Gemcitabine and carboplatin in advanced transitional cell carcinoma of the urinary tract

Abstract

BACKGROUND Cisplatin‐based combinations are considered to be the standard treatment for advanced transitional cell carcinoma (TCC) of the urothelium. Many of the patients are elderly with concomitant diseases or impaired renal function. We studied the tolerance and activity of the gemcitabine/carboplatin combination as a therapeutic alternative. METHODS Patients with locally advanced or metastatic TCC of the urothelium were treated with gemcitabine 1000 mg/m2 on Days 1 and 8 and carboplatin area under the concentration‐time curve 5 on Day 1 every 21 days. Patients with creatinine clearance of 30 mL/min or above and Karnofsky performance status (KPS) scores 60 or above were enrolled. RESULTS A total of 227 cycles were administered to 41 patients, with an average of 5.5 cycles per patient (range, 1–8 cycles). Creatinine clearance was below 60 mL/min in 54% of patients, KPS was 70 or below in 37% of patients, and 37% of patients were 70 years old or older. Hematologic toxicity was mainly Grade 3/4 neutropenia in 63%, Grade 3/4 thrombocytopenia in 32%, and Grade 3/4 anemia in 54% of patients. There were only three episodes of febrile neutropenia and one death from neutropenic sepsis. Nonhematologic toxicity was mild, with asthenia as the most frequently reported event. We obtained 6 complete and 17 partial responses, for an overall response rate of 56.1% (95% confidence interval [CI], 40.6–71.6%). Progression‐free survival was 7.2 months (95% CI, 5.7–8.5) and median survival was 10.1 months (95% CI, 8.8–12.2). CONCLUSIONS The combination of gemcitabine plus carboplatin achieves a similar result to doublets using cisplatin. It has an acceptable toxicity profile and enables patients with impaired renal function and/or poor performance status and elderly patients to be treated. Cancer 2003;97:2180–6. © 2003 American Cancer Society. DOI 10.1002/cncr.10990

First- and Second-Line Therapy for Metastatic Urothelial Carcinoma of the Bladder

“…The study was closed early, and no conclusions could be made 26 . Similarly, a carboplatin regimen was investigated alongside gemcitabine in phase ii trials that did not exclude patients fit to receive cisplatin, resulting in ors of 56% and 59% and a median os of only 10 months [27][28][29] . In a phase ii randomized trial of gc versus gemcitabine with carboplatin, better response rates were observed with gc (66% vs. 35%) without significant differences in toxicity profile 30 .…”

Gemcitabine and Carboplatin (Renally Dosed) Regimen for Bladder Cancer

“…22, 23 The studies reviewed reported nausea in 14%, 6 nausea and vomiting in 10% to 47%, 2,8,9 grade 3 to 4 nausea and vomiting in 7% to 65%, 2,5 vomiting in 32%, 3 and grade 3 or 4 vomiting in 7% of patients. 3 Appropriate acute emesis prophylaxis includes a serotonin antagonist and a corticosteroid plus or minus a neurokinin antagonist in selected patients. 22,23 One of the following regimens is suggested: The antiemetic therapy should continue for at least 2 days after day 1.…”

“…The GCarbo regimen ( Table 1) has been studied in metastatic bladder cancer [1][2][3][4][5][6] and is recommended as an alternative regimen to first-line chemotherapy in metastatic disease. 7 The GCarbo regimen has also been studied as perioperative chemotherapy, specifically neoadjuvant chemotherapy, in locally advanced bladder cancer prior to cystectomy.…”

“…In the trials reviewed, neutropenia was reported in 50% to 100% [1][2][3]6,8,9 of patients and grade 3 to 4 neutropenia in 7% to 70% [1][2][3][4][5][6]8,9 of patients. Febrile neutropenia was reported in 3% to 25% of patients.…”

Advanced bladder cancer: Status of first‐line chemotherapy and the search for active agents in the second‐line setting

“…Three small phase 2 trials comparing cisplatin with carboplatin reported similar overall RRs (ORRs), with less toxicity noted in the carboplatin arms. [19][20][21] A European Organization for Research and Treatment of Cancer (EORTC) phase 3 trial of M-VAC versus carboplatin and paclitaxel closed early because of poor accrual. 22 Trials of carboplatin-based regimens in patients with normal renal function have demonstrated encouraging ORRs in the range of 30% to 40%, but the CR rates are lower and they are paralleled by shorter median survivals of 8 months to 10 months.…”