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目的伊马替尼已经改变了c-Kit的晚期黑色素瘤的治疗模式,但在辅助治疗中尚无尝试。我们开展这项临床研究(NCT01782508),旨在比较伊马替尼和大剂量干扰素(HDI)在c-Kit突变的术后高危患者中的疗效及安全性。方法 48例存在c-Kit 9、11或13号外显子突变的高危黑色素瘤患者被纳入此项研究,并随机(1∶2)分入伊马替尼组(400 mg/d)或HDI组(15×106 U/m2 d1~d5/周×4周,之后9×106 U,每周3次×48周)。主要终点指标为无复发生存期(RFS),次要终点指标为无远处转移生存时间(DMFS)、总生存时间(OS)及耐受性。结果最常见的c-Kit突变为c-KitL576P(13/48)。截至2015年10月,HDI组中的中位RFS为29.8个月(95%CI 23.3~36.3个月),明显优于伊马替尼组(10.0个月;95%CI 0~20.0个月)(P=0.029)。在c-KitL576P突变的患者中观察到类似的趋势(P=0.005)(伊马替尼组仅4.8个月,而HDI组达34.2个月)。两组患者的预计OS相似(P=0.43)。在HDI组中记录到更多的3~4度不良反应。结论在此项研究中,伊马替尼与HDI相比并未延长c-Kit突变高危黑色素瘤患者的RFS。伊马替尼可能不适合被推荐单独用于c-Kit突变高危黑色素瘤患者的辅助治疗。
Purpose imatinib has altered the mode of treatment of advanced melanoma in c-Kit, but no attempt has been made in adjuvant therapy. We conducted this clinical study (NCT01782508) to compare the efficacy and safety of imatinib and high-dose interferon (HDI) in postoperative high-risk patients with c-Kit mutations. Methods Forty-eight patients with high-risk melanoma with mutations in c-Kit 9, 11, or 13 exon were included in this study and randomized (1: 2) to imatinib (400 mg / d) or HDI (15 × 106 U / m2 d1-d5 / week × 4 weeks, followed by 9 × 106 U, 3 times per week × 48 weeks). The primary end point was no recurrence (RFS) and the secondary end point was no distant metastasis (DMFS), overall survival (OS), and endurance. Results The most common c-Kit mutation was c-KitL576P (13/48). As of October 2015, the median RFS in the HDI group was 29.8 months (95% CI 23.3 to 36.3 months), significantly better than the imatinib group (10.0 months; 95% CI, 0-20.0 months) (P = 0.029). A similar trend was observed in patients with c-KitL576P mutation (P = 0.005) (only 4.8 months in the imatinib group versus 34.2 months in the HDI group). The expected OS was similar between the two groups (P = .43). In the HDI group recorded more 3 to 4 degrees of adverse reactions. Conclusion In this study, imatinib did not prolong the RFS in c-Kit mutation-prone melanoma patients compared with HDI. Imatinib may not be suitable for adjuvant therapy alone in patients with c-Kit mutations at high risk of melanoma.