title: Treosulfan and gemcitabine in metastatic uveal melanoma patients: results of a multicenter feasibility study.
abstract: No effective treatment currently exists for metastatic uveal melanoma. However, recent results obtained by an ATP-based tumor chemosensitivity assay have shown consistent activity of treosulfan+gemcitabine in up to 80% of tumor specimens tested. In this study we describe the first clinical results observed with this drug combination at different European centers in patients with metastatic uveal melanoma. Clinical case series of patients with metastatic uveal melanoma were treated with treosulfan+gemcitabine at seven different centers. Fourteen patients, 13 previously untreated and one pretreated with chemoimmunotherapy, were included in the study. Patients received treosulfan+gemcitabine in four different dose regimens. The response rates, progression-free and overall survival, and toxicity were evaluated. The analysis of 14 patients revealed one complete response, three partial responses and a stable disease in eight cases. The objective response rate was 28.6%, the median overall survival was 61 weeks [95% confidence interval (CI) 54-133 weeks], the progression-free survival was 28.5 weeks (95% CI 13-62 weeks) and the 1-year survival rate was 80%. The drugs were well tolerated. The most common side-effects were leuko- and thrombocytopenia. These preliminary results suggest potential therapeutic benefit of treosulfan+gemcitabine treatment in metastatic uveal melanoma and warrant further controlled studies.
authors.affiliation: Saarland University Hospital, Department of Dermatology, Homburg/Saar, Germany. hacpfo@uniklinik-saarland.de
authors.forename: Claudia
authors.initials: C
authors.lastname: Pföhler
authors.forename: Ian A
authors.initials: IA
authors.lastname: Cree
authors.forename: Selma
authors.initials: S
authors.lastname: Ugurel
authors.forename: Christoph
authors.initials: C
authors.lastname: Kuwert
authors.forename: Nikolas
authors.initials: N
authors.lastname: Haass
authors.forename: Karsten
authors.initials: K
authors.lastname: Neuber
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hengge
authors.forename: Pippa G
authors.initials: PG
authors.lastname: Corrie
authors.forename: Markus
authors.initials: M
authors.lastname: Zutt
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Tilgen
authors.forename: Uwe
authors.initials: U
authors.lastname: Reinhold
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018450:Disease Progression; D005240:Feasibility Studies; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D010865:Pilot Projects; D016019:Survival Analysis; D014604:Uveal Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D003841:Deoxycytidine; C018404:treosulfan; D002066:Busulfan; D000093542:Gemcitabine