沙利度胺联合含烷化剂方案和非烷化剂方案治疗初发多发性骨髓瘤疗效比较

Comparison of therapeutic effect between thalidomide with and without alkylating agents on patients with new-onset multiple myeloma

目的观察沙利度胺分别联合含烷化剂方案和非烷化剂方案治疗多发性骨髓瘤（MM）的疗效。方法入选49例初发MM患者，按随机数字表法分为A、B两组，均给予沙利度胺100mg／d，每周增加50—100mg／d，直到200—300mg／d后进行维持治疗。其中A组（19例）再给予MP方案（美法仑2mg／次，3次／d，口服，第1天至第7天；泼尼松60mg／d口服，第1天至第7天）或COMP方案（环磷酰胺0．2g，第1天至第4天；长春新碱0．4mg，第1天至第4天；美法仑4mg／次，3次／d，口服，第1天至第5天；泼尼松60mg／d，口服，第1天至第5天）治疗；而B组（30例）则给予VAD方案（长春新碱0．4mg／d，第1天至第4天；表柔比星10mg／d，第1天至第4天；地塞米松40mg／d，口服或静脉滴注，第1天至第4天、第9天至第12天、第17天至第20天），28d为1个疗程，随后对两组的病情转归及不良反应进行分析。结果采用烷化剂治疗的A组总有效率73．7％（14／19），而非烷化剂治疗的B组总有效率53．3％（16／30）（χ^2=2．029，P=0．154），3年总生存率分别为52．6％（10／19）和53．3％（16／30），两组差异无统计学意义（χ^2=2．468，P=0．116）。A组的主要不良反应包括腹胀、便秘、乏力、周围神经病变、头晕、嗜睡、皮疹、水肿及血小板减少等，其发生率明显高于B组，但两组3—4级以上不良反应均较少见。结论沙利度胺联合烷化剂方案治疗初发MM与非烷化剂组早期疗效没有差别，药物毒副作用相对较多，不推荐作为初治患者的首选方案。

Objective To compare the efficacy and toxicity of thalidomide-COMP （T-COMP） and thalidomide-VAD （T-VAD） regimens in previously untreated multiple myeloma （MM） patients. Methods Forty-nine newly diagnosed MM patients were randomly allocated to either A group （thalidomide-MP/-COM16, 19 cases） or B group （thalidomide-VAD, 30 cases）. All patients received thalidomide 200 mg p.o. daily. Patients in group A received additionally vincristine 0.4 mg i.v. on day 1-4, cyclophosphamide 200 mg i.v. on day 1-4, melphalan 4 mg tid p.o. on days 1-5, prednisone 60 mg p.o. daily on days 1-5. Patients in group B received additionally vincristine 0.4 mg i.v. on day 1-4 and epirubicin 10 mg/m2 i.v., on day 1-4 and dexamethasone 40 mg p.o. daily on days 1-4, 9-12 and 17-20 for the first cycle and on days 1-4 for the next three cycles. Treatment was administered every 28 days. The therapeutic response was evaluated based on the International Myeloma Working Group Criteria （IMWG 2006） after the treatment..The toxicity was graded according to NCI common terminology criteria for adverse events v 3.0. Results On an intention-to-treat basis, at least partial therapeutic response was observed. The rates were 73.7 % and 53.3 % in group A and B respectively （χ2 = 2.029, P = 0.154）. Overall survival （OS） rate at 2 years were 52.6 % （10/19） in group A and 53.3 % （16/30） in group B, respectively （χ2 = 2.468, P = 0.116）. Considering overall toxicity, constipation, peripheral neuropathy, dizziness/somnolence, skin rash and edema were significantly higher in group B compared with group A, but the incidence of toxicities grade 3-4 was low and similar in both arms. Conclusion The overall response rate of T-MP/T-COMP regimen is similar with that of T-VAD regimen, suggesting this regimen cannot be chosen as the first treatment for patients with non-implantation therapy.