2-chlorodeoxyadenosine as initial therapy for advanced low grade lymphomas

In order to evaluate efficacy and safety of 2-chlorodeoxyadenosine (2-CdA) as primary therapy of low grade non Hodgkin's lymphoma, a phase II trial of 2-CdA was initiated in patients with previously untreated advanced low grade lymphoma. Fourteen previously untreated patients with stage III and IV low grade lymphoma were enrolled. Patients received 2-CdA 0.1 mg/kg/d by continuous infusion for 7 days every 28 days, for 1-6 cycles of therapy (median 3.5). Results showed one complete response and nine partial responses for an overall response rate of 75%. Until now there have only been three responding patients who have had progressive disease, with a median follow-up time of 18 months. The major toxicity was bone marrow suppression and nine patients stopped therapy prior to a planned six cycles because of prolonged cytopenias, primarily thrombocytopenia. Fifteen of 50 cycles of therapy were associated with neutropenic febrile episodes and there was one septic death secondary to Listeriosis. It seems from this small group of patients that 2-CdA is an active agent in previously untreated low grade lymphoma. Myelosuppression is cumulative and limits the number of cycles of therapy which can be given. Future exploration of different doses or schedules of this active agent is warranted.