A variety of chemotherapeutic agents were examined in combination with asparaginase (EC-2) using P1798 lymphosarcoma in BALB/c mice as a test system with the aim of attaining remissions of long duration. Since it is possible to obtain permanent remissions in this system with large doses of EC-2. the level of enzyme administered was reduced so that the experimental results could be more closely correlated to the human disease response. The best results were obtained when asparaginase was given as the primary therapy with the other agents given subsequently. Second agents administered simultaneously with EC2 were not as beneficial as sequential or alternate therapy. Triple, sequential therapy was found superior to double therapy, and high incidences of permanent remiwions were obtained when azotomycin (71%), cytosine arabinoside (78%), Cytoxan (64%), or 5-Fluorouracil (78%) were given subsequent to EC2 but before vincristine.
LTHOUGH HIGH INCIDENCE OF REMISSION OF
A acute lymphatic leukemia has been achieved with L-asparaginase (EC-2), these remissions have been of short duration.616 13 In this study a variety of anti-cancer drugs have been used in combination with asparaginase in an effort to prolong the period of remission. The asparaginase-sensitive, corticoid-sensitive strain of the mouse lymphosarcoma PI798 was used as the test system. The asparaginase level used was adjusted so that the response to single therapy was similar to that reported from clinical studies. Chemotherapeutic agents tested as possible combina-From the