The Immune Response and the Therapeutic Effect of Metronomic Chemotherapy With Cyclophosphamide

Metronomic chemotherapy (MCT) is a novel therapeutic strategy for cancer treatment endowed with an antiangiogenic effect. It refers to regular administration of low doses of cytotoxic drugs, with minimal or no drug-free breaks. Previously, we demonstrated the immunomodulating activity of a single low-dose of cyclophosphamide (Cy) and the antitumor effect of MCT with Cy on established rat lymphomas and sarcomas. Here, we examined whether the immune response is responsible for the antitumor effect of MCT with Cy on L-TACB lymphoma. Inbred e rats and nude mice were subcutaneously challenged with L-TACB. After 7 days, they were distributed into two experimental groups: 1) treated animals, which were injected IP with Cy (10 mg/kg body weight) three times per week, and 2) control animals, which received IP saline injections. Exponential growth and decay and tumor doubling time were calculated. Also, serum IL-10 levels were measured. One hundred percent of treated rats showed tumor regression versus 0% of control rats. The increase of tumor-induced IL-10 levels was reverted by the treatment with Cy. On the other hand, there were no tumor regressions, in treated or control nude mice. However, the tumor doubling times of treated nude mice were significantly higher than those of control mice, implying that other antitumor mechanism(s), independent of the adaptive immune response, might be taking place. Our present results indicate that modulation of the immune response would be involved in the antitumor effect of MCT with Cy, because the absence of the specific immune response impairs, at least in part, its therapeutic effect in a lymphoma tumor model.