Cancer Chemotherapy and Pharmacology

, Volume 33, Issue 3, pp 203–209 | Cite as

Escalating doses of interferon alpha-2A with cisplatin and concomitant radiotherapy: a phase I study

  • Everett E. Vokes
  • Daniel J. Haraf
  • Philip C. Hoffman
Original Articles Interferon, Cisplatin, Radiotherapy

Abstract

In this phase I study, we added escalating doses of interferon-alpha2A (IFN) to cisplatin and twice-daily radiotherapy based on the following rationale. Radiation enhancement has been shown for both interferon and cisplatin; in addition, potentiation of the cytotoxic activity of cisplatin by interferon has been demonstrated. A total of 48 patients with advanced solid tumors were treated with radiotherapy in 2 daily fractions of 125 cGy plus cisplatin at 8–10 mg/m2 per day delivered on 3 different schedules (continuous infusion, daily short-term infusion, and single short-term infusion of 50 mg/m2). IFN was injected s.c. 2h preceding the first daily fraction of radiation. IFN doses ranged from 0 to 5.0×106 U/m2 per day. All therapy was given over 5 days of every other week until completion of the radiotherapy. Treatment at all dose levels was well tolerated during cycles 1 and 2, with no instance of acute grade 3 or 4 toxicity being noted. However, cumulative myelosuppression in patients receiving more than two treatment cycles was seen at all dose levels and was attributed to the repeated administration of cisplatin. Alteration of the cisplatin schedule did not allow for further dose escalation of cisplatin. Our recommended doses are cisplatin given at 8 mg/m2 per day as a continuous infusion with IFN at 5.0×106 U/m2 per day. Among 24 patients with non-small-cell lung cancer, 2 had a complete response, 9 had a partial response, and 7 had stable disease. We conclude that this concomitant cisplatin-IFN-radiotherapy regimen is feasible. Activity was seen in non-small-cell lung cancer, and further studies of this regimen in that disease appear indicated.

Keywords

Lung Cancer Interferon Dose Level Continuous Infusion Dose Escalation 

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Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Everett E. Vokes
    • 1
    • 2
  • Daniel J. Haraf
    • 2
  • Philip C. Hoffman
    • 1
  1. 1.Department of Medicine, Section of Hematology/OncologyUniversity of ChicagoChicagoUSA
  2. 2.Department of Radiation and Cellular OncologyUniversity of ChicagoChicagoUSA

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