Mitoxantrone in refractory nonHodgkin's lymphoma. A Southwest Oncology Group study

A phase II study of mitoxantrone in nonHodgkin's lymphoma was conducted by the Southwest Oncology Group between July 1981 and May 1982. The study involved 37 patients with histologically proven nonHodgkin's lymphoma, who were not eligible for higher priority protocols but had clearly measurable disease. Patients received mitoxantrone, 12 mg/m2 at intervals of 3 weeks, with a 10% increase in dose in the absence of myelosuppression and a 17% reduction for a WBC of less than 2 X 10(9) cells/L or a platelet count of less than 50 X 10(9)/L. The median number of previous regimens was three. Doxorubicin, in a median dose of 242 mg/m2 (range 12 to 650 mg/m2) had been previously given to 34 of the 37 patients. The Pathology Panel for Lymphoma Clinical Studies reviewed 31 (84%) of the lymphomas. Four of the ten follicular, small cleaved cell lymphomas responded compared with one of nine diffuse, large cell lymphomas. The median duration of response was 231 days. A median of two doses of mitoxantrone (range 1 to 18) was given. The median WBC nadir was 5.1 X 10(9)/L (range 04. to 9.4 X 10(9)/L), and the median lowest WBC for all doses was 2.4 X 10(9)/L (range 0.4 to 16 X 10(9)/L). Among 17 patients with a first WBC nadir of less than 3 X 10(9)/L, there were three partial responses compared with four responses (one complete, three partial) from nine patients with a WBC over 3 X 10(9)/L. There were seven responses (one complete, six partial) among 23 patients who had received up to three previous regimens, whereas only two of 14 patients receiving more than three previous regimens responded (one complete, one partial response). The response rate was independent of the previous dose of doxorubicin with five responses out of 23 patients who received a total dose of less than 300 mg/m2 and four responses out of 14 patients who received greater than 300 mg/m2. These data are compatible with the hypothesis that mitoxantrone alone is active against previously treated low-grade lymphomas and that the response rate is independent of the total dose of prior doxorubicin received and the degree of myelosuppression. Mitoxantrone may not be cross resistant with doxorubicin.