Nucleoside Analogs

There are currently three analogs of deoxyadenosine, i.e., fludarabine, cladribine, and pentostatin, in clinical use for the treatment of lymphoproliferative disorders. In patients with ATL, most experience has been obtained with pentostatin and the least with fludara-bine.93

Single-agent cladribine (2-chlorodeoxyadenosine) has limited activity in patients with relapsed or refractory acute or lymphomatous ATL (OR 7%; CR 0%).94,95 At least four studies have assessed the effectiveness of pentostatin (deoxycoformycin) monotherapy in patients with ATL.96-99 The majority of patients had either acute or lymphomatous subtypes, and had received prior therapy. Overall response rates were 15-20% with CR rates <10%. The majority of studies did not report OS.96,97,99

Given these encouraging results, a multicenter phase II trial evaluated the efficacy of pentostatin in combination with doxorubicin, vincristine, etoposide, and prednisolone in 60 patients with previously untreated ATL (34 acute, 21 lymphoma, and 5 chronic).100 Median age was 56 years (range 31-69 years). Fifty-nine patients were evaluable for response. Overall response was 52.5% (CR 28.8%; PR 23.7%). However, therapy was discontinued in 62.7% of patients—52.5% during induction therapy because of progressive disease and 10.2% because of toxicity. Only 17% completed the entire 10 cycles of therapy. Both median follow-up and median OS were 7.4 months. Therefore, pentostatin-containing regimens have limited activity in patients with ATL.

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