WR-2721与卡铂的I期研究。

Phase I study of WR-2721 and carboplatin.

作者信息

Budd G T, Ganapathi R, Bauer L, Murthy S, Adelstein D, Weick J, Gibson V, McLain D, Sergi J, Bukowski R M

机构信息

Department of Hematology/Medical Oncology, Cleveland Clinic, Ohio 44195.

出版信息

Eur J Cancer. 1993;29A(8):1122-7. doi: 10.1016/s0959-8049(05)80301-6.

DOI:10.1016/s0959-8049(05)80301-6

PMID:8390844

Abstract

Because WR-2721 reduces the toxicity of cisplatin and carboplatin in preclinical systems, we have treated 35 patients in a phase I study of WR-2721 and carboplatin. As the plasma half-life of WR-2721 is short relative to that of carboplatin, WR-2721 was administered in two divided doses. This schedule produced acceptable toxicity in 24 patients treated with carboplatin 400 mg/m2 and escalating doses of WR-2721. In the subsequent 11 patients, WR-2721 was fixed at 740 mg/m2/dose and the dose of carboplatin was escalated. With WR-2721, grade 3-4 thrombopenia (platelets < 50 x 10(9)/l) was produced in 4/5 patients treated with carboplatin 625 mg/m2 and in 1/6 patients treated with carboplatin 500 mg/m2. Carboplatin pharmacokinetic parameters in 4 patients were similar to those reported for carboplatin alone. These results suggest that WR-2721 might increase the maximum tolerated dose of carboplatin from 400 to 500 mg/m2.

摘要

由于WR-2721在临床前系统中可降低顺铂和卡铂的毒性，我们在一项WR-2721与卡铂的I期研究中对35例患者进行了治疗。鉴于WR-2721的血浆半衰期相对于卡铂较短，故将WR-2721分两次给药。该给药方案在24例接受400mg/m²卡铂及递增剂量WR-2721治疗的患者中产生了可接受的毒性。在随后的11例患者中，WR-2721固定为740mg/m²/剂量，卡铂剂量递增。使用WR-2721时，接受625mg/m²卡铂治疗的5例患者中有4例出现3-4级血小板减少（血小板<50×10⁹/L），接受500mg/m²卡铂治疗的6例患者中有1例出现该情况。4例患者的卡铂药代动力学参数与单独使用卡铂时报道的参数相似。这些结果表明，WR-2721可能会将卡铂的最大耐受剂量从400mg/m²提高到500mg/m²。