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

Three human non-small lung cancer xenograft lines were used to study the activity of combinations of cytotoxic drugs with human α-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-αnl)(2 × 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-αnl 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-αnl). IFN-αnl 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 α-2 interferon was added at a lower dose (2 × 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 α-2 interferon, whereas for ifosfamide they increased from 11.5 and 14 days to 15 and 16 days. Human recombinant α-2 interferon in this dose had no effect as a single agent.