Levi J A, Thomson D, Sandeman T, Tattersall M, Raghavan D, Byrne M, Gill G, Harvey V, Burns I, Snyder R
Royal North Shore Hospital of Sydney, Department of Clinical Oncology, Leonards, NSW, Australia.
J Clin Oncol. 1988 Jul;6(7):1154-60. doi: 10.1200/JCO.1988.6.7.1154.
Two hundred fifty-three patients with advanced germ cell malignancy received initial chemotherapy with cisplatin, vinblastine, and bleomycin followed by surgical resection of residual masses if possible. Patients achieving complete remission (CR) were prospectively randomized to receive 6 months maintenance therapy with vinblastine or no further treatment. CR was achieved in 183 patients (72%) and a further eight patients (4%) had complete resection of residual viable malignancy (no evidence of disease [NED]). Pretreatment factors having a significant adverse influence on response by univariate analysis included extragonadal origin of the tumor, poor performance status, advanced lung or lung and abdominal disease, and elevated serum levels of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) greater than 1,000 ng/mL. Multivariate regression analysis indicated the independent prognostic factors of significance were advanced lung or advanced lung and abdominal disease, total tumor diameter greater than 10 cm, and a serum level of HCG greater than 1,000 ng/mL. Of the toxicities encountered, myelosuppression was significant, being exacerbated by radiotherapy, and seven deaths occurred from septicemia. Bleomycin pulmonary toxicity occurred in 46% of patients and was severe in 4%, resulting in eight deaths. With a median follow-up of 64 months, relapses have occurred in 25 patients with no significant difference between those patients receiving or not receiving maintenance vinblastine. Eight of these relapses occurred beyond 1 year and four beyond 2 years of follow-up. Presently, 68% of the total patient population is alive and disease-free, with 84% of the CR and NED patients alive and 81% alive and disease-free. It is concluded that with prolonged follow-up, vinblastine maintenance therapy does not improve treatment outcome. Moreover, late relapses occur, cautioning against premature pronouncements of cure.
253例晚期生殖细胞恶性肿瘤患者接受了以顺铂、长春碱和博来霉素为主的初始化疗，若可能，随后对残留肿块进行手术切除。达到完全缓解（CR）的患者被前瞻性随机分组，分别接受长春碱6个月的维持治疗或不再接受进一步治疗。183例患者（72%）达到CR，另有8例患者（4%）残留的存活恶性肿瘤被完全切除（无疾病证据[NED]）。单因素分析显示，对反应有显著不利影响的预处理因素包括肿瘤的性腺外起源、较差的体能状态、晚期肺部或肺部及腹部疾病，以及血清人绒毛膜促性腺激素（HCG）和甲胎蛋白（AFP）水平高于1000 ng/mL。多因素回归分析表明，具有显著意义的独立预后因素为晚期肺部或晚期肺部及腹部疾病、肿瘤总直径大于10 cm以及血清HCG水平大于1000 ng/mL。在出现的毒性反应中，骨髓抑制较为显著，放疗会使其加重，7例患者死于败血症。博来霉素肺毒性发生在46%的患者中，4%为严重毒性，导致8例患者死亡。中位随访64个月，25例患者出现复发，接受或未接受长春碱维持治疗的患者之间无显著差异。其中8例复发发生在随访1年后，4例发生在随访2年后。目前，全部患者中有68%存活且无疾病，CR和NED患者中有84%存活，81%存活且无疾病。结论是，随着随访时间延长，长春碱维持治疗并不能改善治疗结果。此外，出现了晚期复发，因此要避免过早宣布治愈。
