A Randomized Phase 2 Trial of Gemcitabine/Cisplatin With or Without Cetuximab in Patients With Advanced Urothelial Carcinoma CANCER Hussain, M., Daignault, S., Agarwal, N., Grivas, P. D., Siefker-Radtke, A. O., Puzanov, I., MacVicar, G. R., Levine, E. G., Srinivas, S., Twardowski, P., Eisenberger, M. A., Quinn, D. I., Vaishampayan, U. N., Yu, E. Y., Dawsey, S., Day, K. C., Day, M. L., Al-Hawary, M., Smith, D. C. 2014; 120 (17): 2684-2693


Epidermal growth factor receptor overexpression is associated with poor outcomes in urothelial carcinoma (UC). Cetuximab (CTX) exhibited an antitumor effect in in vivo UC models. The efficacy of gemcitabine/cisplatin (GC) with or without CTX in patients with advanced UC was evaluated.Patients with advanced UC, measurable disease, and adequate organ function were randomized 1:2 to cisplatin (70 mg/m(2) ) on day 1 plus gemcitabine (1000 mg/m(2) ) on days 1, 8, and 15 (arm A) or GC plus CTX (500 mg/m(2) ) on days 1 and 15 (arm B). The primary endpoint was the overall response rate. The secondary endpoints were the response duration, safety, progression-free survival, overall survival, determination of whether or not CTX sensitized nonresponders to GC, and exploratory biomarker analysis. The accrual targets were 27 and 54 patients for the 2 arms, respectively. The overall response rate was reported by arm with binomial confidence intervals (CIs). Kaplan-Meier methods were used for time-to-event endpoints.Eighty-eight eligible patients were randomized; 87 were toxicity-evaluable, and 85 were response-evaluable. The overall response rates were 57.1% for arm A (95% CI?=?37%-76%) and 61.4% for arm B (95% CI?=?48%-74%). The median progression-free survival times were 8.5 months for arm A (95% CI?=?5.7-10.4 months) and 7.6 months for arm B (95% CI?=?6.1-8.7 months). The median overall survival times were 17.4 months for arm A (95% CI?=?12.8 months to unreached) and 14.3 months for arm B (95% CI?=?11.6-22.2 months). The most common grade 3/grade 4 adverse events in both arms were myelosuppression and nausea. Thromboembolism, acneiform rash, fatigue, pain, hypersensitivity reactions, elevated transaminases, hyponatremia, and hypomagnesemia were more common in arm B; 3 grade 5 adverse events occurred in arm B. The presence of primary disease significantly correlated with thromboembolism. An increased soluble E-cadherin level after cycle 2 correlated with a higher risk of death.GC plus CTX was feasible but was associated with more adverse events and no improvements in outcomes.

View details for DOI 10.1002/cncr.28767

View details for Web of Science ID 000340559000009

View details for PubMedID 24802654

View details for PubMedCentralID PMC4142676