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

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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.

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Authors and Affiliations

  1. University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin, USA

    Joan H. Schiller, Dan Burns & Marilyn Larson

  2. William S. Middleton VA Hospital, Madison, Wisconsin, USA

    Joan H. Schiller

  3. Dana Farber Cancer Institute, Boston, Massachusetts, USA

    Donna Neuberg

  4. Medical College of Wisconsin, Milwaukee, Wisconsin, USA

    Paul Ritch

  5. Allegheny Singer Research Institute, Pittsburgh, Pennsylvania, USA

    Mark Levitt

  6. Albert Einstein College of Medicine, Bronx, New York, USA

    Janice Dutcher

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  1. Joan H. Schiller
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Schiller, J.H., Neuberg, D., Burns, D. et al. An Eastern Cooperative Oncology Group phase I trial of all-trans-retinoic acid and interferon-alpha: E2Y92. Invest New Drugs 15, 319–324 (1997). https://doi.org/10.1023/A:1005985418441

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