Effects of a combination of cyclophosphamide and human recombinant interleukin 2 on pulmonary metastasis after the surgical removal of a 3-methylcholanthrene-induced primary tumor in autochthonous mice.

We have investigated the therapeutic effects of a combination of cyclophosphamide (CY, 150 mg/kg, iv) and human recombinant interleukin 2 (IL-2, 5 x 10(4) JU/day, ip for 5 days) on autochthonous tumors induced in mice by 3-methylcholanthrene. The initial treatment was carried out when the tumor had reached 8 to 10 mm in diameter. Twenty-eight out of 35 mice (80%) died of local recurrence and pulmonary metastasis of tumor cells within 53 +/- 40 days (mean survival time, MST +/- SD) after the surgical removal of the primary tumor. When these mice were treated with both CY and IL-2 following the operation (Op), only 10 out of 20 mice (50%) died of recurrence and metastasis. The survival rate, however, was not improved by CY chemotherapy alone or IL-2 immunotherapy alone, although each provided a prolongation of the MST. Natural killer cell and LAK precursor cell activities in the spleen cells from the treated mice were found to be restored by IL-2 alone or CY + IL-2, whereas they were suppressed by CY alone. These findings reveal that the restoration of the antitumor activity of spleen cells does not provide an improved therapeutic effect by itself and that IL-2 immunotherapy requires the associated effect of CY chemotherapy to achieve an improved therapeutic effect.