A two-cohort phase II clinical trial of gemcitabine plus treosulfan in patients with metastatic uveal melanoma.

In-vitro synergy of treosulfan and gemcitabine has been observed in chemotherapy-resistant tumours. This trial investigated the efficacy of gemcitabine plus treosulfan in metastatic uveal melanoma. Patients received 1000 mg/m of gemcitabine and treosulfan at a dose of 2500 or 3000 mg/m2 in cohort 1 and 3500 or 4000 mg/m2 in cohort 2. Chemotherapy was administered on days 1 and 8 every 4 weeks. Thirty-three patients were treated, 14 in cohort 1 and 19 in cohort 2. In cohort 1 with a treosulfan dose of <or=3000 mg/m2, no objective response was observed, four patients had stable disease and ten progressed. Of the patients treated with >or=3500 mg/m2 in cohort 2, one had partial remission (5%), 10 showed disease stabilization and eight progressed. An increased survival was observed in the second cohort with higher treosulfan doses, with median survival times of 6.0 versus 9.0 months (P=0.03) in cohort 1 and 2, respectively, and a 1-year survival of 7.1% versus 47.3%, respectively. Based on the observation of prolonged disease stabilization, we recommend further investigation of the gemcitabine/treosulfan combination with a dose of 3500 mg/m2 of treosulfan in metastatic uveal melanoma.