Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
Phase II study of 5-fluorouracil (5-FU), leucovorin (LV) and azidodeoxythymidine (AZT) in patients with metastatic colorectal cancer (Meeting abstract).
Proc Annu Meet Am Soc Clin Oncol; 14:A557 1995. Unique Identifier : AIDSLINE ICDB/95613710 Clark JW; Beitz J; Cummings F; Sikov W; Browne M; Akerley W; Wanebo H; Weitberg AB; Kennedy T; Bigley J; Darnowski JD; Brown University Clinical Oncology Group, Providence, RI 02908
Abstract: AZT is a thymidine nucleoside analog presently used in treating HIV infected patients. Although AZT by itself has limited antineoplastic efficacy, experimental studies have demonstrated that the combination of 5-FU and AZT results in significant tumor cell kill as a result of increased incorporation of AZT into cellular nucleic acids. A phase I study using weekly 5-FU doses of 400 mg/m2 defined the maximum tolerated dose of AZT as 7 mg/m2 with the dose limiting toxicity being hypotension. Based on this, a phase II study utilizing this dose of AZT as a 2-hr infusion (given 1 hr after 5-FU) in combination with oral LV (100 mg po hourly for 4 hr prior to 5-FU and at hours 4 and 8 after 5-FU), and bolus 5-FU (400 mg/m2) has been initiated. Each cycle consists of the above therapy given weekly for 4 wk followed by one wk break. Response evaluation is after every 2 cycles. Patients continue on therapy as long as tolerated and there is no progressive disease. Patients may have received prior adjuvant chemotherapy but not chemotherapy for metastatic disease. To date, 23 patients have been accrued of whom 18 are evaluable. There has been 1 complete response and 4 partial responses among 13 patients without prior therapy (38% response rate) whereas none of the 5 patients with prior adjuvant therapy responded. Therapy has been well tolerated with only one grade 3 toxicity (nausea) seen. Mild hypotension occurred in approximately one-half of treatments. This was easily corrected by increasing the rate of normal saline infusion. Accrual and pharmacokinetic studies are ongoing. Based on the encouraging response rate with a low dose of 5-FU, future trials are planned to optimize this dose and incorporate alpha interferon which preclinical studies suggest has synergistic activity with this combination.
Keywords: Antineoplastic Agents, Combined/*TOXICITY/*THERAPEUTIC USE Colorectal Neoplasms/*DRUG THERAPY/PATHOLOGY Drug Administration Schedule Fluorouracil/ADMINISTRATION & DOSAGE Human Hypotension/CHEMICALLY INDUCED Infusions, Intravenous Leucovorin/ADMINISTRATION & DOSAGE Neoplasm Metastasis Neoplasm Staging Zidovudine/ADMINISTRATION & DOSAGE ABSTRACT CLINICAL TRIAL CLINICAL TRIAL, PHASE II 951230
M95C3230
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Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
