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Augmentation of Cytotoxicity of Chemotherapy by Human -Interferons in Human Non-Small Cell Lung Cancer Xenografts

Imperial Cancer Research Fund, Medical Oncology Unit, Department of Clinical Oncology, Western General Hospital, Edinburgh EH4 2XU, Scotland, United Kingdom

Three human non-small lung cancer xenograft lines were used to study the activity of combinations of cytotoxic drugs with human -interferons (IFNs). Statistically significant potentiation of cis-platinum (CDDP) and cyclophosphamide (CY) given weekly in a low dose was seen when human lymphoblastoid interferon (IFN-nl)(2 x 10⁵ µ/mouse/day) was administered simultaneously. The median tumor doubling times for CDDP in the three tumors (35, 22, and 29 days) increased to 52, 51, and 41 days when IFN-nl was added. A similar though less marked effect was seen with CY (median doubling time increased from 21.5, 19.5, and 27 days to 32, 27, and 35 days with the addition of IFN-nl). IFN-nl alone at this dosage was shown to have some cytotoxic activity. Similar potentiation of CDDP and ifosfamide was seen in two tumors when human recombinant -2 interferon was added at a lower dose (2 x 10⁴ µ/mouse/day). Median doubling times for CDDP increased from 17 and 14 days to 27 and 18.5 days with the addition of human recombinant -2 interferon, whereas for ifosfamide they increased from 11.5 and 14 days to 15 and 16 days. Human recombinant -2 interferon in this dose had no effect as a single agent.

¹ Present address: National Cancer Institute, National Cancer Institute-Navy Medical Oncology Branch, Naval Hospital, Bethesda, MD 20892.

² Present address: Imperial Cancer Research Fund, Laboratory of Molecular Pharmacology and Drug Metabolism, University of Edinburgh, Department of Biochemistry, Hugh Robson Building, George Square, Edinburgh, Scotland, United Kingdom.

³ Imperial Cancer Research Fund, Lincoln's Inn Fields, London, England, United Kingdom.

⁴ To whom requests for reprints should be addressed.

Received 1/ 4/86. Revised 6/ 3/86. Accepted 6/16/86.