© 2006 European Society for Medical Oncology
sarcomas and melanoma |
Dose-intensified bi-weekly temozolomide in patients with asymptomatic brain metastases from malignant melanoma: a phase II DeCOG/ADO study
1 Skin Cancer Unit, German Cancer Research Center & University Hospital Mannheim, Department of Dermatology
2 University Hospital, Kiel
3 University Hospital, Tübingen
4 Community Hospital, Erfurt
5 Charite Hospital, Humboldt University, Berlin
6 University Hospital, Regensburg
7 University Hospital, Homburg
8 Elbe Hospital, Buxtehude, Germany
*Correspondence to: Dr D. Schadendorf, Skin Cancer Unit, German Cancer Research Center & University Hospital Mannheim, Theodor Kutzer Ufer 1, D-68135 Mannheim, Germany. Tel: +49-621-383-2126; Fax: +49-621-383-2163; E-mail: d.schadendorf{at}dkfz.de
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/m2/day (arm A) or 125 mg/m2/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.
Key words: temozolomide, brain metastases, metastatic melanoma