title: Vinorelbine combined with a protracted course of temozolomide for recurrent brain metastases: a phase I trial.
abstract: Temozolomide (TMZ) has shown modest efficacy in the treatment of recurrent brain metastasis (BM). We designed a new regimen utilizing dose-intensified, protracted course of TMZ in combination with vinorelbine, a lipophilic large-spectrum agent, in an attempt to improve the efficacy of TMZ. This phase I study was conducted to establish the maximum tolerated dose (MTD) of vinorelbine for this combination. Patients with recurrent or progressive BM were eligible. Chemotherapy consisted of 28-day cycles with TMZ (150 mg/m2, days 1-7 and 15-21) and vinorelbine (days one and eight at escalating doses). The starting dose was 15 mg/m2, with increments of 5 mg/m2 for each cohort of 3-6 patients, until MTD was reached (30 mg/m2). A total of 21 patients were enrolled; the median age was 59 (41-77). The primary tumor was lung cancer in 13 patients (NSCLC in 10, SCLC in 3), breast in 6, renal in 1 and endometrial in 1. Vinorelbine dose was 15 mg/m2 in seven patients, 20 mg/m2 in five, 25 mg/m2 in four and 30 mg/m2 in six. Grades 3 and 4 neutropenia developed in six patients, lymphopenia in nine, and thrombocytopenia in six; other toxicities were rare. No dose-limiting toxicity was seen. Out of 18 evaluable patients 2 had a radiographic response (one partial and one minor). Disease was stable in 6 of 18 patients and the median survival was 27 weeks. This regimen was well tolerated and a phase II trial using a dose of 30 mg/m2 of vinorelbine is warranted.
authors.affiliation: Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, 10021, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Omuro
authors.forename: J J
authors.initials: JJ
authors.lastname: Raizer
authors.forename: A
authors.initials: A
authors.lastname: Demopoulos
authors.forename: M G
authors.initials: MG
authors.lastname: Malkin
authors.forename: L E
authors.initials: LE
authors.lastname: Abrey
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D000077204:Temozolomide; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D003606:Dacarbazine; D000077235:Vinorelbine; D000077204:Temozolomide