Mitoxantrone is superior to doxorubicin in a multiagent weekly regimen for patients older than 60 with high-grade lymphoma: results of a BNLI randomized trial of PAdriaCEBO versus PMitCEBO

• Published in: Blood 2001-05, Vol.97 (10), p.2991-2997
• Main Authors: Mainwaring, Paul N., Cunningham, David, Gregory, Walter, Hoskin, Peter, Hancock, Barry, Norton, Andrew J., MacLennan, Ken, Smith, Paul, Hudson, Gillian Vaughan, Linch, David
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Bleomycin - administration & dosage; Bleomycin - adverse effects; Bleomycin - therapeutic use; Chemotherapy; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Cyclophosphamide - therapeutic use; Disease-Free Survival; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Doxorubicin - therapeutic use; Etoposide - administration & dosage; Etoposide - adverse effects; Etoposide - therapeutic use; Female; Humans; Lymphoma, Non-Hodgkin - drug therapy; Lymphoma, Non-Hodgkin - mortality; Male; Medical sciences; Middle Aged; Mitoxantrone - administration & dosage; Mitoxantrone - adverse effects; Mitoxantrone - therapeutic use; Pharmacology. Drug treatments; Prednisolone - administration & dosage; Prednisolone - adverse effects; Prednisolone - therapeutic use; Prospective Studies; Remission Induction; Survival Rate; Vincristine - administration & dosage; Vincristine - adverse effects; Vincristine - therapeutic use
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V97.10.2991

A prospective, multicenter, randomized trial was undertaken to compare the efficacy and toxicity of adriamycin with mitoxantrone within a 6-drug combination chemotherapy regimen for elderly patients (older than 60 years) with high-grade non-Hodgkin lymphoma (HGL) given for a minimum of 8 weeks. A total of 516 previously untreated patients aged older than 60 years were randomized to receive 1 of 2 anthracycline-containing regimens: adriamycin, 35 mg/m2intravenously (IV) on day 1 (n = 259), or mitoxantrone, 7 mg/m2 IV on day 1 (n = 257); with prednisolone, 50 mg orally on days 1 to 14; cyclophosphamide, 300 mg/m2 IV on day 1; etoposide, 150 mg/m2 IV on day 1; vincristine, 1.4 mg/m2 IV on day 8; and bleomycin, 10 mg/m2 IV on day 8. Each 2-week cycle was administered for a minimum of 8 weeks in the absence of progression. Forty-three patients were ineligible for analysis. The overall and complete remission rates were 78% and 60% for patients receiving PMitCEBO and 69% and 52% for patients receiving PAdriaCEBO (P = .05, P = .12, respectively). Overall survival was significantly better with PMitCEBO than PAdriaCEBO (P = .0067). However, relapse-free survival was not significantly different (P = .16). At 4 years, 28% of PAdriaCEBO patients and 50% of PMitCEBO patients were alive (P = .0001). Ann Arbor stage III/IV, World Health Organization performance status 2-4, and elevated lactate dehydrogenase negatively influenced overall survival from diagnosis. In conclusion, the PMitCEBO 8-week combination chemotherapy regimen offers high response rates, durable remissions, and acceptable toxicity in elderly patients with HGL.