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Cladribine (Single Agent)

Last updated on October 8, 2021


Cladribine (Ortho Biotech’s Leustatin, Japananssen-Cilag’s Leustatin/ Leustatine/Leustat, generics; also known as chlorodeoxyadenosine and 2-CDA)  is primarily used to treat hairy-cell leukemia. Cladribine is used much less frequently than fludarabine for chronic lymphocytic leukemia because many more, and larger, randomized trials have evaluated the latter agent. It has now been approved.

Mechanism Of Action

Cladribine is a purine analogue that closely resembles fludarabine; it inhibits DNA synthesis by interfering with DNA polymerases, thereby preventing the elongation of DNA strands.

Cladribine (Single Agent)Clinical Performance

A multicenter, randomized prospective study analyzed the efficacy and toxicity of cladribine plus prednisone versus chlorambucil plus prednisone in previously untreated patients with progressive or symptomatic chronic lymphocytic leukemia. As with other study designs, patients were randomized to receive either therapy; evaluated after a certain number of courses (in this case, three); and switched to the alternate therapy arm if they had not responded.

As mentioned previously, this method obscures the interpretation of long-term survival data. However, in the initial evaluation following three courses of therapy, 59/126 (47%) patients receiving cladribine plus prednisone achieved a CR and 50/126 (40%) achieved a PR, giving a total response rate of 87%. In the chlorambucil plus prednisone arm, 12/103 (12%) patients achieved a CRs and 46/103 (45%) of patients achieved a PR, giving an overall response rate of 57%. In addition, early relapses occurred more frequently in the chlorambucil arm than in the cladribine arm.

Patients who did not respond to first-line treatment with either regimen were switched to the alternate arm of the study. Second-line treatment with cladribine plus prednisone was found to be more effective (10/43 CR, 19/43 PR) than chlorambucil plus prednisone (0/26 CR and 7/26PR).

Response rates in the cladribine arm were comparable to responses obtained in patients receiving fludarabine. Although both the overall response rates and progression-free survival improved in the cladribine arm, this improvement did not translate into a significant difference in terms of overall survival rates. This effect may be associated with the switching of patients from one arm to another early on in the study.

Analysis of the drug-induced toxicity confirmed cladribine’s myelosuppressive effects, which resulted in a high incidence of neutropenia and infections compared with patients in the chlorambucil arm. Thrombocytopenia occurred with equal frequency in both arms.

Several Phase II studies have examined the efficacy of cladribine in combination chemotherapy in regimens such as cladribine/cyclophosphamide and cladribine/cyclophosphamide/mitoxantrone. In untreated patients, the former regimen produced overall response rates of 88%, with a CR of 29%. Large-scale, randomized trial data are lacking for this drug.

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