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Phase II study of temozolomide and thalidomide in patients with metastatic melanoma in the brain†
High rate of thromboembolic events (CALGB 500102)
Article first published online: 19 SEP 2006
Copyright © 2006 American Cancer Society
Volume 107, Issue 8, pages 1883–1890, 15 October 2006
How to Cite
Krown, S. E., Niedzwiecki, D., Hwu, W.-J., Hodgson, L., Houghton, A. N., Haluska, F. G. and for the Cancer and Leukemia Group B (2006), Phase II study of temozolomide and thalidomide in patients with metastatic melanoma in the brain. Cancer, 107: 1883–1890. doi: 10.1002/cncr.22239
The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.
- Issue published online: 3 OCT 2006
- Article first published online: 19 SEP 2006
- Manuscript Accepted: 9 AUG 2006
- Manuscript Revised: 20 JUL 2006
- Manuscript Received: 9 MAY 2006
- National Cancer Institute. Grant Numbers: (CA31946), (CA77651), (CA33601), CA12449)
- malignant melanoma;
- brain metastases;
Preliminary studies suggesting that extended-dose temozolomide with thalidomide is safe and active in patients with metastatic melanoma have led to frequent use of this oral regimen. To confirm these observations the combination was tested in a multicenter Phase II trial in patients with melanoma brain metastases.
Eligible patients had melanoma brain metastases, with or without systemic metastases. The primary endpoint was response rate in brain metastases. Patients received temozolomide at a dose of 75 mg/m2/day for 6 weeks with a 2-week rest between cycles, and thalidomide (escalated to 400 mg/day for patients age <70 years or to 200 mg/day for patients age ≥70 years). A 2-stage design required ≥3 responses in the first 21 patients before enrolling 29 additional patients in the second stage.
Sixteen eligible patients were enrolled. No objective responses were observed. The median survival was 23.9 weeks. Seven patients withdrew because of tumor progression; 7 were removed during Cycle 1 because of adverse events, including allergic reaction (1 patient), severe fatigue (1 patient), sudden death (1 patient), and thromboembolic events (pulmonary embolism in 3 patients and deep vein thrombosis in 1 patient); 2 patients withdrew when the study was suspended and subsequently closed. No associations could be established between baseline characteristics and toxicity.
The proportion of patients with lethal or potentially life-threatening adverse events was high (0.31, 95% confidence interval, 0.11–0.59), and the absence of objective responses made it unlikely that further accrual would demonstrate the efficacy of the regimen. These observations provide little support for the use of this combination for melanoma brain metastases unless safe and effective methods to prevent thrombosis are developed. Cancer 2006. © 2006 American Cancer Society.