FLUDARABINE, MITOXANTRONE, AND DEXAMETHASONE - AN EFFECTIVE NEW REGIMEN FOR INDOLENT LYMPHOMA

Purpose: Although most patients with indolent lymphomas respond to ini tial therapy, virtually all experience relapse. Secondary therapy is o ften beneficial, but responses are rarely, if ever, durable. We conduc ted this phase II trial to evaluate the therapeutic efficacy and toxic ity of fludarabine, mitoxantrone, and dexamethasone (FND) in patients with relapsed indolent lymphoma. Patients and Methods: Fifty-one patie nts with recurrent or refractory indolent lymphoma were treated with a regimen of fludarabine 25 mg/m(2)/d intravenously (IV) on days 1 to 3 , mitoxantrone 10 mg/m(2) IV on day 1, and dexamethasone 20 mg/d IV or orally on days 1 to 5. Treatment was repeated at 4-week intervals for a maximum of eight courses. Late in the course of this trial, trimeth oprim-sulfamethoxazole (TMP-SMX) was incorporated for Pneumocystis car inii (PCP) prophylaxis. Results: Responses were complete (CR) in 24 pa tients (47%) and partial (PR) in 24 (47%). The median failure-free sur vival time was 21 months for CR patients and 9 months for PR patients. Notable activity of FND was seen even in the elderly, in those with h igh serum lactate dehydrogenase (LDH) or beta(2)-microglobulin levels, and in those with multiple prior treatment regimens. The predominant toxic effects were myelosuppression and infections; other toxic effect s were modest. Infections occurred in 12% of courses. Almost half of t he infections were proven or suspected opportunistic infections, inclu ding six cases of dermatomal herpes tester and two cases of proven PCP pneumonia. Conclusion: The FND combination is highly active in patien ts recurrent or relapsed indolent lymphoma and results in a high perce ntage of CRs. Because of the risk of opportunistic infections, we curr ently recommend prophylaxis with TMP-SMX and advise deletion of cortic osteroids for patients who develop opportunistic infections. (C) 1996 by American Society of Clinical Oncology.