基于人群的伊立替康和卡铂最大耐受剂量。

Wild Carolyn A, Wang Stephen E, Gandara David R, Lara Primo N, Meyers Frederick J, Tanaka Michael, Houston Joan, Lauder Jun, Lau Derick H

University of California, Davis Cancer Center, Veterans Administration, Northern California Health Care System, Sacramento, California, USA.

Oncology (Williston Park). 2003 Jul;17(7 Suppl 7):11-6.

A novel schema of intrapatient dose escalation was applied to determine a population-based maximum tolerated dose (pMTD) for irinotecan (CPT-11, Camptosar) and carboplatin (Paraplatin) in a phase I trial. A total of 74 patients with advanced solid tumors were enrolled with the following characteristics: men/women, 46/28; median age, 61 years; 51 patients with and 23 patients without prior chemotherapy; performance status of 0-1 (93%) and 2 (7%). Patients were started at dose level 1 with irinotecan at 200 mg/m2, and carboplatin at an area under the concentration-time curve (AUC) of 5 mg/mL x min, administered every 21 days. Depending on degree of toxicity observed, the dose for each patient in each subsequent cycle was determined according to a predetermined schema of dose levels. Individual maximum tolerated dose (iMTD) was determined for each patient. The pMTD was defined as the highest dose level for which the incidence of dose-limiting toxicity occurred in less than 33% of the patient population. The most common dose-limiting toxicity included neutropenia (58%), thrombocytopenia (15%), diarrhea (8%), and nausea/emesis (7%). The iMTD ranged from dose level-3 (irinotecan at 100 mg/m2 and carboplatin at an AUC of 4) to dose level 5 (irinotecan at 350 mg/m2 and carboplatin at AUC 6). The pMTD was determined to be dose level-1 and 1 for previously chemotherapy-treated and--untreated patients, respectively. Fifty-nine patients were assessable for response. Of note, a response rate of 40% was observed in 15 patients with relapsed small-cell lung cancer previously treated with platinum-based therapy. We recommend dose level 1 of irinotecan (200 mg/m2) and carboplatin (AUC 5) for chemotherapynaive patients, and dose level-1 of irinotecan (150 mg/m2) and carboplatin (AUC 5) for chemotherapy-treated patients in phase II trials.

在一项I期试验中，采用了一种新的患者体内剂量递增方案来确定基于人群的伊立替康（CPT-11，开普拓）和卡铂（顺铂）的最大耐受剂量（pMTD）。共纳入74例晚期实体瘤患者，其特征如下：男性/女性为46/28；中位年龄61岁；51例患者接受过化疗，23例未接受过化疗；体能状态为0 - 1（93%）和2（7%）。患者从剂量水平1开始，伊立替康剂量为200 mg/m²，卡铂浓度 - 时间曲线下面积（AUC）为5 mg/mL·min，每21天给药一次。根据观察到的毒性程度，每个后续周期中每位患者的剂量根据预定的剂量水平方案确定。为每位患者确定个体最大耐受剂量（iMTD）。pMTD定义为剂量限制毒性发生率在不到33%的患者群体中出现的最高剂量水平。最常见的剂量限制毒性包括中性粒细胞减少（58%）、血小板减少（15%）、腹泻（8%）和恶心/呕吐（7%）。iMTD范围从剂量水平3（伊立替康100 mg/m²和AUC为4的卡铂）到剂量水平5（伊立替康350 mg/m²和AUC为6的卡铂）。对于先前接受过化疗和未接受过化疗的患者，pMTD分别确定为剂量水平1和1。59例患者可评估疗效。值得注意的是，在15例先前接受过铂类治疗的复发性小细胞肺癌患者中观察到40%的缓解率。我们建议在II期试验中，对于未接受过化疗的患者，伊立替康（200 mg/m²）和卡铂（AUC 5）采用剂量水平1，对于接受过化疗的患者，伊立替康（150 mg/m²）和卡铂（AUC 5）采用剂量水平1。