Phase III trial of high-dose sequential chemotherapy with peripheral blood stem cell support compared with standard dose chemotherapy for first-line treatment of advanced ovarian cancer:: Intergroup trial of the AGO-Ovar/AIO and EBMT
Phase III trial of high-dose sequential chemotherapy with peripheral blood stem cell support compared with standard dose chemotherapy for first-line treatment of advanced ovarian cancer:: Intergroup trial of the AGO-Ovar/AIO and EBMT
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DOI：
10.1200/jco.2006.09.7527
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发表时间：
2007-09-20
影响因子：
45.3
通讯作者：
Ledermann, Jonathan A.
中科院分区：
文献类型：
--
作者：
Moebus, Volker;Wandt, Hannes;Ledermann, Jonathan A.
目的卵巢癌是对化疗最敏感的实体肿瘤之一，但根治性手术和化疗后治愈的情况并不常见。为探讨大剂量序贯化疗加外周血干细胞支持与以铂为基础的联合化疗是否能改善疗效，对149例初治卵巢癌患者随机分为两组，分别接受标准联合化疗或环磷酰胺+紫杉醇序贯大剂量化疗，后加用卡铂、紫杉醇+外周血干细胞支持。在最后一个周期中加入了HD马法兰。中位年龄50岁(20~65岁)，国际妇产科联合会IIb/IIc期4%，III期78%，IV期17%。结果76%的患者接受HD治疗，主要不良反应为神经/耳毒性、胃肠道毒性和感染，1例死于失血性休克。中位随访38个月后，标准组和HD组的无进展生存期分别为20.5个月和29.6个月(风险比[HR]，0.84；95%CI，0.56至1.26；P，0.40)。中位总生存期(OS)标准组为62.8个月，HD组为54.4个月(HR，1.17；95%CI，0.71~1.94；P，.54)。结论这是首个比较序贯HD和标准剂量化疗一线治疗晚期卵巢癌的随机试验。我们在无进展生存率或OS方面没有观察到统计学上的显著差异，并得出结论，HD化疗似乎并不优于常规剂量的化疗。
Purpose Although ovarian cancer is one of the most chemotherapy-sensitive solid tumors, cure after radical surgery and chemotherapy is uncommon. A randomized trial comparing high-dose sequential chemotherapy with peripheral blood stem cell (PBSC) support with platinum-based combination chemotherapy was conducted to investigate whether dose-intensification improves outcome.Patients and Methods One hundred forty-nine patients with untreated ovarian cancer were randomly assigned after debulking surgery to receive standard combination chemotherapy or sequential high-dose (HD) treatment with two cycles of cyclophosphamide and paclitaxel followed by three cycles of HD carboplatin and paclitaxel with PBSC support. HD melphalan was added to the final cycle. The median age was 50 years (range, 20 to 65 years) and International Federation of Gynecology and Obstetrics stage was IIb/IIc in 4%, III in 78%, and IV in 17%.Results Seventy-six percent of patients received all five cycles in the HD arm and the main toxicities were neuro-/ototoxicity, gastrointestinal toxicity, and infection and one death from hemorrhagic shock. After a median follow-up of 38 months, the progression-free survival was 20.5 months in the standard arm and 29.6 months in the HD arm (hazard ratio [HR], 0.84; 95% CI, 0.56 to 1.26; P,.40). Median overall survival (OS) was 62.8 months in the standard arm and 54.4 months in the HD arm (HR, 1.17; 95% CI, 0.71 to 1.94; P,.54).Conclusion This is the first randomized trial comparing sequential HD versus standard dose chemotherapy in first-line treatment of patients with advanced ovarian cancer. We observed no statistically significant difference in progression-free survival or OS and conclude that HD chemotherapy does not appear to be superior to conventional dose chemotherapy.