INFLUENCE OF 2-CHLORODEOXYADENOSINE ALONE AND IN COMBINATION WITH CYTOSINE-ARABINOSIDE ON MURINE LEUKEMIAS L1210 AND P388

Background - The influence of 2-chlorodeoxyadenosine (2-CdA) and cytos ine arabinoside (Ara-C) on the survival time of mice bearing L1210 and P388 leukemias was investigated. Drugs were given alone and in combin ation (sequential therapy). Methods - 72 male CD2F1 strain mice were u sed in the experiments, They were given 2-CdA (20 mg/kg) on days 1-5 a fter inoculation with leukemic cells (day 0), i.p. or Ara-C (1000 mg/k g) on days 1, 4, 7, i.p. Drugs were administered alone and in combinat ion according to schedules given below : - 2-CdA and Ara-C at the same time in the doses given above; - 2-CdA before Ara-C : sequential ther apy (2-CdA on days 1-5, then Ara-C on days 6, 9, 12); - Ara-C before 2 -CdA : sequential therapy (Ara-C on days 1, 4, 7, then 2-CdA on days 8 -12). Results - The survival time of mice bearing L1210 or P388 leukem ia treated with Ara-C before 2-CdA was significantly prolonged as comp ared with animals receiving these agents separately, Prolongation of s urvival time of treated mice (ILS) compared with untreated was 157% in the case of L1210 and 175% in the case of P388. When both drugs were given at the same time or when 2-CdA was administered before Ara-C the survival time was not significantly longer than that obtained with dr ugs given separately. Conclusions - Our study revealed that, in both l eukemias tested, combined therapy according to the schedule : Ara-C gi ven before 2-CdA was more effective than monotherapy with either 2-CdA or Ara-C.