DVD和PAD方案治疗初治多发性骨髓瘤的疗效分析

Efficacy of DVD and PAD regimens in patients with newly diagnosed multiple myeloma

目的:观察DVD方案(脂质体阿霉素、长春新碱或长春地辛、地塞米松)和PAD方案(硼替佐米、脂质体阿霉素、地塞米松)治疗初治多发性骨髓瘤(MM)的近期疗效和不良反应。方法:初治MM患者50例,其中DVD组和PAD组各25例。DVD方案:D(脂质体阿霉素)40mg/m2,静脉滴注,第1天;V(长春新碱)2.0mg或(长春地辛)4.0mg,静脉注射,第1天;D(地塞米松)40mg/d,静脉或口服,连用4天;每4周为1个周期。PAD方案:P(硼替佐米,万珂)1.3mg/m2,静脉注射,第1、4、8、11天;A(脂质体阿霉素)20mg,静脉滴注,第1、4、8天;D(地塞米松)20mg/d,静脉滴注,第1、4、8、11天;每4周为1个周期。采用IMWG标准观察疗效,并按NCI CTCAE(第3版)标准判断不良反应。结果:DVD组患者接受平均4.5(2~8)个周期的治疗,完全缓解(CR)4例(16%),非常好的部分缓解(VGPR)3例(12%),部分缓解(PR)10例(40%),总反应(CR+VGPR+PR)率为68%。此外,疾病稳定(SD)5例(20%),疾病进展(PD)3例(12%),疾病控制(CR+VGPR+PR+SD)率为88%。初始疗效的中位时间为5(3~12)周,最佳疗效的中位时间为4(1~6)个月。最常见的不良反应为胃肠道症状,其中10例(40%)有轻微恶心,9例(36%)出现便秘。其次为血液学改变,中性粒细胞减少7例(28%),贫血6例(24%),血小板减少4例(16%)。手掌-脚底异常感觉、红斑4例(16%),黏膜炎2例(8%)。PAD组患者接受平均3.8(2~7)个周期的治疗,CR 13例(52%),VGPR 2例(8%),PR 7例(28%),总反应率为88%。此外,SD 3例(12%),疾病控制率为100%。初始疗效的中位时间为3(1~5)周,最佳疗效的中位时间为3(1~5)个月。最常见的不良反应为胃肠道症状,其中便秘9例(36%),腹泻2例(8%),恶心2例(8%),黏膜炎1例(4%)。其次为血液学改变,中性粒细胞减少7例(28%),贫血3例(12%),血小板减少6例(24%)。另外,周围神经病变较为多见,1/2级5例(20%),3级1例(4%)。5例(20%)出现手足综合征,3例(12%)出现乏力。2组比较,PAD组的总反应率和CR率明显高于DVD组(均P<0.01)。结论:PAD方案治疗初治MM近期疗效明显优于DVD方案,二者不良反应均较少,但PAD方案周围神经病变较为多见。

Objective：To investigate the efficacy and toxicity of DVD and PAD regimens in patients with newly diagnosed multiple myeloma （MM）. Method： Totally fifty patients with newly diagnosed MM were divided into DVD group （n=25） and PAD group （n 25）. Patients in DVD group were treated with DVD scheme （Pegylated liposomal doxorubicin 40 mg/m2 , Vincristine 2.0 mg or Vindesine 4.0 mg intravenously on the first day, Dexam- ethasone 40 mg/d intravenously or orally on days 1--4. Treatment was repeated every 4 weeks. Patients in PAD group were treated with PAD scheme （Bortezomib 1.3 mg/me intravenously on day 1,4,8, i1, Pegylated liposomal doxorubicin 20 nag intravenously on day 1,4,8, Dexamethasone 20 mg/d intravenously on day 1,4,8,11 ）. Treat- ment was repeated every 4 weeks. Response was evaluated according to the International Uniform Response Crite- ria for MM. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, ver- sion 3.0. Result：The median DVD cycles were 4.5（2--8）. The overall response rate （ORR） of DVD scheme was 68 ~/00, including complete response （CR） in 4 （ 16 ~ ）, very good partial response （VGPR） in 3 （ 12 ~ ）, partial re- sponse （PR） in 10（40~/00）. While the stable disease （SD） in 5（20~/oo） ,progression disease （PD） in 3（12%） ,the dis- ease control rate was 88%. The median time to initial response was 5（3--12） weeks and the median time to the best response was 4（1--6） months. The most common adverse events were gastrointestinal symptoms [nausea in 10（40%）,constipation in 9（36~）]. Neutropenia was in 7 patients （28%）,anemia was in 6 patients （24%） and thrombocytopenia was in 4 patients （16 %）. DVD was associated with hand foot syndrome （4 patients, 16 %） and mucitis （2 patients, 8 % ）. The median PAD cycles were 3.8 （2--7）. The ORR of PAD regimen was 88%, including CR in 13（52%）,VGPR in 2（8%） ,PR in 7（28%） and SD in 3（12%）. The disease control rate was 100%. The me-dian time to initial response was 3 （1--5） weeks and the median time to the best response was 3 （1--5） months. The most common adverse events were gastrointestinal symptoms constipation in 9 （36 % ）, diarrhea in 2 （8 % ）, mucositis in 1 （4 % ）, and nausea in 2 （8 % ） cases3. Hematologic adverse events included neutropenia （ 7 patients, 28% ）, anemia （ 3 patients, 12 % ） and thrombocytopenia （6 patients, 24 % ）. PAD was associated with more periph- eral neuropathy,grade 1/2 in 5 cases （20G） and grade 3 in 1 case （4G）. Hand foot syndrome was observed in 5 patients （20G）. Fatigue was observed in 3 patients （12G）. The ORR and CR of PAD scheme were significantly higher than those of DVD scheme （P~ 0. 01 ）. Con^lusion~ PAD scheme is a more effective therapy than DVD scheme in patients with newly diagnosed MM. The adverse events are mild in two schemes, but PAD is associated with more peripheral peripheral neuropathy.