Suppression of in vitro peripheral blood lymphocyte mitogenesis by cytotoxic drugs commonly used in the treatment of breast cancer: a comparative study.

Cultures of normal donor peripheral blood mononuclear cells were tested in vitro for suppression by chemotherapeutic agents or their metabolites. The drugs tested were those commonly used in the treatment of breast cancer, namely, 5-fluorouracil, doxorubicin, vincristine, methotrexate and cyclophosphamide (actually testing its active metabolite, 4-hydroxy-cyclophosphamide). The lymphocytes were stimulated by phytohaemagglutinin (PHA), and the inhibitory effect of the drugs on subsequent DNA synthesis was measured by tritiated thymidine uptake. Drug concentrations used were equivalent to expected in vivo plasma and body fluid levels following i.v. injection of a standard therapeutic dose. Results suggest that the drugs may be ranked for suppression of T-cell function as follows: doxorubicin greater than vincristine = cyclophosphamide greater than 5-fluorouracil greater than methotrexate.