Phase II trial of pemetrexed plus gemcitabine in patients with locally advanced and metastatic nonclear cell renal cell carcinoma.

Objective: To determine the clinical activity and safety of the combination of pemetrexed and gemcitabine in advanced nonclear cell renal cell carcinoma (nccRCC).

Methods: In this phase II study, patients received pemetrexed 500 mg/m intravenous infusion over 10 minutes on day 1 followed immediately by gemcitabine 1500 mg/m intravenously over 30 minutes on day 1, with cycles repeated every 14 days. Planned enrollment was 40 patients. The primary endpoints were objective response rate and progression-free survival (PFS). The secondary endpoints were safety and overall survival.

Results: Between December 2005 and December 2008, 16 patients with locally advanced or metastatic nccRCC were enrolled. The trial was stopped early due to low efficacy and excessive toxicity. The objective response rate was 0% [95% confidence interval (CI), 0%-18%]. The median number of cycles administered was 4 (range, 1 to 12). Median PFS was 3.2 months (95% CI, 1.9-6+), and the 16-week PFS rate was 46.7% (95% CI, 19.8%-100%). Median overall survival was 23.2 months (95% CI, 12.9-38.1). The most common grade 3 or 4 adverse events were neutropenia (53%), leukopenia (53%), anemia (13%), fatigue (40%), and renal insufficiency (13%).

Conclusions: In this phase II trial in nccRCC, the combination of pemetrexed and gemcitabine was toxic and ineffective. Further development of this regimen in nccRCC is not warranted.