Krook J E, Jett J R, Little C
Duluth Clinic CCOP, MN 55805.
Am J Clin Oncol. 1989 Apr;12(2):114-7. doi: 10.1097/00000421-198904000-00005.
Although the etoposide (VP-16) and cisplatin combination has shown therapeutic activity in lung cancer, human results to date have not matched the expectation of synergism raised by animal model studies. Laboratory studies suggest that therapeutic synergism of etoposide and cisplatin may be related to factors of drug concentration, time of exposure, and sequencing. To pursue this question, we developed regimens of etoposide given by 72 h infusion in conjunction with sequential bolus or infusion cisplatin. Thirty-two patients were entered. Fourteen of 15 small-cell lung cancer patients had a response (CR, PR, regression) with a median survival of 321 days. Nine of 17 patients with non-small-cell lung cancer achieved a response, including two CRs. The median survival is 201 days. The major toxicity was myelosuppression. At the highest etoposide dosage tested, 42% of patients had leukopenia less than 2000/mm3. There were no treatment-related deaths. This new approach of combined etoposide and cisplatin therapy shows promising therapeutic activity against both small cell and non-small-cell lung cancer.
尽管依托泊苷（VP - 16）和顺铂联合用药已在肺癌治疗中显示出活性，但迄今为止的人体研究结果尚未达到动物模型研究中所预期的协同作用效果。实验室研究表明，依托泊苷和顺铂的治疗协同作用可能与药物浓度、暴露时间及给药顺序等因素有关。为探讨这一问题，我们制定了依托泊苷持续输注72小时并联合顺铂静脉推注或持续输注的治疗方案。共纳入32例患者。15例小细胞肺癌患者中有14例有反应（完全缓解、部分缓解、病情稳定），中位生存期为321天。17例非小细胞肺癌患者中有9例有反应，包括2例完全缓解。中位生存期为201天。主要毒性为骨髓抑制。在测试的最高依托泊苷剂量下，42%的患者白细胞减少至低于2000/mm³。无治疗相关死亡。这种依托泊苷和顺铂联合治疗的新方法对小细胞肺癌和非小细胞肺癌均显示出有前景的治疗活性。
