[A phase II study of mitoxantrone in refractory and relapsed malignant lymphomas. Cooperative Study Group of...

A phase II clinical trial of mitoxantrone in refractory or relapsed malignant lymphomas was conducted by a cooperative study involving 17 institutions. Of 46 patients entered, 33 were evaluable for responses and toxicity. Thirty-one of the 33 had been previously exposed to adriamycin at a median dose of 220 mg/m2 (range 21-489 mg/m2), and two additional patients had each been given THP-adriamycin at a dose of 80 mg/m2 or 4'-epi adriamycin at a dose of 69 mg/m2. Mitoxantrone was administered in 3 different schedules: 8-12 mg/m2, every 3-4 weeks in 23 patients; 4-6 mg/m2, weekly, in 3 patients; and 2-4 mg/m2, for 5 days, in 7 patients. Summarizing the responses obtained in the 3 schedules, there were 2 partial responders among 5 with Hodgkin's disease, while there were 8 complete responders and 4 partial responders among 28 with non-Hodgkin's lymphoma. The overall response rate for all the evaluable patients was 42% with a complete response rate of 24%. The median response duration was 7+ weeks (range 4-27+ weeks) for complete responders and 7 weeks (range 4-46+ weeks) for partial responders. The major toxicity was myelosuppression: leukocytopenia less than 3,000/microliter occurred in 79% of patients, and thrombocytopenia less than 75,000/microliter in 35%. Other toxic effects were minimal, mild nausea and/or vomiting occurred in 39%, and diarrhea in 3%. Possible drug-related liver and renal dysfunctions were observed in 19% and 10%, respectively. The favorable response to mitoxantrone in patients with prior anthracycline antibiotic therapy suggests that the drug is not fully cross-resistant with anthracycline antibiotics, and that this drug is of value in combination with other drugs as a salvage therapy for patients with refractory or relapsed malignant lymphomas.