Möbus Volker, Wandt Hannes, Frickhofen Norbert, Bengala Carmelo, Champion Kim, Kimmig Rainer, Ostermann Helmut, Hinke Axel, Ledermann Jonathan A
Department of Obstetrics and Gynecology, Städtisches Klinikum, Gotenstrasse 6-8, D-65929 Frankfurt, Germany.
J Clin Oncol. 2007 Sep 20;25(27):4187-93. doi: 10.1200/JCO.2006.09.7527. Epub 2007 Aug 13.
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.
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%.
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).
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.
尽管卵巢癌是对化疗最敏感的实体瘤之一，但根治性手术和化疗后治愈的情况并不常见。开展了一项随机试验，比较高剂量序贯化疗联合外周血干细胞（PBSC）支持与铂类联合化疗，以研究剂量强化是否能改善预后。
149例未经治疗的卵巢癌患者在肿瘤减灭术后被随机分配，接受标准联合化疗或序贯高剂量（HD）治疗，即先进行两个周期的环磷酰胺和紫杉醇治疗，随后进行三个周期的HD卡铂和紫杉醇治疗，并给予PBSC支持。最后一个周期添加了HD美法仑。中位年龄为50岁（范围20至65岁），国际妇产科联盟分期为IIb/IIc期的占4%，III期占78%，IV期占17%。
HD组76%的患者接受了全部五个周期的治疗，主要毒性反应为神经/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，标准组的无进展生存期为20.5个月，HD组为29.6个月（风险比[HR]，0.84；95%可信区间[CI]，0.56至1.26；P，0.40）。标准组的中位总生存期（OS）为62.8个月，HD组为54.4个月（HR，1.17；95%CI，0.71至1.94；P，0.54）。
这是第一项比较序贯HD化疗与标准剂量化疗用于晚期卵巢癌患者一线治疗的随机试验。我们观察到无进展生存期或OS无统计学显著差异，并得出结论，HD化疗似乎并不优于传统剂量化疗。
