Sequential hydroxyurea-cytarabine chemotherapy for refractory non-Hodgkin's lymphoma.

Abstract

In experimental systems, hydroxyurea (HU) and cytarabine (ara-C) produce synergistic cytotoxicity to murine and human leukemia cells due to both cytokinetic and biochemical interactions that tend to enhance the effectiveness of ara-C. Therefore, we began a phase II trial of the combination of HU and ara-C to determine the efficacy and toxicity of this combination in treatment of patients with refractory non-Hodgkin's lymphoma. Chemotherapy began with HU 500 mg administered orally every six hours for four doses. Twelve hours following the fourth HU dose, ara-C 100 mg/m2/d was administered by continuous intravenous (IV) infusion for three days. Concomitantly with the three-day ara-C infusion, patients again received HU 500 mg orally every four hours. Cycles of therapy were repeated every 28 days. Twenty-five patients ranging in age from 26 to 70 years were enrolled in the study. Of 21 patients evaluable for response, nine (43%) obtained complete (CR) or partial remissions (PR). Most responding patients had either large-cell or cutaneous T cell lymphoma, and all but two had a performance status of 0 to 1 at entry in the study. The median survival for all responding patients was 13 months compared with 2.5 months for nonresponders. Patients obtaining a CR had a median survival of 27.5 months, and two of the four CRs remain alive and in remission at 10+ and 30+ months from achievement of CR status. The primary toxic effect of this regimen was bone marrow suppression. The median WBC nadir was 2,200 cells/microL, and the median platelet nadir was 80,000/microL. Other toxicities included mild nausea and vomiting and diffuse maculopapular rash. This biochemically rational approach to enhancing ara-C activity may have significant clinical utility and should be further explored in treatment of patients with large-cell and cutaneous T cell lymphomas.

• Authors: R L Schilsky, S F Williams, J E Ultmann, S Watson
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 5 Issue 3 Pg. 419-25 (Mar 1987) ISSN: 0732-183X [Print] United States
• PMID: 3819808 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cytarabine
• Hydroxyurea

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Cytarabine (administration & dosage)
• Drug Evaluation
• Female
• Humans
• Hydroxyurea (administration & dosage)
• Lymphoma, Non-Hodgkin (drug therapy, pathology)
• Male
• Middle Aged