Our experience with 23 consecutive patients on gemcitabine/carboplatin chemotherapy for treatment of metastasized transitional cell carcinoma of the urothelium

Abstract

Aim : To evaluate the activity and toxicity of gemcitabine plus carboplatin in patients with metastatic transitional cell carcinoma (TCC) of the urothelium. Methods : Twenty-three consecutive patients (from February 1999 to January 2002) with metastatic TCC and no prior chemotherapy were referred to our institution. Each patient was treated with gemcitabine (1000 mg/m 2 ) on Days 1 and 8 and carboplatin (area under curve, 4.5) on Day 1. Cycles were repeated every 21 days until tumor progression or severe toxicity was seen, or for a maximum of six cycles. Median age of the patients was 68 years (range 47-82). The median Eastern Cooperative Oncology Group (ECOG) performance score was one and the median creatinine clearance rate was 56 mL/min (range 31-94). Results : The overall response rate was 60.8%, with five of the 23 patients achieving a complete response, and nine showing a partial response. Median time to tumor progression (TTP) was 7.8 months, with a median survival of 15.4 months and a 1-year survival probability of 56%. Most of the complications from toxicity were hematological. Conclusions : Gemcitabine plus carboplatin is active in the treatment of metastatic urothelial cancer in those patients new to chemotherapy and has an acceptable safety profile. The potential clinical benefit of this novel combination in the treatment of transitional cell carcinoma warrants further testing in Phase III studies.

Gemcitabine and carboplatin in the treatment of transitional cell carcinoma of the urothelium: a single centre experience and review of the literature

“…Overall, the treatment was well tolerated. The grades 3 and 4 haematological toxicity rates were similar to those seen in previously published studies (Bellmunt et al 2001;Shannon et al 2001;Nogue-Aliguer et al 2003;Hoschke et al 2004;Linardou et al 2004;Bamias et al 2006). Only one patient suffered a grade 3 non-haematological toxicity and there were no treatment-related deaths.…”

“…One logical approach was to substitute carboplatin for cisplatin because of carboplatin's more favourable toxicity profile. Several non-randomized phase 2 studies have shown GCarbo to have activity in the first-line treatment of metastatic TCC in patients deemed unfit for cisplatin, with a reported median survival of 7.2-15.4 months (Table 3) (Shannon et al 2001;Nogue-Aliguer et al 2003;Hoschke et al 2004;Linardou et al 2004).…”

“…The dose-limiting toxicity of carboplatin is myelosupression, but at standard doses it is less emetogenic and does not cause nephrotoxicity, ototoxicity or neurotoxicity. Several phase 2 studies have shown the combination of gemcitabine and carboplatin (GCarbo) to have activity and an acceptable safety profile in urothelial TCC (Bellmunt et al 2001;Shannon et al 2001;Nogue-Aliguer et al 2003;Hoschke et al 2004;Linardou et al 2004;Bamias et al 2006). From July 2003 to June 2007, 15 consecutive patients with metastatic TCC of the urothelium were treated with GCarbo, and we present the outcomes.…”

Combined Gemcitabine and Carboplatin Therapy for Carcinomas in Dogs

“…While the ideal time between GEM administration and platinum drug exposure (“wait period”) can vary among cell types, a minimum of 4 hours is recommended between administration of these drugs for superior cytotoxic effects to occur 22,26,27 . In people, phase II/III trials of GEM‐platinum combinations have yielded response rates in the range of 30–75% for various tumor types including carcinoma of the cervix, breast, nasopharyngeal region, and bladder 28–33 . While GEM‐platinum combinations appear to be well tolerated, hematologic, renal, and gastrointestinal (GI) toxicoses are commonly reported.…”

A phase II trial of gemcitabine plus carboplatin in advanced transitional cell carcinoma of the urothelium

“…56% of patients obtained an objective response, with a median survival time of 10 months. Three small trials used the same schedule and doses as those of the Carles trial and demonstrated response rates in the range of 44–61% with the GC combination [16-18]. In addition four larger phase II studies, Nogue-Aliguer et al reported their results in 41 patients, of whom some, but not all, had unfavorable characteristics (creatinine clearance less than 60 ml/min in 54% of patients and Karnofsky performance status of 70 or less in 37%).…”