Inhibition of C3H/He mouse mammary tumor growth by combined treatment with cyclophosphamide and polyadenylic-polyuridylic acid.

The antitumor effect of an immunomodulator, polyadenylic-polyuridylic acid, in combination with cyclophosphamide (CY) was studied in C3H/He mice bearing established mammary tumors. On Day 14 after tumor graft, mice received either CY (90 mg/kg) alone every 2 weeks for a total of four inoculations or alternate weekly inoculations of the same dose of CY and polyadenylic-polyuridylic acid (300 micrograms) or Bacillus Calmette-Guérin (400 micrograms) during 8 consecutive weeks. On Day 170, the following results were obtained. (a) Mice receiving CY alone showed significantly retarded tumor growth; nevertheless, 30 mice of 34 (88%) died of tumor, and only 1 mouse (3%) was tumor free. (b) In mice receiving combined CY and Bacillus Calmette-Guérin, no more significant tumor inhibition was observed than those receiving CY alone. (c) The most significant tumor inhibition was observed in mice receiving combined CY and polyadenylic-polyuridylic acid. Average tumor diameter on Day 63 was one-third (2 mm) of that of mice receiving CY alone (7 mm); 25 mice of 44 (57%) died of tumor; and 11 mice (25%) were tumor free. In in vitro 51Cr release assays using natural killer-sensitive YAC-1 target cells, cytotoxic activity of splenic nonadherent mononuclear cells of the tumor-bearing mice receiving the combined treatment was highly significantly increased. The importance of these findings relative to clinical application is considered.