CLINICAL AND TOXICOLOGICAL ASPECTS OF THE ANTINEOPLASTIC DRUG CLADRIBINE - A REVIEW

Cladribine (2-chlorodeoxyadenosine, 2-CdA) is a new antineoplastic dru g which exerts its anti-lymphoproliferative activity by its resistance to the enzyme adenosine deaminase. Cladribine is mostly administered as a 7-day continuous infusion and in a dose of 0.1 mg/kg/day. However , preliminary data show that the subcutaneous and oral routes of admin istration might be feasible. The drug is well tolerated, and myelosupp ression was found to be the dose-limiting toxicity. Nonhematological t oxicity, such as alopecia, nausea, vomiting, stomatitis, diarrhea, and organ toxicity is mild or absent. Cladribine has shown efficacy in ph ase-II studies in hairy cell leukemia [response rate (RR) = 75-100% an d complete response rate (CR) = 46-92%], chronic lymphocytic leukemia (RR = 37-67% and CR = 4-39%), and lymphocytic lymphoma (RR = 43-52% an d CR = 14-20%). Furthermore, there is preliminary evidence that cladri bine might be effective in the treatment of cutaneous T cell lymphoma (RR = 47% and CR = 20%), acute myeloid leukemia in children (RR = 59% and CR = 47%), acute lymphoid leukemia in children (RR = 14% and CR = 14%) and Waldenstrom macroglobulinemia (RR = 58% and CR = 3.5%). In mu ltiple myeloma cladribine was not effective. Comparative randomized st udies with established first-line and second-line therapeutic regimens are warranted and will define the ultimate place of cladribine in the therapy of malignant hematological disorders.