The combination of gemcitabine and carboplatin as first-line treatment in patients with advanced urothelial carcinoma : A phase II study of the hellenic cooperative oncology group

• Published in: Cancer Vol. 106; no. 2; pp. 297 - 303
• Main Authors: BAMIAS, Aristotle, MOULOPOULOS, Lia A, KALOFONOS, Haralambos P, DIMOPOULOS, Meletios A, KOUTRAS, Aggelos, ARAVANTINOS, Gerassimos, FOUNTZILAS, George, PECTASIDES, Dimitris, KASTRITIS, Efstathios, GIKA, Dimitros, SKARLOS, Dimosthenis, LINARDOU, Helena
• Format: Journal Article
• Language: English
• Published: New York, NY Wiley-Liss 15.01.2006
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carboplatin - adverse effects; Carboplatin - therapeutic use; Carcinoma - drug therapy; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Female; Humans; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Treatment Outcome; Tumors; Tumors of the urinary system; Urinary Bladder Neoplasms - drug therapy; Urinary tract. Prostate gland; Urothelium - pathology; Antineoplastic agent; Human; Urinary system disease; Gemcitabine; activity; Urinary tract disease; Transitional cell carcinoma; Malignant tumor; Bladder carcinoma; Bladder cancer; Biological activity; First line treatment; Cancerology; Antimetabolic; Phase II trial; Carboplatin; Pyrimidine derivatives; Advanced stage; Bladder disease; first-line treatment; Fluorine Organic compounds; Pyrimidine nucleoside; Platinum II Complexes
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.21604

The toxicity of platinum-based combinations represents a common problem for patients with advanced urothelial carcinoma. The authors previously reported encouraging efficacy for the combination of carboplatin and gemcitabine in patients considered to be unfit for cisplatin-based treatment. The objective of the current multicenter Phase II study was to evaluate the safety and efficacy of the combination of gemcitabine and carboplatin as first-line treatment in unselected patients with advanced urothelial carcinoma. Patients with previously untreated, bidimensionally measurable, inoperable or metastatic urothelial carcinoma were treated with carboplatin, area under the concentration curve of 5 (Day 1) and gemcitabine at a dose of 1000 mg/m(2) (Days 1 and 8), every 21 days for a total of 6 cycles. Sixty patients (49 men and 11 women, with a median age of 69 yrs) were enrolled in the current study. Intent-to-treat analysis demonstrated an objective response rate (ORR) of 38.4% (95% confidence interval [95% CI], 26-51.8%) (11.7% complete responses and 26.7% partial responses). The median time to disease progression was 7.6 months (95% CI, 4.5-10.7 mos) and the median overall survival was 16.3 months (95% CI, 12-20.6 mos). The median survival was comparable to that reported for the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) according to the Memorial Sloan-Kettering Cancer Center prognostic model for patients with similar baseline prognostic features. Grade 3 or 4 toxicity (according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) included anemia (18%), thrombocytopenia (23%), and neutropenia (52%), with 7 episodes of febrile neutropenia (11%) reported. Nonhematologic toxicity was rare. One toxic death occurred during the study. The combination of gemcitabine and carboplatin appears to have considerable activity as the first-line treatment of unselected patients with advanced urothelial carcinoma with manageable toxicity, and deserves further evaluation in this setting.