Phase II study of 5-fluoruracil leucovorin and azidothymidine in patients with metastatic colorectal cancer

摘要: The primary objective of this study was to determine the response rate patients with metastatic colorectal cancer combined therapy 5-fluorouracil (5-FU), leucovorin, and intravenous azidothymidine (AZT), a thymidine nucleoside analog. By itself, AZT has limited antineoplastic efficacy. However, experimental studies indicate that 5-FU enhances antitumor activity by inhibiting synthesis normal nucleotides which competes for incorporation into nucleic acids. A phase I defined maximum tolerated dose as 7 g/m2 hypotension during infusion being dose-limiting toxicity. II performed oral leucovorin (100 mg p.o. hourly 4 h prior 8 after 5-FU), bolus (400 mg/m2) followed 1 later 2-h (7 g/m2). Treatment given weekly weeks 1-week break, constituted cycle therapy. Responses were evaluated every two cycles. Patients continued on long they treatment did not have progressive disease. Of 15 evaluable who had received no chemotherapy there complete partial responses (a 33% rate), whereas only 6 adjuvant (17%). An additional 10 stable disease lasting 2–14 months. Therapy well one instance each grade 3 nausea vomiting, diarrhea, anemia, hypotension. Approximately 50% treatments accompanied mild hypotension, easily corrected increasing saline infusion. There difficulty administering regimen in outpatient setting. While overall (29%) is comparable seen combinations alone, most reported series considerably higher utilized than study. Since present experienced relatively little toxicity, would appear be feasible might result rate.