ORAL ZIDOVUDINE, CONTINUOUS-INFUSION FLUOROURACIL, AND ORAL LEUCOVORIN CALCIUM - A PHASE-I STUDY

被引:28
作者
POSNER, MR
DARNOWSKI, JW
CALABRESI, P
BRUNETTI, I
CORVESE, D
CURT, G
CUMMINGS, FJ
CLARK, J
BROWNE, MJ
BEITZ, J
WEITBERG, AB
机构
[1] BROWN UNIV, DEPT MED, PROVIDENCE, RI 02912 USA
[2] BROWN UNIV, ROGER WILLIAMS CANC CTR, DIV HEMATOL ONCOL, PROVIDENCE, RI 02912 USA
来源
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 1990年 / 82卷 / 21期
关键词
D O I
10.1093/jnci/82.21.1710
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
A phase I clinical, pharmacologic, and biochemical evaluation of escalating oral zidovudine (AZT) given over 2 days with a fixed dose of continuous-infusion fluorouracil (800 mg/m2 per day × 3 days) and oral leucovorin calcium was performed. Eighteen patients were treated with doses of AZT ranging from 1.0 to 9.0 g/m2 per day. Nausea and vomiting were dose limiting, with a maximally tolerated dose of 7.5 g/m2 per day. Rash and mucositis occurred but were not dose limiting. A dose-related increase in peak plasma levels of AZT was observed, and the alpha half-life of AZT in plasma (75 min) was unaffected by these high doses. At doses above 4.0 g/m2 per day, trough levels significantly increased, perhaps reflecting prolonged absorption from the gut. No responses were observed; however, a significant increase in DNA single-strand breaks was observed in peripheral blood cells after a threshold dose of 4.0 g/m2 per day, confirming a biological effect of AZT in this regimen. Further trials with an intravenous formulation capable of maintaining plasma levels and circumventing dose/limiting toxicity are warranted. [J Natl Cancer Inst 82:1710-1714, 1990] © 1990 Oxford University Press.
引用
收藏
页码:1710 / 1714
页数:5
相关论文
共 19 条
[1]  
BIRNBOIM HC, 1981, CANCER RES, V41, P1889
[2]  
BLEYER WA, 1989, CANCER-AM CANCER SOC, V63, P995
[3]  
BRUNETTI I, 1990, CANCER RES, V50, P4026
[4]  
BRUNETTI I, 1990, P AM ASSOC CANC RES, V31, P2377
[5]  
CALABRESI P, IN PRESS BLOOD
[6]   ENHANCEMENT OF FLUOROURACIL THERAPY BY THE MANIPULATION OF TISSUE URIDINE POOLS [J].
DARNOWSKI, JW ;
HANDSCHUMACHER, RE .
PHARMACOLOGY & THERAPEUTICS, 1989, 41 (1-2) :381-392
[7]  
DARNOWSKI JW, 1990, P AM ASSOC CANC RES, V31, P2361
[8]  
DENTON JE, 1982, CANCER RES, V42, P1176
[9]   ROLE OF CHEMOTHERAPY IN THE TREATMENT OF COLORECTAL-CARCINOMA [J].
KEMENY, N .
SEMINARS IN SURGICAL ONCOLOGY, 1987, 3 (03) :190-214
[10]  
MORAN RG, 1989, CANCER-AM CANCER SOC, V63, P1008, DOI 10.1002/1097-0142(19890315)63:6+<1008::AID-CNCR2820631303>3.0.CO