title: A prospective single arm phase II study of dacarbazine and treosulfan as first-line therapy in metastatic uveal melanoma.
abstract: Uveal melanoma is relatively uncommon accounting for fewer than 5% of all melanoma cases. Localized tumours are curable by local therapy but a significant percentage of patients go on to have a relapse with metastatic disease. Uncertainty remains concerning the level of activity of dacarbazine in uveal melanoma as opposed to that in the cutaneous form. Recently, a possible role for treosulfan in uveal disease has been reported. A phase II study was therefore undertaken to assess the objective response rate of the combination of dacarbazine and treosulfan in previously untreated patients with metastatic uveal melanoma. All patients received dacarbazine 850 mg/m and treosulfan 8 g/m(2) every 21 days up to a maximum of six cycles. Fifteen patients enrolled in the study. As expected, the major toxicities were haematological (particularly thrombocytopaenia) but the treatment was generally well tolerated. No responses were seen; however, disease stabilization was achieved in two patients. Median progression free survival from the start of chemotherapy was 12 weeks and median overall survival was 30 weeks. This study, using the combination of dacarbazine and treosulfan, while well tolerated, did not confirm earlier reports suggesting treosulfan is active in uveal melanoma.
authors.affiliation: Clatterbridge Centre for Oncology, Bebington, Wirral, Merseyside, UK.
authors.forename: Penny A
authors.initials: PA
authors.lastname: O'Neill
authors.forename: Mohammad
authors.initials: M
authors.lastname: Butt
authors.forename: Chinnamani V
authors.initials: CV
authors.lastname: Eswar
authors.forename: Pat
authors.initials: P
authors.lastname: Gillis
authors.forename: Ernest
authors.initials: E
authors.lastname: Marshall
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011446:Prospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced; D014604:Uveal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology
chemical_list: D003606:Dacarbazine; C018404:treosulfan; D002066:Busulfan