gms | German Medical Science

Purpose: Preclinical studies suggested a synergy of treosulfan and gemcitabine in chemotherapy resistent tumors. This trial investigated the clinical efficacy of gemcitabine plus treosulfan (GeT) in metastatic uveal melanoma. Experimental Design: Patients received 1000mg/m2 of gemcitabine. Treosulfan was added in a dose of 2500 or 3000mg/m2 in cohort 1 or in a dose of 3500 or 4000 mg/m2 in cohort 2. Chemotherapy was administered on days 1 and 8, cycles were repeated on day 29. In the absence of disease progression a maximum of 6 cycles were administered.

Results: Thirty-three patients with metastatic uveal melanoma received therapy. Fourteen were accrued in cohort 1 and nineteen in cohort 2. In cohort 1 with a treosulfan dose < 3000mg/m2 no objective response was observed, four patients had stable disease and ten progressed. Of patients treated with > 3500mg/m2 in cohort 2 one had a partial remission, ten disease stabilisation and eight progressed. An increased survival in the second cohort with higher treosulfan doses was observed, with a median survival of 6.0 vs. 9.0 months (p=0.03) in cohort 1 and 2, respectively and a one year survival of 7.1% vs. 47.3%. A strong pretreatment prognostic factor for survival was the serum LDH level.

Conclusions: The recommended dose for treosulfan is 3500mg/m2. In a randomized phase II study we are currently comparing the GeT regimen versus a treosulfan monotherapy in metastatic uveal melanoma.