title: A two-cohort phase II clinical trial of gemcitabine plus treosulfan in patients with metastatic uveal melanoma.
abstract: 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.
authors.affiliation: Department of Internal Medicine III (Haematology, Oncology and Transfusion Medicine), Charité - Campus Benjamin Franklin, Berlin, Germany. alexander.schmittel@charite.de
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmittel
authors.forename: Ronny
authors.initials: R
authors.lastname: Schuster
authors.forename: Nikolaos E
authors.initials: NE
authors.lastname: Bechrakis
authors.forename: Jan M
authors.initials: JM
authors.lastname: Siehl
authors.forename: Michael H
authors.initials: MH
authors.lastname: Foerster
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keilholz
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016019:Survival Analysis; D016896:Treatment Outcome; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; C018404:treosulfan; D002066:Busulfan; D000093542:Gemcitabine