Clinical studies of dichloromethotrexate (NSC 29630)

Dichloromethotrexate (DCM) is much superior to methotrexate (MTX) in inhibiting L1210 leukemia and C3H lymphosarcoma in mice. This greater effectiveness obtains for parenterally administered DCM and is much less apparent when DCM is given by mouth. The toxicity of DCM in animals is qualitatively similar to that produced by MTX. DCM is fifty to one hundred fold less toxic than MTX in rats and mice but only tenfold less toxic in dogs. It is concluded from clinical studies reported in this paper that: (1) The tolerated dose of DCM is fivefold that of MTX and the toxic manifestations are similar. (2) The tolerated doses of oral and iniramuscular DCM are equivalent. (3) Equitoxic, and presumably optimal, doses of oral DCM, oral MTX, and intramuscular DCM produce comparable antitumor effects in adults with lymphosarcoma and Hodgkin's disease. There is complete tumor regression in 10 to 20 per cent and partial regression in another 20 to 30 per cent of patients. These tumor regressions are, in general, short‐lasting. (4) The dose response relationship is steep. A twofold difference in dose of DCM or MTX results in a significant difference in toxicity and antitumor effect. (5) There are at least four other more effective modalities of treatment for lymphoma which should be employed before conventional folic acid antagonist therapy is considered.