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Pharmacokinetics, Single-Dose Tolerance, and Biological Activity of Recombinant -Interferon in Cancer Patients¹

Department of Clinical Immunology and Biological Therapy, University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77030 [R. K., M. G. R., A. R., M. T., J. R. Q., J. U. G.], and Genentech, Inc., South San Francisco, California 94080 [S. A. S.]

We report a clinical study of the pharmacokinetics, toxicity, and biological activity of i.v.- and i.m.-administered recombinant -interferon (rlFN-) consisting of 143 amino acids. Ten patients with metastatic cancer were given rlFN- at doses of 0.01 to 2.5 mg/sq m by alternating i.m. and i.v. bolus injections with a minimum intervening period of 72 h. After i.v. administration, rlFN- was cleared monoexponentially with a short half-life of 25 to 35 min as determined by bioassay and enzyme immunoassay. After i.m. injection, a longer half-life of 227 to 462 min was measured by enzyme immunoassay. Serum titers were detected by bioassay only at high doses, suggesting partial loss of antiviral activity at the i.m. site. However, other biological effects were retained as evidence by fever, chills, and fatigue after both routes of administration and granulocytopenia after i.m., but not i.v., doses. Two of ten patients showed objective evidence of tumor regression. These data suggest that further studies with i.m. as well as prolonged i.v. infusions of rlFN- are indicated.

¹ This work was supported by a grant from Genentech, Inc. Research conducted, in part, by the John D. and Catherine T. MacArthur Foundation, the Clayton Foundation for Research, and the James E. Lyon Foundation for Research.

² To whom requests for reprints should be addressed, at Department of Clinical Immunology and Biological Therapy, Box 41, M. D. Anderson Hospital and Tumor Institute, 6723 Bertner Avenue, Houston, TX 77030.

³ Senior Clayton Foundation Investigator.

Received 11/19/84. Revised 2/28/85. Accepted 3/ 4/85.

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