Efficacy and safety of rasburicase (recombinant urate oxidase) for the prevention and treatment of hyperuricemia during induction chemotherapy of aggressive non-Hodgkin's lymphoma: results of the GRAAL1 (Groupe d'Etude des Lymphomes de l'Adulte Trial on Rasburicase Activity in Adult Lymphoma) study.

Abstract

PURPOSE:

Hyperuricemia and tumor lysis syndrome are well-known complications during induction treatment of aggressive non-Hodgkin's lymphomas (NHLs). Usual prophylaxis and treatment of hyperuricemia consist of hydration, alkalinization, and administration of allopurinol. This study was designed to evaluate the efficacy and the safety of rasburicase (recombinant urate oxidase) in adult patients with aggressive NHL during their first cycle of chemotherapy.

PATIENTS AND METHODS:

A total of 100 patients from Groupe d'Etude des Lymphomes de l'Adulte centers, with diffuse large B-cell lymphoma (n = 79); anaplastic large-cell lymphoma (n = 6); peripheral T-cell lymphoma (n = 8); transformation of indolent lymphoma (n = 5); Burkitt's lymphoma (n = 1); and lymphoblastic lymphoma (n = 1) were enrolled from May 2001 to June 2002. Before chemotherapy, 66% of patients had elevated lactate dehydrogenase (LDH), including 28% with LDH above 1,000 U/mL. Eleven percent of patients were hyperuricemic (uric acid [UA] > 450 mmol/L or > 7.56 mg/dL). Rasburicase 0.20 mg/kg/d intravenously for 3 to 7 days was started the day before or at day 1 of chemotherapy. UA levels were measured 4 hours after rasburicase injection, then daily during treatment.

RESULTS:

All patients responded to rasburicase, as defined by normalization of UA levels maintained during chemotherapy. The control of UA was obtained within 4 hours after the first injection of the drug. Creatinine levels and other metabolites were also controlled with the administration of rasburicase. No patient exhibited increased creatinine levels or required dialysis during chemotherapy.

CONCLUSION:

Rasburicase is the treatment of choice to control UA and prevent tumor lysis syndrome in adult patients with aggressive NHL.

• Authors: Bertrand Coiffier, Nicolas Mounier, Serge Bologna, Christophe Fermé, Hervé Tilly, Anne Sonet, Bernard Christian, Olivier Casasnovas, Eric Jourdan, Karim Belhadj, Raoul Herbrecht, Groupe d'Etude des Lymphomes de l'Adulte Trial on Rasburicase Activity in Adult Lymphoma
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 21 Issue 23 Pg. 4402-6 (Dec 01 2003) ISSN: 0732-183X [Print] United States
• PMID: 14581437 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article)

Chemical References

• Antineoplastic Agents
• Recombinant Proteins
• rasburicase
• Uric Acid
• Creatinine
• Urate Oxidase

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use)
• Creatinine (blood)
• Female
• Humans
• Hyperuricemia (drug therapy, etiology, prevention & control)
• Injections, Intravenous
• Lymphoma, Non-Hodgkin (drug therapy)
• Male
• Middle Aged
• Recombinant Proteins (therapeutic use)
• Remission Induction
• Safety
• Treatment Outcome
• Tumor Lysis Syndrome (drug therapy, etiology)
• Urate Oxidase (therapeutic use)
• Uric Acid (blood)