patients with metastatic bladder cancer.

AIM: To assess the safety and to obtain preliminary data on the efficacy of the three-drug combination chemotherapy with gemcitabine, oxaliplatin and vinorelbine in patients with metastatic bladder cancer. PATIENTS AND METHODS: Patients with metastatic or locally unresectable advanced bladder cancer who had received either no or one previous systemic chemotherapy regimen were eligible. All patients received intravenous gemcitabine 700 mg/m(2) and vinorelbine 25 mg/m(2) on day 1, then intravenous oxaliplatin 85 mg/m(2) on day 2, every 14 days. RESULTS: Fifteen patients were enrolled. Twelve patients were unfit for cisplatin. A median of five cycles per patient were delivered. The most common toxicities were neutropenia, nausea and vomiting, mucositis and diarrhoea. Two complete responses and one partial response were observed for an overall response rate of 23%. Median progression-free survival was 5.7 months and overall survival was 8.6 months. CONCLUSION: Although active and tolerable, the described three-drug combination chemotherapy showed no obvious incremental increase in efficacy compared with two-drug regimens. Further clinical trials are not recommended.

[What is the objective of second-line chemotherapy after failure of first-line chemotherapy in hormone-resistant metastatic prostate?]. / Chimiothérapie de deuxième ligne après échec d'une chimiothérapie de première ligne dans le cancer de la prostate métastatique hormono-résistant. Pour quel objectif?

UNLABELLED: Chemotherapy occupies an increasingly important place in the management of hormone-resistant metastatic prostate cancer. For the first time in this disease, docetaxel increases the survival of patients, with a modest, but definite median gain of about 2 months. In everyday practice, the indication for second-line chemotherapy after immediate or delayed failure of first-line chemotherapy is sometimes considered, although objective data concerning its efficacy are limited. The objective of the present study was to retrospectively evaluate the results obtained with second-line chemotherapy in a patient cohort managed at the Montpellier Regional Cancer Centre. PATIENTS AND METHODS: Clinical characteristics, treatments delivered and outcome of 43 patients who received two successive lines of chemotherapy were retrospectively collected by means of a standardized questionnaire. Three groups of patients were defined as a function of the chemotherapy protocols delivered: docetaxel alone or in combination, mitoxantrone and other protocols not comprising either docetaxel or mitoxantrone. Responses to chemotherapy were analysed according to three criteria: objective responses, laboratory responses and palliative responses. RESULTS: At the time of second-line chemotherapy, the median age of the patients was 69 years (range: 46 to 83). The median interval between the end of first-line chemotherapy and the start of second-line chemotherapy was 3 months (range: 1 to 15). The protocols administered comprised docetaxel alone (12 patients) or in combination with cisplatin (4 patients), mitoxantrone in 13 patients, or other cytotoxic molecules such as vinblastine, doxorubicin or etoposide in combination with a platinum salt (14 patients). The median number of cycles delivered was 4 (range: 1 to 10). No objective response was observed. Six (14%) patients obtained a laboratory response. A palliative response was observed in 16 (37%) patients, 7 of whom were treated with a docetaxel-based protocol, 6 were treated with mitoxantrone and 3 were treated by other protocols. The median duration of palliative response was 3 months (range: 1 to 6). The median survival was 8 months (range: 1 to 24), with no significant difference between the various protocols. CONCLUSION: In 2006, the objective of second-line chemotherapy in patients with hormone-resistant prostate cancer appears to be purely palliative. No reference protocol has been defined among currently available cytotoxic molecules. The indication must therefore take into account the benefit/risk balance to avoid compromising the patients quality of life. Therapeutic trials are essential to develop effective new molecules.

Subcutaneous interleukin-2 and interferon-alpha in metastatic renal cell carcinoma: results of a French regional experience in Languedoc.

OBJECTIVES: To assess the efficacy and toxicity of an immunotherapy regimen combining subcutaneous (SC) interleukin-2 (IL-2) and interferon-alpha (IFN) in patients with metastatic renal cell carcinoma (MRCC). METHODS: The present study included 86 patients with MRCC. Data on treatment toxicity and efficacy (responses rates and overall survival) were collected on a hospital database. Treatment consisted of 6-week cycles repeated every 2 months for a maximum of 3 cycles. Each cycle included SC IL-2 20 x 10 MIU/m2 3 times/wk on weeks 1 and 4; 5 x 10 MIU/m2 3 times/wk on weeks 2, 3, 5, and 6, in combination with IFN 6 x 10 MIU/m2 once weekly on weeks 1 and 4; and 3 times/wk on weeks 2, 3, 5, and 6. RESULTS: Seventy (82%) and 71 (83%) patients received more than 80% of the planned doses of IL-2 and IFN during the first cycle, respectively. Ten patients had to stop therapy before the end of the first cycle because of excessive toxicity (7 patients) or rapidly progressive disease (3 patients). Only 17 (28%) proceeded to the second cycle. Main toxicities included fever and asthenia in 86 (100%) patients, nausea/emesis in 83 (96%) patients, skin disorders in 69 (80%) patients, hypotension in 56 (65%) patients, and diarrhea in 50 (58%) patients. Sixty-seven (78%) patients developed at least one episode of grade 3 toxicity. Objective responses were observed in 13 patients, including 4 complete and 9 partial responses (15%; 95% confidence interval, 9.5-20.5%). After a median follow-up of 45 months, the median time to progression was 4 months (range, 1-41) and the median survival was 14 months (range, 1-89). CONCLUSIONS: Only a small subset of patients with MRCC is likely to benefit from treatment with IL-2 and IFN. As toxicity is significant, the refinement of predictive variables for sensitivity to immunotherapy is mandatory.

Gemcitabine and oxaliplatin in advanced transitional cell carcinoma of the urothelium: a pilot study.

BACKGROUND: Despite the fact that new drugs have emerged from clinical research in urothelial cancer during the last decade, the prognosis of patients with advanced disease remains poor with a median survival of 12 to 14 months. We designed a feasibility study of gemcitabine and oxaliplatin (GO) in patients with advanced urothelial cancer. PATIENTS AND METHODS: Twenty patients received bimonthly cycles of gemcitabine 1500 mg/m2 and oxaliplatin 85 mg/m2. The cycles were given at 2-week intervals without G-CSF support. Thirteen patients were treated with the GO combination as first-line chemotherapy because of a poor performance status or a creatinine clearance < 1 ml/s. RESULTS: The median number of cycles of GO was 5 (1-7). The median number of days between cycles was 14 throughout the treatment. Seven (8%) out of 87 cycles had to be delayed because of neutropenia or asthenia. A 25% dose reduction in the doses of cytotoxic drugs was necessary in 2 patients. Chemotherapy was stopped before the sixth cycle because of an early death related to a myocardial infarction in 1 patient, a grade 3 neuropathy in 1 patient and a progressive disease in 9 patients. CONCLUSION: Using these doses and schedules, the GO regimen appears a safe therapy for patients with advanced urothelial cancer. Phase II studies are required to assess the possible role of this combination in advanced urothelial cancer.