Clinical and toxicological aspects of the antineoplastic drug cladribine: a review

Cladribine (2-chlorodeoxyadenosine, 2-CdA) is a new antineoplastic drug which exerts its antilymphoproliferative 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 administration might be feasible. The drug is well tolerated, and myelosuppression was found to be the dose-limiting toxicity. Nonhematological toxicity, such as alopecia, nausea, vomiting, stomatitis, diarrhea, and organ toxicity is mild or absent. Cladribine has shown efficacy in phase-II studies in hairy cell leukemia [response rate (RR)=75–100% and complete response rate (CR)=46–92%], chronic lymphocytic leukemia (RR=37–67% and CR=4–39%), and lymphocytic lymphoma (RR=43–52% and CR=14–20%). Furthermore, there is preliminary evidence that cladribine 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 multiple myeloma cladribine was not effective. Comparative randomized studies 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.