Vinorelbine combined with a protracted course of temozolomide for recurrent brain metastases: A phase I trial Journal Article


Authors: Omuro, A. M.; Raizer, J. J.; Demopoulos, A.; Malkin, M. G.; Abrey, L. E.
Article 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. © Springer Science+Business Media, Inc. 2006.
Keywords: adult; clinical article; controlled study; treatment outcome; aged; disease-free survival; middle aged; overall survival; clinical trial; drug tolerability; fatigue; neutropenia; hypophosphatemia; liver dysfunction; paclitaxel; chemotherapy; temozolomide; nuclear magnetic resonance imaging; follow up; brain neoplasms; endometrium cancer; anorexia; carboplatin; dacarbazine; controlled clinical trial; breast cancer; anemia; bone marrow suppression; blood toxicity; lung non small cell cancer; nausea; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; carcinoma, non-small-cell lung; lung neoplasms; peripheral neuropathy; drug administration schedule; antineoplastic agents, phytogenic; cohort analysis; lung cancer; dose-response relationship, drug; breast neoplasms; vinblastine; drug fever; hyperglycemia; lymphocytopenia; syncope; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; confusion; drug fatality; hypermagnesemia; hyponatremia; prothrombin time; depression; lung small cell cancer; tumor recurrence; drug response; antineoplastic agents, alkylating; brain metastasis; muscle weakness; seizure; headache; maximum tolerated dose; phase 1 clinical trial; kidney cancer; navelbine; speech disorder; ataxia; lymphopenia; mood disorder; hypocalcemia; heart supraventricular arrhythmia; vinorelbine; brain radiography
Journal Title: Journal of Neuro-Oncology
Volume: 78
Issue: 3
ISSN: 0167-594X
Publisher: Springer  
Date Published: 2006-07-01
Start Page: 277
End Page: 280
Language: English
DOI: 10.1007/s11060-005-9095-8
PUBMED: 16614943
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 21" - "Export Date: 4 June 2012" - "CODEN: JNODD" - "Source: Scopus"
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MSK Authors
  1. Jeffrey J Raizer
    22 Raizer
  2. Antonio Marcilio Padula Omuro
    200 Omuro
  3. Mark Malkin
    38 Malkin
  4. Lauren E Abrey
    276 Abrey