The Role of Mitoxantrone in the Treatment of Indolent Lymphomas

Abstract

Abstract Learning Objectives After completing this course, the reader will be able to: Describe three regimens that use mitoxantrone in indolent lymphoma. List the NCCN-recommended regimens for the first-line treatment of follicular lymphoma. Discuss the side-effect profile of mitoxantrone in combination with other agents for indolent lymphoma. Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com With the introduction of newer therapeutic approaches, survival in indolent non-Hodgkin's lymphoma (NHL) appears to be improving. Mitoxantrone (Novantrone®; Serono, Inc.; Rockland, MA, http://www.seronousa.com), an anthracenedione with low cardiotoxic potential, has demonstrated activity in indolent NHL in combination with fludarabine (Fludara®; Berlex Laboratories; Wayne, NJ, http://www.berlex.com) and other agents. In a Southwest Oncology Group trial (SWOG 9501), treatment with fludarabine and mitoxantrone (FM) induced a complete remission (CR) rate of 44% and a partial remission (PR) rate of 50% in untreated patients. The estimated 4-year progression-free survival (PFS) rate was 38%. In a multicenter Italian trial comparing the efficacy of FM with that of cyclophosphamide, doxorubicin (Adriamycin®; Bedford Laboratories; Bedford, OH, http://www.bedfordlabs.com), vincristine (Oncovin®; Eli Lilly and Company; Indianapolis, IN, http://www.lilly.com), and prednisone (Deltasone®; Pfizer Pharmaceuticals; New York, NY, http://www.pfizer.com), CHOP, followed by rituximab (Rituxan®; Genentech, Inc.; South San Francisco, CA, http://www.gene.com) for patients with incomplete clinical or molecular responses, the CR and molecular response rates were significantly higher in the FM arm, but the PFS and overall survival (OS) rates did not differ between the two arms. However, FM was also significantly less toxic than CHOP. The administration of rituximab following chemotherapy resulted in higher clinical and molecular response rates in both arms. In a separate trial, FM plus dexamethasone (Decadron®; Merck and Co., Inc.; Whitehouse Station, NJ, http://www.merck.com), FND, plus concurrent rituximab produced a CR rate of 92%. In a randomized German study, patients with indolent lymphomas received FM plus cyclophosphamide (FCM) or FCM with rituximab. PFS and OS times were significantly better for patients who received combined chemoimmunotherapy. Mitoxantrone-based regimens are highly active and well tolerated in patients with both relapsed and previously untreated indolent lymphomas. The addition of rituximab appears to increase the activity of the FM, FND, and FCM regimens. Although the results of the Italian multicenter study support the superiority of FM over CHOP in terms of clinical and molecular responses and tolerability, additional studies using rituximab in combination with both of these regimens should be attempted to determine the possible further benefit of both in the management of indolent lymphoma. Because cure remains elusive in patients with indolent lymphoma, maximum prolongation of PFS with minimal toxicity and maximum preservation of quality of life should remain central goals of treatment.