An Eastern Cooperative Oncology Group Phase I trial of all-trans-retinoic acid and interferon-alpha: E2Y92

Joan H. Schiller, Donna Neuberg, Dan Burns, Paul Ritch, Marilyn Larson, Mark Levitt, Janice Dutcher

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

The Eastern Cooperative Oncology Group conducted a Phase I trial to determine the maximally tolerated doses of combination therapy with alpha interferon (IFN-α) and all-trans-retinoic acid (tRA). Fifty patients with incurable malignancies received IFN-α administered subcutaneously three times weekly, and tRA administered by mouth at bedtime. Doses were escalated between patient groups, starting at tRA dose level of 45 mg/m2 and 3 million units of IFN-α. Major, dose-limiting toxicities were attributable to either the tRA (rash, chelitis) or IFN (constitutional symptoms), and were observed only at tRA dose levels of 224 mg/m2 and 291 mg/m2, or 6 million units of IFN-α. The maximally tolerated dose level of 172.5 mg/m2 of tRA and 3 million units of IFN-α was well-tolerated, with no grade 3 or 4 toxicities attributable to therapy. One patient at the third dose level (75 mg/m2 of tRA and 3 million units of IFN-α) developed acute hepatic and renal failure and a metabolic encephalopathy of unclear etiology. We conclude that tRA and IFN-α may be safely administered together at the maximally tolerated dose of tRA as a single agent without unexpected side effects. The recommended doses of IFN-α and tRA for Phase II trials are 3 million units of IFN-α and 172.5 mg/m2 of tRA.

Original languageEnglish (US)
Pages (from-to)319-324
Number of pages6
JournalInvestigational New Drugs
Volume15
Issue number4
DOIs
StatePublished - Dec 1 1997

Keywords

  • Interferon-alpha
  • Phase I trial
  • Trans-retinoic acid

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'An Eastern Cooperative Oncology Group Phase I trial of all-trans-retinoic acid and interferon-alpha: E2Y92'. Together they form a unique fingerprint.

  • Cite this

    Schiller, J. H., Neuberg, D., Burns, D., Ritch, P., Larson, M., Levitt, M., & Dutcher, J. (1997). An Eastern Cooperative Oncology Group Phase I trial of all-trans-retinoic acid and interferon-alpha: E2Y92. Investigational New Drugs, 15(4), 319-324. https://doi.org/10.1023/A:1005985418441