title: A clinical phase I trial of gemcitabine and treosulfan in uveal melanoma and other solid tumours.
abstract: This trial was performed to define the maximum tolerated dose (MTD) of treosulfan administered in combination with a fixed dose of gemcitabine in uveal melanoma patients. Preclinical studies suggested synergistic activity against uveal melanoma. Gemcitabine (1 g/m2) and treosulfan (2.5-4 g/m2) were administered on days 1 and 8, and cycles were repeated on day 29 for a maximum of six cycles. For treosulfan, dose escalation cohorts of 2-4 patients were enrolled. An additional 25 patients were entered at treosulfan dose levels II (3 g/m2) and III (3.5 g/m2). Thirty three patients with uveal melanoma and six patients with other histologies were accrued. Side-effects were predominantly haematological. The MTD was 3.5 g/m2 of treosulfan together with 1 g/m2 of gemcitabine. In the uveal melanoma patients, one partial response (PR) and 15 stablisations of disease (SD) were recorded and whether this translates into a survival gain should be explored further.
authors.affiliation: Department of Medicine III (Hematology, Oncology and Transfusion Medicine), Free University Berlin, Charité--Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Germany. ulrich.keilholz@charite.de
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keilholz
authors.forename: Ronny
authors.initials: R
authors.lastname: Schuster
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmittel
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Bechrakis
authors.forename: Jan
authors.initials: J
authors.lastname: Siehl
authors.forename: Michael H
authors.initials: MH
authors.lastname: Foerster
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
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*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D016896:Treatment Outcome; D014604:Uveal Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; C018404:treosulfan; D002066:Busulfan; D000093542:Gemcitabine