Serum displacing agents in cancer chemotherapy
Schiffman, F.J.; Fisher, J.M.; Rabinovitz, M.
Cancer Treatment Reports 61(7): 1407-1410
1977
ISSN/ISBN: 0361-5960 PMID: 563289 Document Number: 117936
The reproductive capacity of mouse leukemia cells treated with CPA [p-chlorophenoxyacetic acid] or CPB [p-chlorophenoxyisobutyric acid] and then chlorambucil was reduced by > 1 order of magnitude when compared to cells exposed to chlorambucil alone. The potentiation of chlorambucil cytotoxicity was not further increased when the concentration of CPA or CPB was raised from 400 to 800 .mu.M. Ultrafiltration studies indicated that CPA or CPB nearly doubled the concentration of free chlorambucil for each total concentration of the alkylating agent tested and it was the concentration of free chlorambucil which determined the degree of cytotoxicity whether or not the displacing agent was present. Administration of displacing agents such as CPA or CPB or their respective esterified derivatives, centrophenoxine and clofibrate, appears to be a useful adjunct for chemotherapy with alkylating agents since a greater portion of alkylating agent is made immediately available for action at target sites. Drug doses more closely represent chemotherapeutic pulses which might increase the therapeutic index by avoiding complications of persistence of highly toxic agents. Patients receiving clofibrate or related compounds might require alteration of the standard chlorambucil dosage.