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Phase I evaluation of therapy with four schedules of 5-fluorouracil by continuous infusion combined with recombinant interferon alpha.
Clin Cancer Res. 1995 Jun; 1(6):615-20.CC

Abstract

The purpose of this study was to determine the maximum tolerated dose and dose-limiting toxicities of 5-fluorouracil (5-FU) when administered concurrently with recombinant IFN-alpha using four continuous infusion (CI) dosing schedules of 5-FU. Forty-five patients with advanced or refractory cancers were treated with 5-FU by CI, plus IFN during the infusion only, by one of four schedules: schedule A: 24-h 5-FU infusion repeated weekly, 9 x 10(6) units IFN x 2 doses weekly; schedule B: 48-h 5-FU infusion repeated weekly, 9 x 10(6) units IFN x 4 doses weekly; schedule C: 5-day 5-FU infusion repeated every 3 weeks, 9 x 10(6) units IFN three times weekly; and schedule D: 21-day 5-FU infusion, repeated after 7 days off therapy, 9 x 10(6) units IFN three times weekly. At least three patients were treated at all dose levels. Doses of 5-FU were escalated to the next level if less than one half of the patients at a given level developed grades 2-4 toxicity. The maximum tolerated dose for 5-FU was 2150 mg/m2/week for schedule A (24-h CI), 2350 mg/m2/week for schedule B (48-h CI), 750 mg/m2/day for schedule C (5-day CI), and 175 mg/m2/day for schedule D (21-day CI). Median delivered dose intensities at these levels were 1788 mg/m2/week for schedule A, 2192 mg/m2/week for schedule B, 1250 mg/m2/week for schedule C, and 593 mg/m2/week for schedule D. The dose-limiting toxicities were hematological and gastrointestinal (stomatitis, diarrhea, nausea, anorexia) for schedules A and B and gastrointestinal (mostly stomatitis) for schedules C and D. Severe fatigue due to IFN was rare. Responses correlated with toxicity >/= grade 2, but not with increased dose intensity. Responses were noted in several tumor types on schedules A, B, and D. 5-FU can be combined with IFN using 24- and 48-h high-dose and long-term low-dose CI schedules, with large differences in dose intensity at maximum tolerated dose. Shorter infusions produce less mucosal and more hematological toxicity. Tumor responses were seen on both short- and long-term CI schedules. Future studies can establish the efficacies of these new schedules of 5-FU/IFN administration in specific tumor types.

Authors+Show Affiliations

Division of Hematology/Oncology, Department of Medicine, University of New Mexico School of Medicine and Cancer Center, Albuquerque, New Mexico 87131, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Clinical Trial, Phase I
Journal Article

Language

eng

PubMed ID

9816023

Citation

Greenblatt, M S., et al. "Phase I Evaluation of Therapy With Four Schedules of 5-fluorouracil By Continuous Infusion Combined With Recombinant Interferon Alpha." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 1, no. 6, 1995, pp. 615-20.
Greenblatt MS, Mangalik A, Ferguson J, et al. Phase I evaluation of therapy with four schedules of 5-fluorouracil by continuous infusion combined with recombinant interferon alpha. Clin Cancer Res. 1995;1(6):615-20.
Greenblatt, M. S., Mangalik, A., Ferguson, J., & Elias, L. (1995). Phase I evaluation of therapy with four schedules of 5-fluorouracil by continuous infusion combined with recombinant interferon alpha. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 1(6), 615-20.
Greenblatt MS, et al. Phase I Evaluation of Therapy With Four Schedules of 5-fluorouracil By Continuous Infusion Combined With Recombinant Interferon Alpha. Clin Cancer Res. 1995;1(6):615-20. PubMed PMID: 9816023.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phase I evaluation of therapy with four schedules of 5-fluorouracil by continuous infusion combined with recombinant interferon alpha. AU - Greenblatt,M S, AU - Mangalik,A, AU - Ferguson,J, AU - Elias,L, PY - 1995/6/1/pubmed PY - 1998/11/17/medline PY - 1995/6/1/entrez SP - 615 EP - 20 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 1 IS - 6 N2 - The purpose of this study was to determine the maximum tolerated dose and dose-limiting toxicities of 5-fluorouracil (5-FU) when administered concurrently with recombinant IFN-alpha using four continuous infusion (CI) dosing schedules of 5-FU. Forty-five patients with advanced or refractory cancers were treated with 5-FU by CI, plus IFN during the infusion only, by one of four schedules: schedule A: 24-h 5-FU infusion repeated weekly, 9 x 10(6) units IFN x 2 doses weekly; schedule B: 48-h 5-FU infusion repeated weekly, 9 x 10(6) units IFN x 4 doses weekly; schedule C: 5-day 5-FU infusion repeated every 3 weeks, 9 x 10(6) units IFN three times weekly; and schedule D: 21-day 5-FU infusion, repeated after 7 days off therapy, 9 x 10(6) units IFN three times weekly. At least three patients were treated at all dose levels. Doses of 5-FU were escalated to the next level if less than one half of the patients at a given level developed grades 2-4 toxicity. The maximum tolerated dose for 5-FU was 2150 mg/m2/week for schedule A (24-h CI), 2350 mg/m2/week for schedule B (48-h CI), 750 mg/m2/day for schedule C (5-day CI), and 175 mg/m2/day for schedule D (21-day CI). Median delivered dose intensities at these levels were 1788 mg/m2/week for schedule A, 2192 mg/m2/week for schedule B, 1250 mg/m2/week for schedule C, and 593 mg/m2/week for schedule D. The dose-limiting toxicities were hematological and gastrointestinal (stomatitis, diarrhea, nausea, anorexia) for schedules A and B and gastrointestinal (mostly stomatitis) for schedules C and D. Severe fatigue due to IFN was rare. Responses correlated with toxicity >/= grade 2, but not with increased dose intensity. Responses were noted in several tumor types on schedules A, B, and D. 5-FU can be combined with IFN using 24- and 48-h high-dose and long-term low-dose CI schedules, with large differences in dose intensity at maximum tolerated dose. Shorter infusions produce less mucosal and more hematological toxicity. Tumor responses were seen on both short- and long-term CI schedules. Future studies can establish the efficacies of these new schedules of 5-FU/IFN administration in specific tumor types. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/9816023/Phase_I_evaluation_of_therapy_with_four_schedules_of_5_fluorouracil_by_continuous_infusion_combined_with_recombinant_interferon_alpha_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=9816023 DB - PRIME DP - Unbound Medicine ER -