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 pa-tients 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 regi-men of SUN (37.5 mg, d1-28) and TMZ (200 mg/m 2 , d1-5) was continued in a 28-days cycle until disease progres-sion 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 in-testinal lesion occurred in 4 patients, genitourinary lesion occurred in 9 patient, nasal lesions in 5 patient, oral le-sions in 7 patients and esophagal lesion in 2 patients; 19 patients had been previously treated with anti-tumor treat-ment. 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 de-tected 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 effec-tive and safe approach.

国家重点基础研究发展计划（973 计划）资助项目（No. 2013CB911004）