中国黑色素瘤患者对大剂量干扰素辅助治疗的耐受性观察

The Tolerability of Chinese Melanoma Patients to High-dose Interferon Adjuvant Therapy

目的:观察中国人对4周大剂量干扰素IFNα-2b(甘乐能)方案辅助治疗恶性黑色素瘤的耐受性。方法:回顾性分析2007年9月至2009年5月在本院诊治的29例高危恶性黑色素瘤(AJCC分期为Ⅱb～Ⅲc期)患者,采用大剂量干扰素IFNα-2b4周治疗方案,每天剂量为(2200～3375U单位),每周连续静脉输注5天,休息2天,共用4周,观察不良反应以及早期进展情况。不良反应评定采用美国国家癌症研究所常用毒性评定标准NCI2.0版本。结果:全部29例患者接受大剂量干扰素治疗,患者平均接受干扰素的治疗强度为17.63U单位/(m^2·d)。全部患者均接受毒性反应评价,2例患者未完成4周干扰素治疗,其中1例因术后伤口愈合不良仅进行了1周治疗,而另1例因重度疲劳无法完成第4周治疗;其余27例患者均完成4周大剂量干扰素治疗。不良反应主要以一过性骨髓抑制为主,69%(20/29)曾经出现3～4度中性粒细胞下降者,常规处理后迅速恢复,另有62%(18/29)患者出现1～2度肝转氨酶升高,无肝毒性相关性死亡。26例患者接受随访超过3个月,5例在干扰素治疗开始3个月内进展者,分别为局部复发1例,区域淋巴结转移2例,患肢皮下过路转移1例,远处转移1例。结论:中国人能耐受大剂量干扰素IFNα-2b辅助治疗,但大剂量干扰素似乎不能有效抑制亚临床病灶。

Objective： To observe the tolerability of Chinese melanoma patients to four-week high-dose interferon alfa-2b （INTRON A, Schering-Plough） therapy. Methods： A total of 29 patients with high risk melanoma [American Joint Committee on Cancer Staging （AJCC） ⅡB-ⅢC] who received adjuvant interferon therapy in our hospital between September 2007 and May 2009 were retrospectively reviewed. Patients received 4 hours of intravenous infusion of interferon alfa-2b [dose range, 22.00 million international unit （MIU） to 33.75 MIU] IV 5 days/week for 4 weeks. The adverse events were evaluated with National Cancer Institute Common Toxicity Criteria （NCI 2.0 version）. Results： The average daily dose was 17.63 MIU/（m^2·d）. The therapy was ended in two patients because of poor wound healing or intolerability to severe fatigue. The most common adverse events were myelosuppression. Grade 3/4 neutropenia was observed in 69% （20/29） patients and was rapidly reversed after conventional support interventions. Grade 1/2 abnormal hepatic function occurred in 18 cases （62%）. Twenty-six patients were followed up for 3 to 22 months. Five patients developed early progression： one with local recurrence, two with regional lymph node metastasis, one with in-transit metastasis in the affected limb, and one with distant metastasis. Conclusion： High-dose interferon alfa-2b regimen can be well tolerated by Chinese patients but cannot effectively inhibit subclinical lesions.