晚期黑素瘤过继免疫治疗的Ⅱ期临床研究

Phase Ⅱ study of adoptive immunotherapy for advanced melanoma

目的:观察化疗联合细胞因子诱导的杀伤细胞(cytokine induced killer,CIK)治疗转移性恶性黑素瘤(metastatic melanoma,MM)的疗效及其安全性。方法:53例MM患者接受福莫司汀100mg/m2,第1～5天;氮烯咪胺400mg/d,第2～6天;CIK第7、14、和16天;每28d为1个周期的联合治疗,每2个周期评价疗效。结果:34例可评价患者中完全缓解(com-plete response,CR)1例(2.9%),部分缓解(partial response,PR)7例(20.6%),总有效率(overall response,ORR)为23.5%;疾病稳定(stable disease,SD)14例(44%),临床获益率(clinical benefit rate,CBR)67.5%;中位无进展生存期(progressionfree survival,PFS)8个月;中位总生存期(overall survival,OS)11个月;乳酸脱氢酶(lactate dehydrogenase,LDH)正常者的OS长于升高者;有效或稳定患者的PFS和OS长于疾病进展(progression disease,PD)患者。不良反应中G3+G4血小板减少41%,白细胞减少23.5%;发生2例超敏反应。无治疗相关死亡。结论:化疗联合CIK治疗MM患者耐受性尚好,有效率高于常规化疗,可延长LDH升高和疗效评价未PD患者的生存时间,但仍有待Ⅲ期临床研究进一步验证。

Objective：To observe the efficacy and safety of chemotherapy combined with cytokine-induced killer （CIK） cells in the treatment of metastatic melanoma （MM）. Methods： Fifty three chemotherapy-naive MM patients were administered fotemustine at 100 mg/m^2 on d 1-5 ; dacarbazine were given at 400 mg/d on d 2-6 ; CIK were infused on d 7, d 14, d 16. Twenty-eight days were regarded as one cycle. The clinical efficay was evaluated every 2 cycles. Results：Thirty-four out of 53 patients were eligible to be evaluated. The overall response rate （ORR） was 23.5% including 1 case with complete response （CR） （2.9%） and 7 cases with partial response （PR） （20.6%）. Fourteen cases had stable disease （44%）. The clinical benefit response was 67.5%. Median progression free survival （PFS） was 8 months. Median overall survival （OS） was 11 months. The patients with normal lactate dehydrogenase （LDH） had longer OS; those with stable disease had longer PFS and OS. Adverse reaction included grade Ⅲ/Ⅳ thrombopenia （41% ）, decrease in the number of WBC （23.5%）, and hyperreactivity （2 cases）. No treatment-related death occurred. Conclusion： Chemotherapy followed by the infusion of CIK was tolerable. The response rate was higher than common chemotherapy. It could prolong the survival time of tumor patients with elevated LDH and non progression disease. Phase HI study is needed to confirm the results.