[Mitoxantrone in the treatment of relapsed and refractory malignant lymphoma]

Mitoxantrone is an anthracenedione with structural similarities to adriamycin but without the amino-sugar moiety on the parent molecule. The compound attracted attention on the basis of animal tumor studies in which it showed equal or superior efficacy compared to adriamycin, but with diminished cardiotoxicity; and it was not fully cross-resistant to adriamycin. Our in vitro studies using human small cell lung cancer cell line (SBC-3) disclosed the absence of cross-resistance between mitoxantrone and adriamycin: SBC-3/ADM, which had developed resistance by continuous exposure to increasing concentration of adriamycin, was as equally sensitive to mitoxantrone as SBC-3 was when tested by clonogenic assay. A phase II study conducted in our Department revealed that mitoxantrone was active to malignant lymphoma refractory to conventional agents including adriamycin: 6 (33%) of 18 patients responded to the agent. Based on the results of our phase II studies of mitoxantrone, etoposide, and cisplatin in malignant lymphoma, we have conducted a phase III study of a 4-drug combination of these 3 drugs plus prednisolone in relapsed or refractory lymphoma: Out of 14 patients, 3 responded completely and 4 did partially, so far. The regimen would appear useful as a salvage therapy for refractory lymphoma.