Splinter T, Kok T, Kho S, Lameris H, ten Kate F, Dalesio O, Dolman B, Palmen F, Bouvy J, Burghouts J
Semin Oncol. 1986 Sep;13(3 Suppl 3):97-103.
Sixty patients with inoperable non-small-cell lung cancer (NSCLC) were entered into a phase II study that tested the combination of cisplatin (80 mg/m2, day, etoposide intravenously (IV) (100 mg, days 1 and etoposide orally (200 mg/m2, days 3 and 5). The regimen was repeated every 28 days for six courses, after which patients were allowed to receive additional treatment at the discretion of their physician. Overall objective response rate in 51 evaluable patients was 69% (95% confidence interval: range, 56% to 81%), with 16% sustaining complete remission (CR), 53% partial remission (PR), 17% stable disease (SD), and 14% progressive disease (PD). CR was pathologically confirmed by bronchoscopy and biopsy. One patient with a clinical PR underwent surgery and was shown to have a pathologic CR. Median survival of all evaluable patients was 52 weeks, greater than 75 weeks for CR patients, 52 weeks for PR patients, 42 weeks for SD patients, and 13 weeks for PD patients. Eleven patients (21.5%) developed CNS metastases, which resulted in the deaths of ten. Survival was significantly correlated with extent of disease, performance status, and albumin level, but not with histology or weight loss. Tumor response was significantly correlated only with histology (squamous-cell and large-cell undifferentiated carcinoma greater than adenocarcinoma). Side effects were nausea, vomiting, anorexia, alopecia, bone marrow suppression, and nephrotoxicity. One patient died from leukopenia and sepsis. Pharmacokinetic studies in ten patients showed the continuous presence of etoposide in plasma for six days at a level of at least 220 to 480 ng/mL. In order to investigate whether this very effective combination of cisplatin and etoposide can prolong survival in NSCLC, it will be tested as preoperative chemotherapy in a randomized trial in operable patients with T1N1 and T2N0-1 disease.
60例无法手术的非小细胞肺癌（NSCLC）患者进入一项II期研究，该研究测试了顺铂（80mg/m²，第1天静脉注射）与依托泊苷联合用药方案，其中依托泊苷静脉注射（100mg，第1天），口服（200mg/m²，第3天和第5天）。该方案每28天重复一次，共六个疗程，之后患者可由医生酌情决定接受额外治疗。51例可评估患者的总体客观缓解率为69%（95%置信区间：范围为56%至81%），其中16%持续完全缓解（CR），53%部分缓解（PR），17%疾病稳定（SD），14%疾病进展（PD）。CR经支气管镜检查和活检病理证实。1例临床PR患者接受手术，病理显示为CR。所有可评估患者的中位生存期为52周，CR患者大于75周，PR患者52周，SD患者42周，PD患者13周。11例患者（21.5%）发生中枢神经系统转移，其中10例死亡。生存期与疾病范围、体能状态和白蛋白水平显著相关，但与组织学类型或体重减轻无关。肿瘤反应仅与组织学类型显著相关（鳞状细胞癌和大细胞未分化癌的反应大于腺癌）。副作用包括恶心、呕吐、厌食、脱发、骨髓抑制和肾毒性。1例患者死于白细胞减少和败血症。对10例患者的药代动力学研究表明，依托泊苷在血浆中持续存在6天，水平至少为220至480ng/mL。为了研究顺铂和依托泊苷这种非常有效的联合用药方案是否能延长NSCLC患者的生存期，将在一项针对T1N1和T2N0-1期可手术患者的随机试验中作为术前化疗进行测试。
