替莫唑胺联合舒尼替尼治疗转移性黏膜黑色素瘤的疗效及安全性

Efficacy and safety analysis of temozolomide combined with sunitinib in treatment of metastatic mucosal melanoma

目的:探索替莫唑胺(temozolomide,TMZ)联合舒尼替尼(sunitinib,SUN)在转移性黏膜黑色素瘤治疗中的应用价值。方法:回顾性纳入我中心2008年8月至2016年12月间接受TMZ联合SUN治疗的晚期黏膜黑色素瘤患者。患者均无BRAF/NRAS突变,服用TMZ(200 mg/m^2,d 1~5)和SUN(37.5 mg,d 1~28)治疗,28 d为一个疗程,治疗直至病情进展或毒副反应无法耐受。主要观察客观有效率(ORR)、疾病无进展生存期(PFS)、总生存期(OS)和毒副反应发生率。结果:纳入的27例患者中,原发肠道4例、泌尿生殖道9例、鼻咽部5例、口腔7例、食管2例,有19例患者既往接受过抗肿瘤治疗,TMZ联合SUN治疗的中位治疗周期为3.0。治疗后ORR 19.2%,疾病控制率(DCR)81.5%,中位PFS(3.0±0.7)个月,中位OS(7.1±0.9)个月。全组患者中有4例存在KIT突变,提示存在KIT突变/扩增的患者使用KIT抑制剂可能获益。联合治疗耐受性良好,仅2例患者因出现血小板抑制Ⅳ级,将SUN调整剂量为25 mg。Ⅲ~Ⅳ级副反应包括血小板下降(19.2%)、白细胞下降(19.2%)和肝功能损害(3.9%),未发生治疗相关性死亡事件。结论:TMZ联合SUN是治疗转移性黏膜黑色素瘤的有效方案,且安全性良好。

Objective： To investigate the application value of temozolomide（TMZ） combined with sunitinib（SUN）in the treatment of metastatic mucosal melanoma. Methods： This research retrospectively analyzed the data of patients with metastatic mucosal melanoma that treated with TMZ combined with SUN in Peking University Cancer Hospital from August, 2008 to December, 2016. Patients showed no BRAF/NRAS mutation. The combination regimen of SUN（37.5 mg, d1-28） and TMZ（200 mg/m^2, d1-5） was continued in a 28-days cycle until disease progression or toxicity intolerance. The primary observation indices were objective response rate（ORR）, progression-free survival（PFS）, overall survival（OS） and toxic side effect rate. Results： Among the included 27 patients, primary intestinal lesion occurred in 4 patients, genitourinary lesion occurred in 9 patient, nasal lesions in 5 patient, oral lesions in 7 patients and esophagal lesion in 2 patients; 19 patients had been previously treated with anti-tumor treatment. Median treatment cycle was 3.0 of TMZ combined with SUN treatment. ORR was 19.2%, disease control rate was 81.5%, median PFS and OS were（3.0±0.7） months and（7.1±0.9） months, respectively. KIT mutation was detected in 4 patients, and the use of KIT inhibitor might be beneficial to those patients. The combination therapy was well tolerated, and only 2 patients required a dose reduction of SUN to 25 mg due to thrombocytopenia（grade Ⅳ）.Grade Ⅲ-Ⅳ toxicities mainly included thrombocytopenia（19.2%）, leucopenia（19.2%）, and hepatic injury（3.9%）.No treatment related death occurred. Conclusion： For metastatic mucosal melanoma, TMZ＋SUN might be an effective and safe approach.