Dimopoulos M A, Pouli A, Zervas K, Grigoraki V, Symeonidis A, Repoussis P, Mitsouli C, Papanastasiou C, Margaritis D, Tokmaktsis A, Katodritou I, Kokkini G, Terpos E, Vyniou N, Tzilianos M, Chatzivassili A, Kyrtsonis M C, Panayiotidis P, Maniatis A
Department of Clinical Therapeutics and Internal Medicine, University of Athens School of Medicine, Athens, Greece.
Ann Oncol. 2003 Jul;14(7):1039-44. doi: 10.1093/annonc/mdg287.
The combination of vincristine and doxorubicin administered as a continuous infusion via an indwelling catheter together with intermittent high-dose dexamethasone (VAD) is an effective primary treatment for patients with symptomatic multiple myeloma. In order to avoid the need for an indwelling catheter, which imposes logistic problems for outpatient administration, several phase II studies have explored the feasibility and efficacy of VAD-like outpatient regimens. We designed a prospective randomized study to compare the objective response rates of two VAD-like outpatient regimens as primary treatment for symptomatic patients with multiple myeloma.
Patients were entered in a randomized study regardless of age, performance status and renal function. One hundred and twenty-seven patients received VAD bolus, which consisted of vincristine 0.4 mg i.v., doxorubicin 9 mg/m(2) i.v. and dexamethasone 40 mg p.o. daily for four consecutive days and 132 patients received VAD doxil, which consisted of vincristine 2 mg i.v. and liposomal doxorubicin 40 mg/m(2) i.v. on day 1 and dexamethasone 40 mg p.o. daily for 4 days. The two regimens were administered every 28 days for four courses and in courses 1 and 3, in both arms, dexamethasone was also given on days 9-12 and 17-20.
An objective response was documented in 61.4% and 61.3% of patients treated with VAD bolus and VAD doxil, respectively. Hematological and non-hematological toxicities were mild or moderate and equally distributed between the two treatment arms with the exception of alopecia, which was more common after VAD bolus, and of palmar-plantar erythrodysesthesia, which was more common after VAD doxil.
Our multicenter trial, which included an unselected patient population, indicated that both VAD bolus and VAD doxil can be administered to outpatients and can provide an equal opportunity of rapid response in many patients with multiple myeloma.
长春新碱与阿霉素通过留置导管持续输注并联合间歇性大剂量地塞米松（VAD）进行治疗，是有症状的多发性骨髓瘤患者有效的一线治疗方案。为了避免使用留置导管带来的后勤问题（这给门诊给药带来了困难），多项II期研究探索了类似VAD的门诊治疗方案的可行性和疗效。我们设计了一项前瞻性随机研究，比较两种类似VAD的门诊治疗方案作为有症状的多发性骨髓瘤患者一线治疗的客观缓解率。
患者无论年龄、身体状况和肾功能如何，均可参加随机研究。127例患者接受VAD推注方案，即静脉注射长春新碱0.4mg、阿霉素9mg/m²，口服地塞米松40mg，连续4天每日给药；132例患者接受VAD多柔比星脂质体方案，即第1天静脉注射长春新碱2mg和脂质体阿霉素40mg/m²，口服地塞米松40mg，连续4天每日给药。两种方案每28天给药一次，共进行四个疗程，在第1和第3疗程中，两组患者在第9 - 12天和第17 - 20天也给予地塞米松。
接受VAD推注方案和VAD多柔比星脂质体方案治疗的患者中，分别有61.4%和61.3%记录到客观缓解。血液学和非血液学毒性均为轻度或中度，除脱发（在VAD推注方案后更常见）和手足红斑感觉异常（在VAD多柔比星脂质体方案后更常见）外，两种治疗组之间毒性分布相同。
我们的多中心试验纳入了未经选择的患者群体，结果表明VAD推注方案和VAD多柔比星脂质体方案均可用于门诊患者，并且可以为许多多发性骨髓瘤患者提供同等的快速缓解机会。
