Mitoxantrone, vinblastine and CCNU: long-term follow-up of patients treated for advanced and poor-prognosis Hodgkin's disease

Abstract

Advanced-stage or relapsed/refractory Hodgkin's disease (HD) has a poor prognosis despite aggressive chemotherapy regimens and the use of high-dose therapy with autologous stem cell support. Mitoxantrone, vinblastine and CCNU (lomustine) (MVC) combines the most effective chemotherapeutic agents of previous regimens for poor prognosis HD, and eliminates marginally active agents with unnecessary toxicities, such as bleomycin and dacarbazine. Sixty-eight patients with HD (23 newly diagnosed and 45 with relapsed/refractory disease, one patient treated both de novo and years later in relapse) were treated with the MVC regimen (mitoxantrone 8 mg/m²/day i.v. days 1 – 3; vinblastine 8 m/m²/day days 1 and 22; and CCNU (lomustine) 100 mg/m² on day 1, repeated at 6 – 8 weeks) in a single-arm Phase II study. All patients responded to treatment in the newly diagnosed group (overall response = 100%). The median response duration was not reached, but was in the range 7.6 – 180 + months, and median survival was 94 months. Eleven complete responses are ongoing at 39 – 180 + months. In the previously-treated patients, 41 responded to MVC (OR = 91%). The median response duration for this group was 11 months, and the median survival was 34 months after initiating MVC. Four secondary myeloid leukemias occurred, three in de novo, and one in the relapsed/refractory group, at a median follow-up of 14 years. MVC regimen for HD is highly active, for both de novo and relapsed/refractory disease, with high response rates and survival that compare favourably with the results obtained by high-dose therapy with stem-cell transplantation. Although significant, the toxicities associated with this regimen were manageable.

Keywords:

• Hodgkin's disease
• poor prognosis
• advanced stage
• mitoxantrone
• CCNU
• vinblastine
• MVC
• salvage therapy