Phase II Trial of Temozolomide and Sorafenib in Advanced Melanoma Patients with or without Brain Metastases.
Phase II Trial of Temozolomide and Sorafenib in Advanced Melanoma Patients with or without Brain Metastases.
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DOI：
10.1158/1078-0432.ccr-09-2074
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发表时间：
2009-12-15
期刊：
影响因子：
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通讯作者：
Flaherty KT
中科院分区：
文献类型：
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作者：
Amaravadi RK;Schuchter LM;McDermott DF;Kramer A;Giles L;Gramlich K;Carberry M;Troxel AB;Letrero R;Nathanson KL;Atkins MB;O'Dwyer PJ;Flaherty KT
The combination of the oral alkylating agent temozolomide and the oral multi-kinase inhibitor sorafenib was evaluated in advanced melanoma patients. Patients with metastatic melanoma (N=167) were treated on four arms. All patients received sorafenib at 400 mg orally twice daily without interruption. Patients without brain metastases or prior temozolomide were randomized between Arm A: extended dosing of temozolomide (EDT; 75 mg/m2 temozolomide daily for 6/8 weeks) and Arm B: standard dosing (SDT; 150 mg/m2 temozolomide daily for 5/28 days). Patients previously treated with temozolomide were enrolled on Arm C: EDT. Patients with brain metastases and no prior temozolomide were assigned to Arm D: SDT. The primary endpoint was 6-month progression-free survival (PFS) rate. Secondary endpoints included response rate, toxicity rates, and the rates of BRAF or NRAS mutations. The 6-month PFS rate for arms A, B, C, and D were 50%, 40%, 11%, and 23%. The median PFS for patients on arm A, B, C, and D was 5.9, 4.2, 2.2, and 3.5 months, respectively. No significant differences were observed between Arms A and B in 6-month PFS rate, median PFS, or response rates. Treatment was well tolerated in all arms. No significant differences in toxicity were observed between arms A and B except for more grade 3–4 lymphopenia in arm A. Temozolomide plus sorafenib was well tolerated and demonstrated activity in melanoma patients without prior history of temozolomide. The activity of this combination regimen warrants further investigation.
