Hainsworth J D, Johnson D H, Frazier S R, Greco F A
Division of Oncology, Vanderbilt University Medical Center, Nashville, TN 37232.
J Clin Oncol. 1989 Mar;7(3):396-401. doi: 10.1200/JCO.1989.7.3.396.
In this phase I study, we administered etoposide (VP-16) orally for 21 consecutive days to patients with advanced refractory cancers. All patients had received previous chemotherapy, and 50% of patients had received more than one combination regimen. When given for 21 consecutive days, the maximum-tolerated dose of oral VP-16 was 50 mg/m2/d. Myelosuppression was the dose-limiting toxicity, and occurred between days 21 and 28. In most patients, blood counts had recovered sufficiently by day 35 to begin another 3-week course. WBC count nadirs of less than 1,000/microL occurred in four of 20 courses at this dose, and three patients required hospitalization for treatment of neutropenia and fever. Alopecia occurred in most patients; gastrointestinal (GI) and other toxicities were uncommon. Five of 16 patients with measurable tumor had partial responses of 3 to 4 months duration. Four of these five patients had malignancies that are usually unresponsive to VP-16 when administered by previously investigated schedules. This method of VP-16 administration is well tolerated, convenient, and may optimize antitumor efficacy by exploiting the schedule dependency of this drug. Phase II studies are necessary to define the level of activity of this schedule of VP-16.
在这项I期研究中，我们对晚期难治性癌症患者连续21天口服依托泊苷（VP - 16）。所有患者此前均接受过化疗，50%的患者接受过不止一种联合化疗方案。连续给药21天时，口服VP - 16的最大耐受剂量为50mg/m²/天。骨髓抑制是剂量限制性毒性，发生在第21天至28天之间。在大多数患者中，到第35天时血细胞计数已充分恢复，可开始另一个为期3周的疗程。在此剂量下，20个疗程中有4个疗程的白细胞计数最低点低于1000/微升，3名患者因中性粒细胞减少和发热需要住院治疗。大多数患者出现脱发；胃肠道（GI）和其他毒性反应不常见。16例可测量肿瘤的患者中有5例出现了持续3至4个月的部分缓解。这5例患者中有4例所患恶性肿瘤按先前研究的给药方案使用VP - 16时通常无反应。这种VP - 16给药方法耐受性良好、方便，并且通过利用该药物的给药方案依赖性可能优化抗肿瘤疗效。有必要进行II期研究以确定这种VP - 16给药方案的活性水平。
