Gemcitabine plus carboplatin versus gemcitabine plus oxaliplatin in cisplatin-unfit patients with advanced urothelial carcinoma: a randomised phase II study (COACH, KCSG GU10-16).

Purpose: Gemcitabine-oxaliplatin (GEMOX) demonstrated mild toxicity and promising effectiveness in patients with advanced urothelial cell cancer (UCC). We investigated the activity and safety of first-line GEMOX compared with gemcitabine-carboplatin (GCb) in cisplatin-ineligible patients with advanced UCC.

Methods: Treatment-naive, cisplatin-ineligible patients with advanced UCC were randomly assigned to GEMOX (gemcitabine 1000 mg/m, oxaliplatin 100 mg/m on day 1 [D1] every 2 weeks) or GCb (1000 mg/m of gemcitabine on D1 and D8 and carboplatin area under the curve of 4.5 mg/mL/min on D1 every 3 weeks). We evaluated the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).

Results: Between January 2011 and March 2017, 80 patients were enrolled; 39 and 40 patients were allocated to GCb and GEMOX arms, respectively. The ORR was 48.7% in the GCb arm and 55.0% in the GEMOX arm. The median follow-up duration was 37.8 months; the median PFS and OS in the GCb and GEMOX arms were 5.5 months (95% confidence interval [CI], 4.8-6.2) vs. 4.4 months (95% CI, 2.7-6.1) and 9.1 months (95% CI, 5.2-13.0) vs. 11.0 months (95% CI, 6.9-15.0), respectively. ≥Leucopenia, neutropenia and fatigue of ≥ grade III were significantly more common in the GCb arm (26% vs. 3%, P = 0.003; 33% vs. 10%, P = 0.014; 15% vs. 3%, P = 0.012), whereas any-grade neuropathy was more common in the GEMOX arm (8% vs. 60%).

Conclusions: GEMOX showed similar efficacy with GCb and a favourable haematologic toxicity profile. GEMOX may be an additional chemotherapy option for patients with UCC ineligible for cisplatin-containing chemotherapy (NCT01487915).