title: Dexamethasone does not enhance antileukemic activity of cladribine in mice with leukemias L1210 and P388.
abstract: Combination of corticosteroids with new purine analogs such as cladribine 2-chlorodeoxyadenosine, (2-CdA) and fludarabine (FAMP) is controversial. The possibility of potentiation of antineoplastic activity of 2-CdA or FAMP by corticosteroids has not been documented so far. On the other hand, such combination may increase immunosuppression and the risk of infections. The aim of our study was to evaluate the influence of 2-CdA and dexamethasone (DEX) on the survival time of mice bearing lymphoid leukemias L1210 and P388. CD2F1 strain mice (132 male) were used in the experiment. The animals were injected i.p. on day 0 with 10(6) leukemic cells. The drugs were given on days 1-5 i.p. in the following concentrations: 2-CdA - 20 mg/kg, DEX 1.25 mg/kg, DEX 2.5 mg/kg, DEX 5 mg/kg, DEX 10 mg/kg, alone and in combination. The animals were observed daily for survival for a minimum of 30 days. The efficacy of the therapy against leukemia (defined as increase in lifespan - ILS) was assessed as the percentage of the median survival time (MST) of the treated group(t) to that of the control group(c): ILS(%) = (MSTt/MSTc) 100. The survival time of mice bearing L1210 or P388 leukemia treated with both drugs simultaneously was not longer than that of mice treated with either of drugs alone. Combination of 2-CdA and DEX in doses 5 and 10 mg/kg resulted in decrease of survival time of animals bearing P388 leukemia as compared with the control group without any treatment. Our study revealed that combination of 2-CdA with DEX in both leukemias is not more effective than 2-CdA alone. These results may indicate that routine addition of corticosteroids to purine analogs in the treatment of lymphoid malignancies is not warranted.
authors.affiliation: Department of Hematology, Medical University of Lodź, Poland. robaktad@psk2.am.lodz.pl
authors.forename: T
authors.initials: T
authors.lastname: Robak
authors.forename: A
authors.initials: A
authors.lastname: Szmigielska
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017338:Cladribine / Q000008:administration & dosage / Q000494:pharmacology*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004347:Drug Interactions; D007939:Leukemia L1210 / Q000188:drug therapy*; D007941:Leukemia P388 / Q000188:drug therapy*; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D016896:Treatment Outcome
chemical_list: D017338:Cladribine; D003907:Dexamethasone