Dose-intensified bi-weekly temozolomide in patients with asymptomatic brain metastases from malignant melanoma: a phase II DeCOG/ADO study.

Abstract

BACKGROUND:

Temozolomide has shown some efficacy in metastatic melanoma and recently received extended approval to treat brain tumours. The purpose of this study was to test a dose-intensified regimen of temozolomide in melanoma patients with brain metastases in a prospective, open-label, multicentre phase II trial.

PATIENTS AND METHODS:

Forty-five patients with asymptomatic brain metastases from melanoma were stratified into arm A (no prior chemotherapy; n = 21) and arm B (previous chemotherapy; n = 24). Patients received oral temozolomide either 150 mg/m(2)/day (arm A) or 125 mg/m(2)/day (arm B), days 1-7 and 15-21, every 28 days. The primary study end point was objective response, and secondary end points were overall survival and safety.

RESULTS:

Two patients (4.4%) achieved a partial response (PR) in brain metastases (one in each arm), one of them (2.2%) also showing a PR in extracerebral disease. An additional five patients (11.1%; two in arm A, three in arm B) showed disease stabilisation (SD) in brain and other sites. However, 82% revealed progressive disease (PD) already evident 8 weeks after therapy initiation. Median survival time from therapy onset was 3.5 months (range 0.7-8.3; arm B) and 4.3 months (range 1.6-11.8; arm A), P = 0.43. Dose modifications and prolongations of therapy cycles due to toxicity were required in 20% of patients. Grade 3/4 toxicity was observed in one patient only (2.2%).

CONCLUSIONS:

Oral administration of temozolomide given bi-weekly is well-tolerated in melanoma patients with cerebral involvement. However, the efficacy is limited, with lower than 5% objective responses observed in brain and extracerebral metastases.

• Authors: D Schadendorf, A Hauschild, S Ugurel, A Thoelke, F Egberts, M Kreissig, R Linse, U Trefzer, T Vogt, W Tilgen, P Mohr, C Garbe
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 17 Issue 10 Pg. 1592-7 (Oct 2006) ISSN: 0923-7534 [Print] England
• PMID: 17005632 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Antineoplastic Agents, Alkylating
• Dacarbazine
• Temozolomide

Topics

• Adult
• Aged
• Antineoplastic Agents, Alkylating (administration & dosage, adverse effects)
• Brain Neoplasms (drug therapy, mortality, secondary)
• Dacarbazine (administration & dosage, adverse effects, analogs & derivatives)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Humans
• Male
• Melanoma (drug therapy, mortality, pathology)
• Middle Aged
• Skin Neoplasms (drug therapy, mortality, pathology)
• Survival Analysis
• Temozolomide
• Treatment Outcome