Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: A gynecologic oncology group study
Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: A gynecologic oncology group study
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DOI：
10.1200/jco.2004.07.184
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发表时间：
2004-06-01
影响因子：
45.3
通讯作者：
Burks, RT
中科院分区：
文献类型：
--
作者：
Fleming, GF;Brurietto, VL;Burks, RT
目的.为了确定紫杉醇加阿霉素加顺铂是否改善晚期或复发性子宫内膜癌妇女的总生存期（OS），次要比较包括无进展生存期（PFS），反应率（RR）和毒性。合格的、同意的患者接受多柔比星60 mg/m2+顺铂50 mg/m2（AP），或多柔比星45 mg/m2+顺铂50 mg/m2（第1天），随后接受紫杉醇160 mg/m2（第2天）+非格司亭支持（TAP）。在既往接受过盆腔放疗和年龄大于65岁的患者中，AP组的初始阿霉素剂量降至45 mg/m2。两种方案每3周重复一次，最多7个周期。患者在每个周期前完成神经毒性问卷。有273名妇女（10名不合格）登记。TAP组的客观缓解率（57%对34%，P <0.01）、PFS（中位数，8.3对5.3个月; P <0.01）和OS（中位数，15.3对12.3个月; P = 0.037）均有所改善。治疗在血液学上耐受性良好，只有2%的患者接受AP，3%的患者接受TAP经历贫血发热。接受TAP的患者神经毒性更严重，3级周围神经病变为12%，2级周围神经病变为27%，而接受AP的患者分别为1%和4%。两个周期治疗后，TAP组患者报告的神经毒性显著较高。与AP相比，TAP显著改善RR、PFS和OS。在高风险的辅助治疗环境中评价该方案是必要的，但应密切关注周围神经病变风险的增加。(C)2004年，美国临床肿瘤学会。
Purpose. To determine whether the addition of paclitaxel to doxorubicin plus cisplatin improves overall survival (OS) in women with advanced or recurrent endometrial carcinoma, Secondary comparisons included progression-free survival (PFS), response rate (RR), and toxicities.Patients and Methods. Eligible, consenting patients received doxorubicin 60 mg/m(2) and cisplatin 50 mg/m(2) (AP), or doxorubicin 45 mg/m(2) and cisplatin 50 mg/m(2) (day 1), followed by paclitaxel 160 mg/m(2) (day 2) with filgrastim support (TAP). The initial doxorubicin dose in the AP arm was reduced to 45 mg/m(2) in patients with prior pelvic radiotherapy and those older than 65 years. Both regimens were repeated every 3 weeks to a maximum of seven cycles. Patients completed a neurotoxicity questionnaire before each cycle.Results. Two hundred seventy-three women (10 ineligible) were registered. Objective response (57% v 34%, P < .01), PFS (median, 8.3 v 5.3 months; P < .01), and OS (median, 15.3 v 12.3 months; P = .037) were improved with TAP. Treatment was hematologically well tolerated, with only 2% of patients receiving AP, and 3% of patients receiving TAP experiencing neutropenic fever. Neurologic toxicity was worse for those receiving TAP, with 12% grade 3, and 27% grade 2 peripheral neuropathy, compared with 1 % and 4%, respectively, in those receiving AP. Patient-reported neurotoxicity was significantly higher in the TAP arm following two cycles of therapy.Conclusion. TAP significantly improves RR PFS, and OS compared with AP. Evaluation of this regimen in the high-risk adjuvant setting is warranted, but close attention should be paid to the increased risk of peripheral neuropathy. (C) 2004 by American Society of Clinical Oncology.