Frickhofen N, Berdel W E, Opri F, Haas R, Schneeweiss A, Sandherr M, Kuhn W, Hossfeld D K, Thomssen C, Heimpel H, Kreienberg R, Hinke A, Möbus V
Department of Hematology/Oncology, Universitätsklinikum Ulm, Ulm, Germany.
Bone Marrow Transplant. 2006 Oct;38(7):493-9. doi: 10.1038/sj.bmt.1705472. Epub 2006 Aug 21.
Ovarian cancer is chemosensitive, but most patients with advanced disease die from tumor progression. As 25% of the patients can be cured by chemotherapy, it is reasonable to evaluate high-dose chemotherapy (HDCT). Forty-eight patients with untreated ovarian cancer were entered in a multicenter phase I/II trial of multicycle HDCT. Median age was 46 (19-59 years); International Federation of Gynecology and Obstetrics-stage was III in 79% and IV in 21%; 31% had residual disease >1 cm after surgery. Two courses of induction/mobilization therapy with cyclophosphamide (250 mg/m2) and paclitaxel (250 mg/m2) were used to collect peripheral blood stem cells. HDCT consisted of two courses of carboplatin (area under curve (AUC) 18-22) and paclitaxel followed by one course of carboplatin and melphalan (140 mg/m2) with or without etoposide (1600 mg/m2). Main toxicity was gastrointestinal. Limiting carboplatin to AUC 20 and eliminating etoposide resulted in manageable toxicity (69% without grade 3/4 toxicity). One patient died from treatment-related pneumonitis. At 8 years median follow-up, median progression-free-survival (PFS) and overall survival (OS) is 13.3 and 37.0 months. Five-years PFS and OS is 18 and 33%. Multicycle HDCT is feasible in a multicenter setting. A European phase III trial based on this regimen is evaluating the efficacy of HDCT.
卵巢癌对化疗敏感，但大多数晚期患者死于肿瘤进展。由于25%的患者可通过化疗治愈，因此评估大剂量化疗（HDCT）是合理的。48例未经治疗的卵巢癌患者进入了一项多周期HDCT的多中心I/II期试验。中位年龄为46岁（19 - 59岁）；国际妇产科联盟分期III期占79%，IV期占21%；31%的患者术后残留病灶>1 cm。采用环磷酰胺（250 mg/m²）和紫杉醇（250 mg/m²）进行两个疗程的诱导/动员治疗以采集外周血干细胞。HDCT包括两个疗程的卡铂（曲线下面积（AUC）18 - 22）和紫杉醇，随后是一个疗程的卡铂和美法仑（140 mg/m²），可联合或不联合依托泊苷（1600 mg/m²）。主要毒性为胃肠道毒性。将卡铂限制在AUC 20并去除依托泊苷可使毒性可控（69%无3/4级毒性）。1例患者死于治疗相关的肺炎。中位随访8年时，中位无进展生存期（PFS）和总生存期（OS）分别为13.3个月和37.0个月。5年PFS和OS分别为18%和33%。多周期HDCT在多中心环境中是可行的。基于该方案的一项欧洲III期试验正在评估HDCT的疗效。
