Treatment of micrometastases from lewis lung carcinoma with abrin and cyclophosphamide, given singly and in combination

Abstract

The effect of the plant toxin abrin and of cyclophosphamide given as adjuvant chemotherapy after irradiation of the primary tumor was studied in mice bearing intramuscularly growing Lewis lung carcinoma. The chemotherapy was given immediately after irradiation performed 9 days after inoculation of 10⁵ tumor cells. The drugs were given in bolus injections either as single agents or concurrently. The therapeutic effect was assessed by recording the appearance of lung metastases on day 21 or the number of long-term survivors, i.e. animals alive at day 60. In the control group 21±3.4 (SD) macroscopic lung colonies was recorded on day 21. Mean survival time was 25.5 days with none of the mice alive at day 60. The optimal abrin dose (612.5 ng/kg IV) reduced the number of lung metastases to 2.3±0.8 and yielded 37% long-term survivors (11/30). The optimal dose of cyclophosphamide (150 mg kg IP) reduced the number of lung colonies to <1 and yielded 61% survivors (14/23). Small to moderate doses of abrin significantly potentiated the therapeutic effect of cyclophosphamide without increasing the toxicity. The best results (18/20 or 90% long-term survivors) were obtained when the optimal dose of cyclophosphamide, 150 mg/kg, was combined with 350 ng/kg of abrin. The results obtained in this highly resistant tumor suggest that combinations of the two drugs may be useful also in other tumor types.