title: A pilot study of interferon alpha-2a, fluorouracil, and leucovorin given with granulocyte-macrophage colony stimulating factor in advanced gastrointestinal adenocarcinoma.
abstract: We reported previously that the addition of recombinant Escherichia coli human granulocyte-macrophage colony stimulating factor (GM-CSF) to a 5-fluorouracil (5-FU) and leucovorin (LV) regimen seemed to ameliorate diarrhea and permit increased 5-FU dose intensity (J. L. Grem et al., J. Clin. Oncol., 12: 560-568, 1994). We then tested the effect of GM-CSF given with a more toxic regimen of 5-FU/LV/IFN-alpha (IFN alpha-2a). Thirty-one patients with a good performance status and no prior chemotherapy for systemic disease received IFN alpha(-2a (5 MU/m2 s.c., days 1-7), 5-FU (370 mg/m2 i.v., days 2-6), LV (500 mg/m2 i.v., days 2-6), and GM-CSF (Saccharomyces cerevisiae 250 microg/m2 s.c., days 7-18) every 3 weeks. Toxicities and 5-FU dose intensity were compared with that observed in our prior Phase II trial with 5-FU/LV/IFN alpha-2a (J. L. Grem et al., J. Clin. Oncol., 11: 1737-1745, 1993). In comparison with the prior Phase II study, the WBC and granulocyte nadirs in the present trial were significantly higher. When trends in toxicity grades for all cycles were compared, stratifying for 5-FU dose, the incidence and severity of mucositis, skin rash, WBC toxicity, and granulocyte toxicity were significantly lower in the present trial, whereas nausea/vomiting and fatigue were significantly worse. The delivered 5-FU dose intensity for all cycles of therapy appeared to be significantly higher in the present trial. Six of 28 evaluable patients had a partial response (21.4%), and 13 (46%) had stable disease for > or =12 weeks. Despite treatment-related toxicity, patient quality of life did not worsen during the study. No correlation was observed between thymidylate synthase content in primary tumor specimens and response, time to treatment failure, or survival. The addition of GM-CSF appeared to decrease the severity of leukopenia, granulocytopenia, mucositis, and skin rash when compared with our prior experience with this regimen of 5-FU/LV/IFN alpha-2a, at the cost of greater nausea/vomiting and fatigue. The potential impact of increased 5-FU dose intensity on clinical response, however, remains to be determined.
authors.affiliation: Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Naval Medical Center, Bethesda, Maryland 20889, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Shapiro
authors.forename: N
authors.initials: N
authors.lastname: Harold
authors.forename: C
authors.initials: C
authors.lastname: Takimoto
authors.forename: J M
authors.initials: JM
authors.lastname: Hamilton
authors.forename: D
authors.initials: D
authors.lastname: Vaughn
authors.forename: A
authors.initials: A
authors.lastname: Chen
authors.forename: S M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: D
authors.initials: D
authors.lastname: Liewehr
authors.forename: C
authors.initials: C
authors.lastname: Allegra
authors.forename: B
authors.initials: B
authors.lastname: Monahan
authors.forename: A
authors.initials: A
authors.lastname: Lash
authors.forename: F
authors.initials: F
authors.lastname: Grollman
authors.forename: D
authors.initials: D
authors.lastname: Flemming
authors.forename: K
authors.initials: K
authors.lastname: Behan
authors.forename: P G
authors.initials: PG
authors.lastname: Johnston
authors.forename: D
authors.initials: D
authors.lastname: Haller
authors.forename: M
authors.initials: M
authors.lastname: Quinn
authors.forename: G
authors.initials: G
authors.lastname: Morrison
authors.forename: J L
authors.initials: JL
authors.lastname: Grem
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011788:Quality of Life; D011994:Recombinant Proteins; D013940:Thymidylate Synthase / Q000378:metabolism
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013940:Thymidylate Synthase; D002955:Leucovorin; D005472:Fluorouracil