大剂量干扰素辅助治疗国人口腔粘膜恶性黑色素瘤的临床研究

Clinical study on high-dose interferon alpha-2b adjuvant treatment in Chinese oral mucosal malignant melanoma

目的：探讨大剂量干扰素辅助治疗口腔粘膜恶性黑色素瘤的疗效和安全性。方法回顾性分析2004年5月至2012年11月我科经治的Ⅲ～ⅣA期口腔粘膜恶性黑色素瘤患者的治疗及预后情况。在经治的117例患者中，73例术后接受了大剂量干扰素α-2b治疗，其中有58例完成了治疗计划，设为治疗组，另15例中途停止；其余44例未采用大剂量干扰素治疗者作为对照组。比较两组患者的总生存期（ OS）和无复发生存期（ RFS）以及相关不良反应的发生情况。结果117例患者的中位OS为40个月（95％CI：33～62个月）。治疗组与对照组中Ⅲ期患者的中位OS（69个月vs．65个月）和RFS（50个月vs．34个月）的差异均无统计学意义（P＞0.05），治疗组与对照组中ⅣA期患者的中位OS（37个月 vs．20个月）和中位RFS（33个月 vs．10个月）的差异均有统计学意义（ P＜0.05），治疗组与对照组中Ⅳ期伴颈淋巴结转移患者的中位OS（40个月vs．20个月）和中位RFS（33个月 vs．10个月）的差异均有统计学意义（P＜0.05）。大剂量干扰素治疗的常见血液学毒性为骨髓抑制，包括白细胞减少和血小板减少；非血液性不良反应包括流感样症状、恶心呕吐、肝功能损害等。全组患者不良反应以1～2级为主，仅有7例出现3～4级毒副反应，给予对症治疗后均能缓解，无治疗相关性死亡。结论术后大剂量干扰素辅助治疗能显著提高ⅣA期口腔粘膜恶性黑色素瘤患者的OS和RFS，且治疗的不良反应可耐受。

Objective To investigate the therapeutic effects and main side effects of high-dose interferon alpha-2b （ IFN-α-2b） adjuvant treatment in Chinese oral mucosal melanoma. Methods A total of 117 patients with oral mucosal melanomas with stageⅢ-ⅣA after surgery from May 2004 to November 2012 were analyzed retrospectively. In the 117 cases of oral mucosal melanoma, 73 cases received the adjuvant therapy of high-dose IFN-α-2b, of whom 58 cases finished the treatment（ treatment group） and 15 cases discontinued treatment. The rest 44 cases who didn＆#39;t receive high-dose IFN-α-2b adjuvant treatment were selected as the control group. The overall survival（ OS） , relapse-free survival（ RFS） and side effects between the two groups were compared. Results The median OS of 117cases was 40 months（95%CI：33-62months）. For the patients with stage Ⅲ, the differences of median OS（69 months vs.65 months） and RFS（50 months vs.34 months） were not significant between the two groups. While those of cases with stageⅣA had sig-nificant differences, the median OS was 37 months vs. 20 months（ P=0？028） , and the RFS was 33 months vs. 10 months（ P=0？004） . Furthermore, the benefit of treatment was greater for those of cervical lymph nodes involved in the patients with stageⅣA. The median OS was 40 months vs. 20 months, the median RFS was 33 months vs. 10 months. Adverse reactions occurred in most patients treated with high-dose IFN-α-2b. The common hematology toxicity was bone marrow suppression, including low counts of white blood cells and platelets. The other side-effects included drug-induced influenza-like syndrome, gastrointestinal responses and liver function damage.Toxicity of grade 1-2 was predominant, only 7 cases had grade 3-4 toxicity. After given symptomatic treatment, all of them could be re-lieved. No treatment-related death happened. Conclusion High-dose IFN-α-2b adjuvant treatment may improve overall survival time as well as relapse-free survival time in patients with advanced oral mucosal melanoma（ stage ⅣA） ,and the side effects are tolerable.