Clark P I, Cottier B
Mersey Regional Centre for Radiotherapy and Oncology, Clatterbridge Hospital, Wirral, Merseyside, UK.
Semin Oncol. 1992 Dec;19(6 Suppl 14):36-9.
Pharmacologic studies in patients with small cell lung cancer treated with differing schedules of intravenous etoposide over 1 to 8 days have suggested that etoposide's antitumor cytotoxicity is related to duration of exposure to low plasma levels of drug. Three phase II studies have been performed in 78 patients with extensive small cell lung cancer examining the efficacy and toxicity of 50-mg doses of oral etoposide given twice daily for 14 days every 3 weeks, once daily for 21 days every 4 weeks, and twice daily for 10 days every 3 weeks. Partial response rates were observed in 76%, 52%, and 70% of patients, respectively. Median response duration appeared similar in all three schedules, but the time to achieve a response appeared longer in the 21-day, once-daily schedule. Bone marrow toxicity was generally mild, but occasionally severe nadir blood counts were observed. These studies demonstrate that prolonged administration of low-dose oral etoposide is very active in small cell lung cancer, and that a twice-daily regimen is preferable in view of the greater rapidity of response and possibly higher response rate. The optimal duration of a twice-daily, 50-mg dosage schedule remains to be determined.
对小细胞肺癌患者进行的药理学研究表明，依托泊苷的抗肿瘤细胞毒性与低血浆药物水平暴露持续时间有关。在这些研究中，患者接受了不同给药方案，静脉注射依托泊苷，持续1至8天。三项II期研究纳入了78例广泛期小细胞肺癌患者，研究了每3周口服依托泊苷50毫克、每日两次、共14天，每4周口服依托泊苷50毫克、每日一次、共21天，以及每3周口服依托泊苷50毫克、每日两次、共10天的疗效和毒性。部分缓解率分别为76%、52%和70%。在所有三种给药方案中，中位缓解持续时间似乎相似，但在每日一次、持续21天的给药方案中，达到缓解的时间似乎更长。骨髓毒性一般较轻，但偶尔会观察到严重的最低点血细胞计数。这些研究表明，小剂量口服依托泊苷的长期给药在小细胞肺癌中非常有效，鉴于缓解速度更快且可能缓解率更高，每日两次的给药方案更可取。每日两次、50毫克给药方案的最佳持续时间仍有待确定。
