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Phase I study of recombinant methionyl human consensus interferon (r-metHuIFN-Con1)
J A Neidhart1, S Schmidt, M Rosenblum
1Division of Medicine, University of Texas, M.D. Anderson Hospital and Tumor Institute, Houston.
Journal of Biological Response Modifiers
|June 1, 1988
Summary
This Phase I trial evaluated consensus interferon (r-metHuIFN-Con1) in advanced malignancy. The recommended Phase II dose is 30 mcg/m2/day, with manageable toxicities and potential for patient escalation.
Area of Science:
- Oncology
- Pharmacology
- Immunology
Background:
- Consensus interferon (r-metHuIFN-Con1) is a novel recombinant alpha interferon.
- Alpha interferons have shown activity in various malignancies.
Purpose of the Study:
- To determine the safety and tolerability of r-metHuIFN-Con1.
- To establish the recommended Phase II dose and schedule.
- To conduct preliminary pharmacokinetic and pharmacodynamic assessments.
Main Methods:
- Phase I clinical trial involving 21 patients with advanced malignancy.
- Dose escalation study with r-metHuIFN-Con1 administered intramuscularly on days 1-5 and 8-10 of a 28-day cycle.
- Intravenous, intramuscular, and subcutaneous administration for initial pharmacokinetic evaluation.
Main Results:
- Dose-limiting toxicities (vomiting, diarrhea) observed at 45 mcg/m2/day.
- Malaise, flu-like symptoms, nausea, and headache were frequent but tolerable at 30 mcg/m2/day.
- Pharmacokinetic studies showed absorption via subcutaneous and intramuscular routes; initial distribution phase (T1/2 alpha) was 4.9-9.0 minutes.
- 2'5'-Synthetase levels increased post-treatment; one partial response in gastrointestinal carcinoma.
Conclusions:
- The recommended Phase II starting dose for r-metHuIFN-Con1 is 30 mcg/m2/day.
- r-metHuIFN-Con1 demonstrates a manageable toxicity profile and potential for therapeutic benefit.
- Further investigation in Phase II trials is warranted.