title: Phase I trial of high-dose infused zidovudine combined with leucovorin plus fluorouracil.
abstract: This phase I trial evaluated a high-dose, short-term infusion of zidovudine (AZT) following oral leucovorin (LV) and bolus 5-fluorouracil (FUra). Thirteen patients with metastatic cancer received 30 cycles of therapy. Plasma monitoring demonstrated a dose-dependent increase in peak plasma levels of AZT through the range of dose levels, from 104.3 +/- 8.7 microM at the 1.5 g/m2 dose of AZT to 1312.6 +/- 165.9 microM at the 11.0 g/m2 dose. While AZT did not potentiate the usual clinical toxicities of LV plus FUra, an unexpected finding of symptomatic hypotension during the AZT infusion was the dose-limiting toxicity in this trial. One partial response was observed in a previously untreated patient with metastatic colorectal cancer. The maximal tolerated dose of AZT, 7.0 g/m2 over 2 hr, is recommended for future phase II evaluation of this novel combination.
authors.affiliation: Department of Medicine, Roger Williams Hospital, Providence, Rhode Island, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Beitz
authors.forename: J W
authors.initials: JW
authors.lastname: Damowski
authors.forename: F J
authors.initials: FJ
authors.lastname: Cummings
authors.forename: M J
authors.initials: MJ
authors.lastname: Browne
authors.forename: J W
authors.initials: JW
authors.lastname: Clark
authors.forename: J W
authors.initials: JW
authors.lastname: Bigley
authors.forename: A B
authors.initials: AB
authors.lastname: Weitberg
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D015215:Zidovudine / Q000008:administration & dosage / Q000097:blood
chemical_list: D015215:Zidovudine; D002955:Leucovorin; D005472:Fluorouracil