Fludarabine and cladribine in relapsed/refractory low-grade non- Hodgkin's lymphoma: A phase II randomized study

Background: It is unclear whether the purine analogs fludarabine (Flu) and cladribine (CdA) are non-resistant. Patients and methods: Sixty patients with relapsed or refractory low-grade NHL were randomly allocated to initial treatment with either Flu 25 mg/m², or CdA 0.14 mg/kg, each for five consecutive days every four weeks. Upon treatment failure, eligible patients were crossed over to the other study drug. Results: Overall response and CR were 68% and 48% with Flu, and 72% and 38% with CdA, respectively. For responders, actuarial three-year progression-free survival was 58% with Flu and 52% with CdA. Treatment with both drugs was well tolerated, with toxic effects primarily hematological. Two patients (8%) in the Flu group and 15 patients (47%, P = 0.001) in the CdA group were taken off study because of persistent hematological toxicity. After cross over, none of seven refractory patients responded, while eight of nine previously responsive patients achieved second responses. Conclusions: Our study confirms that Flu and CdA have similar response rates and durations. However, further studies are required to optimize the CdA schedule and dosage in order to ameliorate its toxic profile while maintaining antitumor activity. The two drugs appear to be cross-resistant.