A phase II study of gemcitabine and docetaxel therapy in patients with advanced urothelial carcinoma

Abstract

BACKGROUND The objectives of the current study were to evaluate the safety and efficacy of gemcitabine plus docetaxel in patients with unresectable (Stage T4 or ≥ N1) metastatic or locally advanced transitional cell carcinoma (TCC) of the urothelial tract. METHODS A total of 27 patients were enrolled in the current multisite study, which was performed within the University of California‐Los Angeles Community Oncology Research Network. The first 10 patients in the study received 800 mg/m2 of gemcitabine intravenously on Days 1, 8, and 15 of a 28‐day treatment cycle. In addition, on Day 1, the first 10 patients received 80 mg/m2 of docetaxel intravenously after completion of the gemcitabine infusion. Because of dose‐limiting toxicity (neutropenia), the initial dose of docetaxel was reduced to 60 mg/m2 for the remaining patients who entered the study (n = 17 patients). RESULTS Neutropenia was the most common adverse event that occurred in patients at the Grade 3 level (in 10 of 27 patients; 37.0%) and the Grade 4 level (in 6 of 27 patients; 22.2%). There were no other adverse events at the Grade 4 toxicity level. Twenty‐five of 27 patients (92.6%) completed more than 1 cycle of combination therapy and were evaluated for antitumor responses. The frequency of objective clinical responses was 33.3% (9 of 27 patients). Complete responses to therapy were observed in 2 of 27 patients (7.4%), and partial responses were observed in 7 of 27 patients (25.9%). The median duration of response was 20 weeks (range, 12+ weeks to 152 weeks). The median survival duration was 52 weeks (range, 12 weeks to 160+ weeks). Four of 27 patients (14.8%) remained alive at the time of the current data analysis. CONCLUSIONS The results of the current study suggested that combination therapy with gemcitabine and docetaxel was an effective treatment for patients with unresectable (Stage T4 or ≥ N1) metastatic or locally advanced TCC of the urothelial tract. Gemcitabine plus docetaxel appeared to be tolerated well, and treatment‐related toxicities were limited to hematologic toxicities. Because cisplatin‐containing regimens are contraindicated for patients with impaired renal function, the gemcitabine plus docetaxel combination may prove to be an effective and well tolerated treatment option for these patients. Cancer 2003. © 2003 American Cancer Society.

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

“…Furthermore, a regimen consisting of docetaxel and gemcitabine showed promising response rates of 30%-50% and median os times of 13-15 months in phase ii trials [33][34][35] . Finally, gemcitabine was also combined with pemetrexed in phase ii trials, resulting in modest response rates of about 25%, but with increased toxicity 36 .…”

Gynecologic oncology group trials of chemotherapy for metastatic and recurrent cervical cancer

“…In three phase II studies involving patients with carcinoma of unknown primary site [68], advanced urothelial carcinoma [69], and advanced pancreatic cancer [70], the doublet gemcitabine and docetaxel produced objective response rates ranging from 27% to 40%. In all three studies, the regimen was well tolerated and toxicity was manageable.…”

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“…For patients with impaired renal function, carboplatin-based regimens can be used as the first-line for metastatic TCC, however, its efficacy remains to be evaluated with larger phase III trials (9). Non-platinum regimens, particularly those combining gemcitabine with either paclitaxel or docetaxel have also shown promising results in several phase II studies (10,11).…”