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Phase I Study of Difluoromethylornithine in Combination with Recombinant 2a-Interferon¹

Mayo Clinic, Rochester, Minnesota 55905

24 patients with advanced, histologically proven cancer were treated with difluoromethylornithine 2.25 g/m² orally every 6 h for the first 7 days of each 4-week treatment cycle. These patients also received daily i.m. doses of recombinant human 2a-interferon (IFN) on Days 3 through 7 of each cycle. IFN doses of 3, 6, 12, 24, 36, and 48 x 10⁶ units/m² have been studied utilizing three patients at each daily dose level. Three additional patients have been observed at each of the two highest doses for better toxicity definition.

This combination produced slight transient declines in leukocyte and platelet counts and transient rises in serum aspartate aminotransferase; however, these changes were no more pronounced at the higher IFN doses than at daily doses of 6 x 10⁶ units/m². Mild nausea and vomiting occurred in most patients and mild diarrhea also was common at all IFN dose levels. Chills, fever, myalgia, lethargy and fatigue, and anorexia were also observed at all IFN doses; however, lethargy and fatigue (lassitude) seemed to be the major factor which limited patient tolerance of IFN to 48 x 10⁶ units/m² daily. No ototoxicity was identified clinically or audiometrically and no life-threatening toxicity has occurred. Initial Phase II studies in melanoma are currently in progress.

¹ Supported in part by Grant CA1508302 from the National Cancer Institute.

² To whom requests for reprints should be addressed, at Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905.

Received 3/28/88. Revised 8/ 3/88. Accepted 8/ 9/88.