Abstract |
Recombinant interferon alpha-2b (IFN-alpha2) has direct and indirect antiproliferative effects in lymphoma, and may augment cytotoxicity when combined with chemotherapy. CALGB 8691 is a randomized study of daily oral cyclophosphamide (CPA) at 100 mg/m2 with or without IFN-alpha2 at 2 x 106 IU/m2 three times per week, followed by a second randomization between IFN-alpha2 maintenance (2 x 106 IU/m2 three times weekly) versus observation in treatment-naïve patients with follicular lymphoma (FL). Five hundred eighty-one patients were randomized to either CPA (n = 293) or CPA plus IFN-alpha2 (n = 288). One hundred five responding patients were randomized to observation and 99 to maintenance IFN-alpha2. With a median follow-up of 11.5 years, the median event-free and overall survival (OS) for CPA induction alone were 2.5 years (95% CI 2.2, 3.0) and 9 years (95% CI 7.7, 10.2), compared to 2.4 years (95% CI 2.1, 3.1) and 8.4 years (95% CI 7.5, 11.1) for the combination arm (p = NS). Patients with a partial response (PR) and randomized to observation had the worst outcome (event-free survival (EFS) 1.8 years versus 3.9 years; p = 0.002). Patients with a PR randomized to IFN-alpha2 had a similar EFS to compared to patients with complete response (CR), but this did not translate into a survival advantage. Myelosuppression was increased in IFN-alpha2-containing arms. Despite the small benefit in EFS in patients with PR randomized to IFN-alpha2 maintenance, we conclude that the addition of low dose IFN-alpha2 did not significantly improve the response rate, duration of response, event-free, or OS obtained with single-agent daily oral CPA in patients with previously untreated FL.
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Authors | S M Smith, J Johnson, B D Cheson, G Canellos, G Petroni, M Oken, D Duggan, D Hurd, J P Gockerman, B Parker, J Prchal, B A Peterson, Cancer and Leukemia Group B, Eastern Cooperative Oncology Group |
Journal | Leukemia & lymphoma
(Leuk Lymphoma)
Vol. 50
Issue 10
Pg. 1606-17
(Oct 2009)
ISSN: 1029-2403 [Electronic] United States |
PMID | 19626540
(Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
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Chemical References |
- Antigens, CD20
- Antineoplastic Agents, Alkylating
- Immunologic Factors
- Interferon alpha-2
- Interferon-alpha
- Recombinant Proteins
- Cyclophosphamide
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Antigens, CD20
(biosynthesis, immunology)
- Antineoplastic Agents, Alkylating
(administration & dosage, adverse effects, therapeutic use)
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects, therapeutic use)
- Combined Modality Therapy
- Cyclophosphamide
(administration & dosage, adverse effects, therapeutic use)
- Drug Synergism
- Female
- Follow-Up Studies
- Humans
- Immunologic Factors
(administration & dosage, adverse effects)
- Interferon alpha-2
- Interferon-alpha
(administration & dosage, adverse effects)
- Lymphoma, Follicular
(drug therapy)
- Male
- Middle Aged
- Neoplasms, Second Primary
(chemically induced)
- Recombinant Proteins
- Survival Analysis
- Treatment Failure
- Young Adult
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