Thomson D B, Adena M, McLeod G R, Hersey P, Gill P G, Coates A S, Olver I N, Kefford R F, Lowenthal R M, Beadle G F
Melanoma Clinic, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia.
Melanoma Res. 1993 Apr;3(2):133-8.
Following extensive phase II trials of the combination of dacarbazine and interferon-alpha 2a we performed a prospective, randomized, controlled trial of this combination versus dacarbazine alone as systemic therapy for symptomatic, measurable metastatic malignant melanoma. The two treatment arms were well matched for age, sex, performance, status, relapse-free survival, prior therapy and sites of disease. Therapy consisted of dacarbazine given in combination in escalating doses of 200 mg/m2, 400 mg/m2 and 800 mg/m2 i.v. every 3 weeks, or alone at 800 mg/m2 i.v. every 3 weeks. Interferon was administered subcutaneously starting at 3 mU daily on days 1-3, 9 mU daily on days 4-70, then 9 mU three times per week. Therapy was continued for at least 6 months unless overt progressive disease was observed. Eighty seven patients were randomized to the combination and 83 patients to dacarbazine alone. Response rates were respectively, complete 7% and 2%, and partial 14% and 15%, for a total response rate of 21% (95% confidence limits 13-31%) and 17% (95% confidence limits 10-27%). Median duration of response was 258 and 286 days, and survival of the whole groups 229 and 269 days respectively. Toxicity was worse in the combination arm, with more patients experiencing fatigue, nausea and anorexia, flu-like symptoms and neutropenia. However quality of life was not significantly different in either group, except that fatigue, as measured at week 12 by LASA scales, and activity, as measured by the functional living index, were both improved in the combination.(ABSTRACT TRUNCATED AT 250 WORDS)
在对达卡巴嗪和α-2a干扰素联合用药进行了广泛的II期试验之后，我们开展了一项前瞻性、随机、对照试验，比较该联合用药与单独使用达卡巴嗪作为有症状、可测量的转移性恶性黑色素瘤全身治疗的效果。两个治疗组在年龄、性别、体能状态、无复发生存期、既往治疗及疾病部位方面匹配良好。治疗方案为：联合用药组静脉注射达卡巴嗪，剂量递增，每3周依次为200mg/m²、400mg/m²和800mg/m²；单独用药组每3周静脉注射达卡巴嗪800mg/m²。干扰素皮下注射，第1 - 3天每天3mU，第4 - 70天每天9mU，之后每周3次，每次9mU。除非观察到明显的疾病进展，治疗至少持续6个月。87例患者随机分配至联合用药组，83例患者单独使用达卡巴嗪。缓解率方面，联合用药组完全缓解率为7%，单独用药组为2%；部分缓解率分别为14%和15%，总缓解率分别为21%（95%置信区间13 - 31%）和17%（95%置信区间10 - 27%）。缓解的中位持续时间分别为258天和286天，两组患者的总生存期分别为229天和269天。联合用药组的毒性更严重，更多患者出现疲劳、恶心、厌食、流感样症状和中性粒细胞减少。然而，两组的生活质量无显著差异，不过联合用药组在第12周通过LASA量表测量的疲劳以及通过功能生活指数测量的活动能力均有所改善。（摘要截选至250词）
