Cyclophosphamide bimodal effects in antineoplasic therapy

Abstract

Cyclophosphamide (Cy), one ofthe chemotherapeutic agents more frequently used in clinical oncology, was originated after the Chemical strueture of mechlorethamine was modified to obtain an anticancer agent with higher selectivity for neoplastic tissues. The systematic use of chemotherapeutic drugs in cancer treatment made apparent that these compounds, given in large doses, usually cause impairment of the host defense mechanisms as a consequence of the inhibition of cellular proliferation. Nevertheless, it was demonstrated in several experimental models, that the administration of a single-low dose of Cy to tumor bearing animais, when the antitumoral immune response has fully developed, produces an immunopotentiation through a selective inhibition of T suppressor lymphocytes. Moreover, the observation of a total inhibition of metastases formation without altering the primary tumor growth, demonstrated an interesting new effect of such therapeutic modality: its preferential action against tumoral cells with metastatic phenotype, probably to a selective immunomodulation on these cellular subpopulations. These findings indicate a bimodal effect of Cy: depending on the dose and schedule of administration, it causes immunodepression or immunopotentiation. The use of biological response modifiers has led to what nowadays is know as the fourth therapeutic modality against cancer. It is proposed that Cy should also be considered within that context.