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

Abstract

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 72 and cisplatin 75 mg m 72 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.

Larotaxel with Cisplatin in the First-Line Treatment of Locally Advanced/Metastatic Urothelial Tract or Bladder Cancer: A Randomized, Active-Controlled, Phase III Trial (CILAB)

“…Phase II trials of patients with advanced bladder cancer treated with the combination of a taxane and cisplatin have reported response rates (RRs) of 52-70%, times to progression of 5-7 months, and OS of 8-14 months, with a safety profile consistent with that reported in patients with other solid tumors [10,11,12,13,14]. However, a phase III trial conducted by the Hellenic Cooperative Oncology Group found that docetaxel in combination with cisplatin was less effective than M-VAC (both regimens given with prophylactic granulocyte colony-stimulating factor) in terms of RR, progression-free survival (PFS), and OS [15].…”

Adjuvant chemotherapy for transitional cell carcinoma of the bladder: Paradigms for the design of clinical trials

“…Several phase II trials have shown that newer drugs, such as paclitaxel and docetaxel, have potential as single agents or in combination in the treatment of metastatic urethelial cancer [30][31][32][33]. Carboplatin has also been tested in patients with renal dysfunction [31,32].…”

The Role of Taxanes in the Management of Bladder Cancer

“…In a multicenter phase II trial, 38 previously untreated patients with advanced/metastatic TCC received docetaxel 75 mg/m 2 and cisplatin 75 mg/m 2 every 21 days [10]. There were seven (19%) complete responses and 15 (39%) partial responses for an overall response rate of 58% (95% CI, 41%-74%).…”