Motzer R J, Mazumdar M, Bajorin D F, Bosl G J, Lyn P, Vlamis V
Department of Medicine, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, New York, NY, USA.
J Clin Oncol. 1997 Jul;15(7):2546-52. doi: 10.1200/JCO.1997.15.7.2546.
A treatment program that included high-dose carboplatin, etoposide, and cyclophosphamide (CEC) followed by autologous bone marrow transplantation (AuBMT) was investigated as first-line therapy in patients with poor-risk germ cell tumors (GCTs).
Previously untreated GCT patients with poor-risk features were treated with etoposide, ifosfamide, and cisplatin (VIP) with or without high-dose CEC plus AuBMT. Patients qualified for a change to high-dose CEC if a prolonged clearance of elevated serum tumor markers was observed after two cycles of the cisplatin-containing regimen.
Sixteen patients were treated with VIP alone and 14 with VIP and high-dose CEC. Seventeen patients (57%) achieved a complete response. Twenty are alive (67%) and 15 (50%) are free of disease at a median follow-up time of 30 months. For 23 cycles of high-dose CEC, the median time from AuBMT to a granulocyte count > or = 0.5/microL was 11 days (range, 0 to 14) and to a platelet count 50,000/microL, 19 days (range, 14 to 34). The survival of 58 patients treated in two of our center's programs that incorporated high-dose chemotherapy (high-dose carboplatin plus etoposide [CE] and CEC) was compared with our prior experience with conventional-dose cisplatin chemotherapy alone in poor-risk GCT. Patients treated with marker-dependent, early-intervention high-dose chemotherapy experienced longer survival (P = .001).
In this setting, high-dose CEC was well tolerated, cumulative toxicity was lacking, and the recovery of blood counts after AuBMT was rapid. A randomized trial has been initiated to investigate further the role of high-dose CEC in first-line therapy for patients with poor-risk GCT.
研究一种治疗方案,即采用大剂量卡铂、依托泊苷和环磷酰胺(CEC),随后进行自体骨髓移植(AuBMT),作为高危生殖细胞肿瘤(GCT)患者的一线治疗方法。
既往未接受治疗且具有高危特征的GCT患者接受依托泊苷、异环磷酰胺和顺铂(VIP)治疗,可联合或不联合大剂量CEC及AuBMT。如果在含顺铂方案的两个周期后观察到血清肿瘤标志物升高的清除时间延长,则符合条件的患者可改为大剂量CEC治疗。
16例患者仅接受VIP治疗,14例患者接受VIP和大剂量CEC治疗。17例患者(57%)达到完全缓解。中位随访时间为30个月时,20例患者存活(67%),15例患者(50%)无疾病。对于23个周期的大剂量CEC治疗,从AuBMT到粒细胞计数≥0.5/μL的中位时间为11天(范围0至14天),到血小板计数≥50,000/μL的中位时间为19天(范围14至34天)。将我们中心两个采用大剂量化疗方案(大剂量卡铂加依托泊苷[CE]和CEC)治疗的58例患者的生存情况与我们既往单纯使用常规剂量顺铂化疗治疗高危GCT的经验进行了比较。接受基于标志物的早期干预大剂量化疗的患者生存时间更长(P = 0.001)。
在这种情况下,大剂量CEC耐受性良好,无累积毒性,AuBMT后血细胞计数恢复迅速。已启动一项随机试验,以进一步研究大剂量CEC在高危GCT患者一线治疗中的作用。