Jelić S, Babovic N, Kovcin V, Milicevic N, Milanovic N, Popov I, Radosavljevic D
Institute for Oncology and Radiology of Serbia, Department of Medical Oncology, Pasterova 14, 11000 Belgrade, Yugoslavia.
Melanoma Res. 2002 Feb;12(1):91-8. doi: 10.1097/00008390-200202000-00013.
The aim of this randomized four-arm phase III study was to evaluate whether there is a difference in activity between regimens containing dacarbazine and regimens without dacarbazine in metastatic melanoma, whether there is a dose-effect relationship for dacarbazine, and whether non-dacarbazine-containing aggressive regimens are in any way superior to non-aggressive ones. A total of 219 patients with metastatic cutaneous melanoma were included in this study; 196 of them were evaluable for activity. The patients were randomized into four treatment arms: arm A (standard dose dacarbazine arm), vincristine 1.4 mg/m2 on day 1, carmustine (BCNU) 60 mg/m2 on day 1, and dacarbazine 300 mg/m2 per 24 h on days 2-5; arm B (high-dose dacarbazine arm), vincristine and BCNU as in arm A and dacarbazine 600 mg/m2 per 24 h on days 2-5; arm C ('aggressive' regimen without dacarbazine), vindesine 3 mg/m2 on day 1, bleomycin 7 mg/m2 per 24 h on days 1-4, and cisplatin 30 mg/m2 per 24 h on days 5-8; arm D ('non-aggressive' regimen without dacarbazine), BCNU 100 mg/m2 on day 1 and procarbazine 90 mg/m2 per 24 h on days 1-10. The four arms were well balanced with regard to patient- and disease-related characteristics. On an intend-to-treat basis, the response rate was 11 out of 49 (22%) in arm A, nine out of 47 (19%) in arm B, 16 out of 63 (25%) in arm C and nine out of 60 (15%) in arm D. There was a large overlap between the 95% confidence intervals and no significant differences in the response rates between the four arms. Median survival in the four treatment arms was 4, 5, 6 and 4 months, respectively, again with no significant differences. Median survival for responders (8, 11, 10 and 13 months, respectively) in all four arms was significantly longer than in non-responders (4, 3, 5 and 4 months, respectively). Arms A, B and C were significantly more toxic compared with arm D, which was for all practical purposes devoid of toxicities. The efficacy of all four regimens thus appeared comparable both in terms of response rate and survival. Responders in all four arms achieved a survival benefit. There does not seem to be a dose-effect relationship for dacarbazine in metastatic melanoma. Chemotherapy from arm D, might be well suited for 'fragile' or elderly patients due to the lack of toxicity.
这项随机四臂III期研究的目的是评估在转移性黑色素瘤中，含达卡巴嗪方案与不含达卡巴嗪方案在活性方面是否存在差异，达卡巴嗪是否存在剂量效应关系，以及不含达卡巴嗪的积极方案是否在任何方面优于非积极方案。本研究共纳入219例转移性皮肤黑色素瘤患者；其中196例可评估活性。患者被随机分为四个治疗组：A组（标准剂量达卡巴嗪组），第1天静脉注射长春新碱1.4mg/m²，第1天静脉注射卡莫司汀（BCNU）60mg/m²，第2 - 5天每24小时静脉注射达卡巴嗪300mg/m²；B组（高剂量达卡巴嗪组），长春新碱和BCNU同A组，第2 - 5天每24小时静脉注射达卡巴嗪600mg/m²；C组（不含达卡巴嗪的“积极”方案组），第1天静脉注射长春地辛3mg/m²，第1 - 4天每24小时静脉注射博来霉素7mg/m²，第5 - 8天每24小时静脉注射顺铂30mg/m²；D组（不含达卡巴嗪的“非积极”方案组），第1天静脉注射BCNU 100mg/m²，第1 - 10天每24小时口服丙卡巴肼90mg/m²。四个治疗组在患者和疾病相关特征方面平衡良好。在意向性分析基础上，A组49例中有11例（22%）有反应，B组47例中有9例（19%）有反应，C组63例中有16例（25%）有反应，D组60例中有9例（15%）有反应。四个组的95%置信区间有很大重叠，反应率无显著差异。四个治疗组的中位生存期分别为4、5、6和4个月，同样无显著差异。所有四个组有反应者的中位生存期（分别为8、11、10和13个月）显著长于无反应者（分别为4、3、5和4个月）。与D组相比，A、B和C组毒性显著更大，而D组实际上没有毒性。因此，所有四种方案在反应率和生存期方面的疗效似乎相当。所有四个组的有反应者均获得了生存益处。在转移性黑色素瘤中，达卡巴嗪似乎不存在剂量效应关系。由于缺乏毒性，D组的化疗可能非常适合“体弱”或老年患者。
