Phase II Trial of Temozolomide and Sorafenib in Advanced Melanoma Patients with or without Brain Metastases

被引:93
作者
Amaravadi, Ravi K.
Schuchter, Lynn M.
McDermott, David F. [3 ]
Kramer, Amy
Giles, Lydia
Gramlich, Kristi
Carberry, Mary
Troxel, Andrea B.
Letrero, Richard [2 ]
Nathanson, Katherine L. [2 ]
Atkins, Michael B. [3 ]
O'Dwyer, Peter J.
Flaherty, Keith T. [1 ]
机构
[1] Univ Penn, Dept Med, Abramson Canc Ctr, MD Dev Therapeut Program, Philadelphia, PA 19104 USA
[2] Univ Penn, Div Med Genet, Dept Med, Philadelphia, PA 19104 USA
[3] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA
关键词
STAGE-IV MELANOMA; MALIGNANT-MELANOMA; INTERFERON-ALPHA; DACARBAZINE; COMBINATION; PACLITAXEL; CANCER; INTERLEUKIN-2; CARBOPLATIN; CISPLATIN;
D O I
10.1158/1078-0432.CCR-09-2074
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: The combination of the oral alkylating agent temozolomide and the oral multikinase inhibitor sorafenib was evaluated in advanced melanoma patients. Experimental Design: Patients with metastatic melanoma (n = 167) were treated on four arms. All patients received sorafenib at 400 mg p.o. twice daily without interruption. Patients without brain metastases or prior temozolomide were randomized between arm A extended dosing of temozolomide (75 mg/m(2) temozolomide daily for 6 of every 8 weeks) and arm B: standard dosing (150 mg/m(2) temozolomide daily for 5 of every 28 days). Patients previously treated with temozolomide were enrolled on arm C: extended dosing of temozolomide. Patients with brain metastases and no prior temozolomide were assigned to arm D: standard dosing. The primary end point was 6-month progression-free survival (PFS) rate. Secondary end points included response rate, toxicity rates, and the rates of BRAF or NRAS mutations. Results: 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 to 4 lymphopenia in arm A. Conclusion: Temozolomide plus sorafenib was well tolerated and showed activity in melanoma patients without prior history of temozolomide. The activity of this combination regimen warrants further investigation. (Clin Cancer Res 2009;15(24):7711-8)
引用
收藏
页码:7711 / 7718
页数:8
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