title: A phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma.
abstract: Temozolomide is an alkylating agent with activity in the treatment of melanoma metastatic to the brain. Lomustine is a nitrosurea that crosses the blood brain barrier and there is evidence to suggest that temozolomide may reverse resistance to lomustine. A multicentre phase I/II study was conducted to assess the maximum-tolerated dose (MTD), safety and efficacy of the combination of temozolomide and lomustine in melanoma metastatic to the brain. Increasing doses of temozolomide and lomustine were administered in phase I of the study to determine the MTD. Patients were treated at the MTD in phase II of the study to six cycles, disease progression or unacceptable toxicity. Twenty-six patients were enrolled in the study. In phase I of the study, the MTD was defined as temozolomide 150 mg m(-2) days 1-5 every 28 days and lomustine 60 mg m(-2) on day 5 every 56 days. Dose-limiting neutropaenia and thrombocytopaenia were observed at higher doses. Twenty patients were treated at this dose in phase II of the study. No responses to therapy were observed. Median survival from starting chemotherapy was 2 months. The combination of temozolomide and lomustine in patients with brain metastases from melanoma does not demonstrate activity. The further evaluation of this combination therefore is not warranted.
authors.affiliation: Department of Medicine, Royal Marsden Hospital, London SW3 6JJ, UK.
authors.forename: J M G
authors.initials: JM
authors.lastname: Larkin
authors.forename: S A
authors.initials: SA
authors.lastname: Hughes
authors.forename: D A
authors.initials: DA
authors.lastname: Beirne
authors.forename: P M
authors.initials: PM
authors.lastname: Patel
authors.forename: I M
authors.initials: IM
authors.lastname: Gibbens
authors.forename: S C
authors.initials: SC
authors.lastname: Bate
authors.forename: K
authors.initials: K
authors.lastname: Thomas
authors.forename: T G
authors.initials: TG
authors.lastname: Eisen
authors.forename: M E
authors.initials: ME
authors.lastname: Gore
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D000077204:Temozolomide; D013921:Thrombocytopenia / Q000139:chemically induced; D017211:Treatment Failure
chemical_list: D008130:Lomustine; D003606:Dacarbazine; D000077204:Temozolomide