Temozolomide, thalidomide, and whole brain radiation therapy for patients with brain metastasis from metastatic melanoma: a phase II Cytokine Working Group study.

Atkins MB, Sosman JA, Agarwala S, Logan T, Clark JI, Ernstoff MS, Lawson D, Dutcher JP, Weiss G, Curti B, Margolin KA
Cancer. 2008 113 (8): 2139-45

PMID: 18792064 · DOI:10.1002/cncr.23805

BACKGROUND - The combination of temozolomide (TMZ) and thalidomide was reported to produce a high response rate, including shrinkage of brain metastases, in patients with metastatic melanoma. The authors tested the efficacy of a regimen including TMZ, thalidomide, and whole brain radiation therapy (WBRT) in patients with brain (CNS) metastases from melanoma.

METHODS - Patients with melanoma, CNS metastases documented by magnetic resonance imaging, and no prior systemic chemotherapy received WBRT, 30 Gray in 10 fractions, Days 1 to 5 and 8 to 12; TMZ, 75 mg/m(2)/day, Weeks 1 to 6; and thalidomide, 100 mg/day, Weeks 1 to 4, then escalated by 100 mg/day at Weeks 5, 7, and 9 as tolerated to a maximum of 400 mg/day. CNS and systemic tumor response was assessed at Week 10. Patients without CNS or clinically significant systemic disease progression received additional cycles of TMZ at 10-week intervals.

RESULTS - Thirty-nine patients received treatment, and 3 exhibited CNS response (1 complete response, 2 partial responses) (response rate, 7.6%; 95% confidence interval, 0.7%-16.1%), all unconfirmed by repeat imaging. Seven patients had stable CNS disease at 10 weeks. No patient exhibited a systemic response. Only 4 patients received 2 cycles of therapy, and just 1 received 3. Median time to progression was 7 weeks, and median overall survival was 4 months. Grade 3-4 side effects included deep venous thrombosis (3), pulmonary embolism (1), and CNS events (12). Eighteen (45%) patients required admission for side effects (7) and/or symptomatic disease progression (11).

CONCLUSIONS - The efficacy of TMZ, thalidomide, and WBRT in the treatment of CNS metastatic melanoma is low. Other treatment approaches should be considered for this patient population.

(c) 2008 American Cancer Society.

MeSH Terms (15)

Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols Brain Neoplasms Combined Modality Therapy Cranial Irradiation Dacarbazine Female Humans Male Melanoma Middle Aged Temozolomide Thalidomide

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