Bokemeyer C, Köhrmann O, Tischler J, Weissbach L, Räth U, Haupt A, Schöffski P, Harstrick A, Schmoll H J
Department of Internal Medicine, University of Tübingen, Germany.
Ann Oncol. 1996 Dec;7(10):1015-21. doi: 10.1093/oxfordjournals.annonc.a010493.
Cisplatin-based combination chemotherapy will cure 70% to 80% of patients with metastatic non-seminomatous germ cell tumors but is associated with the possibility of severe neuro-, oto- and nephro-toxicities. Carboplatin, a cisplatin analogue, is an active drug in testicular cancer with a more favourable spectrum of side effects. In a randomized trial, the German Testicular Cancer Study Group compared a combination regimen of carboplatin, etoposide and bleomycin (CEB) to standard cisplatin, etoposide and bleomycin (PEB) chemotherapy for patients with 'minimal-' and moderate-disease' non-seminomatous germ cell tumors, according to the Indiana University classification.
PEB was given for three cycles at standard doses (given days 1-5), and the CEB regimen consisted of carboplatin (target AUC of 5 mg/ml x min) on day 1, etoposide 120 mg/m2 on days 1 to 3 and bleomycin 30 mg on days 1, 8 and 15. Four cycles of CEB were given, with the omission of bleomycin in the fourth cycle. Thus, the cumulative doses of etoposide and bleomycin applied in the two treatment arms were comparable. Fifty-four patients were entered on the trial, 29 were treated with PEB and 25 with CEB chemotherapy. Patients were stratified according to disease extent (minimal versus moderate) and the degree of tumor marker elevation. Thirty-two patients (59%) belonged to the group with minimal disease and low markers.
No significant difference in response to chemotherapy was seen between the two arms, with CR rates of 81% for the PEB arm and 76% for CEB treatment. However, more patients treated with CEB (32% versus 13%) have relapsed after therapy, and 4 patients (16%) have died of disease progression after CEP in contrast to 1 (3%) after PEB therapy. The first interim analysis of negative events (relapse, vital tumor at secondary resection, death from disease and therapy-associated death) showed a significantly higher rate after CEB than after PEB therapy, and the trial was terminated early. After a median follow-up of 33 months for all patients, the calculation of negative events is still significantly in favour of PEB-treated patient, particularly since three late relapses > 2 years have been observed in the CEB arm (P = 0.03).
This randomized trial demonstrates that even with the use of adequate doses of etoposide and full-dose bleomycin, carboplatin cannot altogether replace cisplatin in patients with testicular cancer. Treatment with the PEB regimen remains the standard approach in patients with 'good-risk' non-seminomatous germ cell tumors.
基于顺铂的联合化疗可治愈70%至80%的转移性非精原细胞性生殖细胞肿瘤患者，但存在严重神经毒性、耳毒性和肾毒性的可能性。卡铂是顺铂的类似物，是一种对睾丸癌有效的药物，副作用谱更有利。在一项随机试验中，德国睾丸癌研究组根据印第安纳大学的分类，将卡铂、依托泊苷和博来霉素（CEB）联合方案与标准顺铂、依托泊苷和博来霉素（PEB）化疗方案用于“轻度”和“中度”疾病的非精原细胞性生殖细胞肿瘤患者。
PEB以标准剂量给药三个周期（第1 - 5天给药），CEB方案包括第1天给予卡铂（目标AUC为5mg/ml×min），第1至3天给予依托泊苷120mg/m²，第1、8和15天给予博来霉素30mg。给予四个周期的CEB，第四个周期省略博来霉素。因此，两个治疗组中依托泊苷和博来霉素的累积剂量相当。54例患者进入试验，29例接受PEB治疗，25例接受CEB化疗。患者根据疾病范围（轻度与中度）和肿瘤标志物升高程度进行分层。32例患者（59%）属于疾病轻度且标志物水平低的组。
两组化疗反应无显著差异，PEB组的完全缓解率为81%，CEB治疗组为76%。然而，接受CEB治疗的患者中有更多（32%对13%）在治疗后复发，4例患者（16%）在接受CEB治疗后死于疾病进展，而接受PEB治疗后为1例（3%）。对不良事件（复发、二次切除时存在存活肿瘤、死于疾病和治疗相关死亡）的首次中期分析显示，CEB治疗后的发生率显著高于PEB治疗，试验提前终止。所有患者中位随访33个月后，不良事件的计算结果仍明显有利于接受PEB治疗的患者，特别是因为在CEB组观察到3例超过2年的晚期复发（P = 0.03）。
这项随机试验表明，即使使用足够剂量的依托泊苷和全剂量的博来霉素，卡铂在睾丸癌患者中也不能完全替代顺铂。对于“低风险”非精原细胞性生殖细胞肿瘤患者，PEB方案治疗仍然是标准方法。
