title: The combined use of interferon and radiotherapy in cancer management.
abstract: Preclinical studies have suggested combination therapy with interferon and radiation results in an enhanced cytotoxic effect. Both additive and synergistic effects have been reported in mammalian cells in tissue culture. A phase I trial was designed to determine patient tolerance to concomitant Schering interferon alfa-2b (Intron A) and radiation therapy (RT). RT was delivered in standard fashion (five times a week in 180 rad fractions). Interferon was injected subcutaneously 2 hours prior to irradiation. Sixteen patients, divided into groups of three, received interferon at dose levels of 2 X 10(6) to 30 X 10(6) IU/m2 given five or three times a week. Planned dose escalations were stopped at 5 X 10(6) IU/m2 by patient tolerance. We observed a significant difference in tolerance to treatment between the patients receiving interferon three times a week and those receiving interferon five times a week. Eight of nine patients treated five times a week developed grade III-IV toxicity resulting in hospitalization and discontinuation of interferon; radiation was not discontinued. Only two of seven patients treated three times a week were hospitalized, with grade II toxicity (anorexia), but both were subsequently able to continue treatment with both interferon and radiation. We have identified a maximum tolerated dose and schedule of interferon (5 X 10(6) IU/m2 three times a week) for use in future combined modality trials to assess the potential clinical effectiveness of interferon in combination with RT.
mesh_terms: D000328:Adult; D000368:Aged; D002460:Cell Line; D003131:Combined Modality Therapy; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D011836:Radiation Tolerance / Q000187:drug effects; D011994:Recombinant Proteins / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D007370:Interferon Type I; D011994:Recombinant Proteins