Mitoxantrone, vincristine, and dexamethasone in patients with refractory lymphoma

Twenty-seven patients with failed malignant lymphomas (19 with intermediate grade, 4 with low-grade, 3 with high-grade lymphomas, and 1 with Hodgkin's disease) who had failed a median of 3 prior multidrug regimens, all previously exposed to anthracyclines (median prior doxorubicin 360 mg/m2), were treated with a combination of mitoxantrone (M), vincristine (V), and dexamethasone (D) every 4 weeks. Mitoxantrone was given in a 3 times daily schedule (days 1-3), at doses between 5 and 10 mg/m2/day; vincristine, 2-mg total dose, was given on day 1 and day 8; dexamethasone, 20 mg/m2, was given on days 1-5. A total of 71 courses was administered; there were 4 complete responses (CR) and 14 partial responses (PR) (response rate 66%). At the highest doses, hematological toxicity was severe (5 patients died while pancytopenic); the nadir for WBC and platelets was on day 13, with a median hematological recovery on day 23. There were transient hepatic, renal, and oral toxicities; vincristine-related neuropathy was seen in 8 patients. All patients had normal prestudy cardiac function, as assessed by gated pool scans; follow-up scans showed a greater than 15% decrease of the left ventricular ejection fraction (LVEF) in 2 patients, without evidence of cardiac dysfunction. Although responses lasted a median of 10 weeks (range 4-37), our data indicate that mitoxantrone, at the doses and schedules used, is an effective drug in malignant, doxorubicin-resistant lymphomas. This observation warrants the use of mitoxantrone in the upfront treatment of malignant lymphoma.