Randomized phase II study of weekly paclitaxel versus paclitaxel and carboplatin as second-line therapy in disseminated melanoma: a multicentre trial of the Dermatologic Co-operative Oncology Group (DeCOG)
Randomized phase II study of weekly paclitaxel versus paclitaxel and carboplatin as second-line therapy in disseminated melanoma: a multicentre trial of the Dermatologic Co-operative Oncology Group (DeCOG)
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DOI：
10.1097/00008390-200310000-00012
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发表时间：
2003-10-01
影响因子：
2.2
通讯作者：
Schadendorf, D
中科院分区：
文献类型：
--
作者：
Zimpfer-Rechner, C;Hofmann, U;Schadendorf, D
IV期黑色素瘤预后差，从诊断为远处转移起的中位生存时间为3至11个月。一线治疗方案的缓解率约为20%。到目前为止，还没有建立二线治疗。我们进行了一项随机、多中心、二线II期临床研究，研究紫杉醇单药治疗或与卡铂联合治疗门诊患者。在A组中，紫杉醇以100 mg/m2的剂量静脉内给药，每周第1天，持续6周。在B组中，紫杉醇以80 mg/m2的剂量静脉给药，然后卡铂200 mg/m2，每周第1天，持续6周。下一个周期在2周间歇后给药。评估两组的缓解率、生存时间、至进展时间和毒性。研究在40例患者后停止，因为两组的总体应答率均低于10%。仅接受紫杉醇治疗的患者开始二线治疗后的中位生存时间为209天（+/- 196天），接受紫杉醇/卡铂治疗的患者为218天。两组的中位至进展时间约为56天。16周后观察到两次部分缓解，分别持续8周和12周。虽然这两种治疗方式耐受性良好，血液学毒性较高的组合arm. This是迄今为止最大的二线临床II期研究报告的黑色素瘤。然而，紫杉醇与或不与卡铂只有有限的疗效，这些药物的组合显着增加血液学毒性，而不提高反应或生存率。
Stage melanoma IV has a poor prognosis, with a median survival time between 3 and 11 months from the diagnosis of distant metastases. Response rates in first-line regimens are around 20%. To date, no second-line treatment has been established. We performed a randomized, multicentre, second-line clinical phase II study of paclitaxel either as monotherapy or combined with carboplatin given on an outpatient basis. In arm A, paclitaxel was administered at a dose of 100 mg/m(2) intravenously on day 1 each week for 6 weeks. In arm B, paclitaxel was administered at a dose of 80 mg/m(2) intravenously followed by carboplatin 200 mg/m(2) on day 1 each week for 6 weeks. The next cycle was administered after a 2 week intermission. The response rate, survival time, time-to-progression and toxicity were assessed in both arms. The study was stopped after 40 patients because the overall response rate was below 10% in both arms. The median survival time after initiation of second-line treatment was 209 days (+/- 196 days) for patients treated with paclitaxel only, and 218 days for those treated with paclitaxel/carboplatin. The median time-to-progression was around 56 days in both arms. Two partial responses were observed after 16 weeks, lasting for 8 and 12 weeks, respectively. Although both treatment modalities were well tolerated, haematological toxicity was higher in the combination arm. This is so far the largest second-line clinical phase II study reported in melanoma. However, paclitaxel with or without carboplatin had only limited efficacy, and the combination of these drugs adds significantly to haematological toxicity without improving response or survival rates.