McClay E F, Goel R, Andrews P, Gorelick S, Kirmani S, Kim S, Braly P, Plaxe S, Hoff S, Alcaraz J
Department of Medicine, University of California, San Diego 92103.
Br J Cancer. 1993 Oct;68(4):783-8. doi: 10.1038/bjc.1993.428.
We attempted to determine the maximum tolerated dose and toxicity of etoposide (VP-16) when administered in combination with carboplatin (CBDCA) (300 mg m-2) and administered via the intraperitoneal (IP) route.
A total of 26 patients were treated on this trial. CBDCA was administered at a fixed dose of 300 mg m-2) while VP-16 was started at a dose of 200 mg m-2 and escalated at 50 mg m-2 increments. Both agents were mixed together in 2 litres of 5% Dextrose and administered as quickly as possible into the peritoneal cavity. Pharmacokinetic studies were performed at the maximum tolerated dose (MTD).
The MTD for this regimen was CBDCA 300 mg m-2 and VP-16 350 mg m-2. Patients > or = 70 years of age or who had received more than six cycles of previous chemotherapy, tolerated this regimen poorly. The MTD for this group of patients was CBDCA 200 mg m-2 and VP-16 50 mg m-2. Neutropenia was the dose limiting toxicity for both groups. The mean peritoneal/plasma peak ratio was 18.3 for CBDCA and 12.7 for VP-16. The pharmacologic advantage (peritoneal/plasma AUC ratio) was 14.9 for CBDCA and 8.8 for VP-16. Although measurable disease was not a requirement for entrance into this study a response rate of 27% was noted in 15 patients with evaluable disease who had ovarian cancer.
A pharmacologic advantage exists for both CBDCA and VP-16 when administered together via the IP route.
我们试图确定依托泊苷（VP - 16）与卡铂（CBDCA）（300 mg/m²）联合经腹腔（IP）途径给药时的最大耐受剂量和毒性。
本试验共治疗26例患者。卡铂以固定剂量300 mg/m²给药，而依托泊苷起始剂量为200 mg/m²，并以50 mg/m²的增量递增。两种药物在2升5%葡萄糖中混合，尽快注入腹腔。在最大耐受剂量（MTD）下进行药代动力学研究。
该方案的MTD为卡铂300 mg/m²和依托泊苷350 mg/m²。年龄≥70岁或之前接受过六个以上周期化疗的患者对该方案耐受性较差。这组患者的MTD为卡铂200 mg/m²和依托泊苷50 mg/m²。中性粒细胞减少是两组的剂量限制性毒性。卡铂的平均腹膜/血浆峰浓度比为18.3，依托泊苷为12.7。药物优势（腹膜/血浆AUC比）卡铂为14.9，依托泊苷为8.8。尽管本研究入组不要求有可测量的疾病，但在15例可评估疾病的卵巢癌患者中观察到27%的缓解率。
卡铂和依托泊苷经腹腔联合给药时均具有药物优势。
