title: Biomodulation with sequential intravenous IFN-alpha2b and 5-fluorouracil as second-line treatment in patients with advanced colorectal cancer.
abstract: A phase II trial was carried out by the Grupo Oncologico Cooperativo del Sur (G.O.C.S.) to assess the efficacy and toxicity of a biochemical modulation of 5-fluorouracil (5-FU) by i.v. pretreatment with interferon (IFN)-alpha2b in patients with advanced colorectal carcinoma refractory to previous therapy with 5-FU modulated by methotrexate (MTX) or leucovorin (LV) or both. Between January 1993 and October 1995, 34 patients were entered on the study. The treatment was IFN-alpha2b 5 x 10(6)/m2 IU in a 1-h i.v. infusion, followed immediately by 5-FU 600 mg/m2 i.v. bolus injection. Courses were repeated weekly until observation of progressive disease or severe toxicity. One patient could not be assessed for response. Objective regression was observed in 2 of 33 patients (6%, 95% confidence interval, 0%-14%). No patient achieved a complete response. Two patients had partial responses (6%). No change was recorded in 14 patients (41%), and progressive disease occurred in 17 (52%). The median time to treatment failure was 3 months, and the median survival was 5 months. Toxicity was within acceptable limits. The main side effects were mucositis and diarrhea. Four episodes of grade 2 stomatitis were observed, causing dosage modifications. The most frequent toxic effects attributable to IFN-alpha2b were mild fatigue and fever. In conclusion, second-line therapy with i.v. IFN-alpha2b preceding 5-FU has shown an interesting profile of activity in a patient population with clearly unfavorable characteristics. From this perspective, further appropriately designed studies are needed to identify the greatest potential of IFN-alpha2b as a modulator of 5-FU.
authors.affiliation: Grupo Oncológico Cooperativo del Sur, Neuquén, República Argentina.
authors.forename: J E
authors.initials: JE
authors.lastname: Pérez
authors.forename: J A
authors.initials: JA
authors.lastname: Lacava
authors.forename: M E
authors.initials: ME
authors.lastname: Domínguez
authors.forename: R
authors.initials: R
authors.lastname: Rodríguez
authors.forename: M R
authors.initials: MR
authors.lastname: Barbieri
authors.forename: L A
authors.initials: LA
authors.lastname: Romero Acuña
authors.forename: J M
authors.initials: JM
authors.lastname: Romero Acuña
authors.forename: M J
authors.initials: MJ
authors.lastname: Langhi
authors.forename: S
authors.initials: S
authors.lastname: Amato
authors.forename: N
authors.initials: N
authors.lastname: Marrone
authors.forename: E H
authors.initials: EH
authors.lastname: Ortiz
authors.forename: B A
authors.initials: BA
authors.lastname: Leone
authors.forename: C T
authors.initials: CT
authors.lastname: Vallejo
authors.forename: M R
authors.initials: MR
authors.lastname: Machiavelli
authors.forename: A O
authors.initials: AO
authors.lastname: Romero
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D019233:Retreatment
chemical_list: D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D005472:Fluorouracil