The combined use of interferon and radiotherapy in cancer management.
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.
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
D007370:Interferon Type I; D011994:Recombinant Proteins