Sage Journals: Discover world-class research

Abstract

Purpose. To describe the successful use of glucar- pidase (carboxypeptidase G2) in the treatment of high-dose methotrexate-induced nephrotoxicity in a patient with osteosarcoma.

Summary. A 12-year-old female patient who had been diagnosed with low-grade right mandibular osteosarcoma was started on a protocol of cisplatin plus doxorubicin alternating with high-dose metho- trexate. Following her first dose of methotrexte, she developed acute renal failure and higher than expected 24h methotrexate level of 478μM/L. High-dose leucovorin rescue was started with vigorous hydra- tion and urine alkalinization together with two sessions of hemodialysis. Because her methotrexate level was persistently high, the investigational drug glucarpidase was administered. Methotrexate leveldropped from 65 to 16.3 μM/L after a single dose of glucarpidase measured by fluorescence polarization immunoassay. Leucovorin and urine alkalinization were continued until day 17 when the patient’s kidney function normalized and methotrexate level reached 0.05 μM/L. The patient tolerated glucarpidase well without any significant adverse events.

Conclusion. Glucarpidase is a safe and effective agent in the management of high-dose methotrexate-induced nephrotoxicity and delayed methotrexate elimination. J Oncol Pharm Practice (2011) 17: 136—140.

Keywords

glucarpidase carboxypeptidase G2 methotrexate nephrotoxicity osteosarcoma

Get full access to this article

View all access options for this article.

References

Van Dalen EC , de Camargo B. Methotrexate for high-grade osteosarcoma in children and young adults. Cochrane Database Syst Rev. 2009;21;(1):CD006325.

DeAngelis LM , Hormigo A. Treatment of primary central nervous system lymphoma. Semin Oncol 2004; 31: 684-92.

Bleyer WA Methotrexate: clinical pharmacology, current status and therapeutic guidelines . Cancer Treat Rev 1977; 4: 87-101.

Walling J. From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates. Invest New Drugs 2006; 24(1): 37-77.

Kummar S. , Noronha V. , Chu E. Antimetabolites. In: DeVita VT , Hellman S , Rosenberg SA. eds. Cancer principles and practice of oncology, seventh edn. Philadelphia: Lippincott Williams & Wilkins, 2005: 358-374.

Messmann R. , Allegra C. Antifolates. In: Chabner B , Longo D. eds. Cancer chemotherapy and biotherapy. Philadelphia: Lippincott Williams & Wilkins, 2001: 139-84.

Widemann BC , Adamson PC Understanding and managing methotrexate nephrotoxicity. The Oncologist 2006; 11: 694-703.

Buchen S. , Ngampolo D. , Melton RG , Hasan C. , Zoubek A. , Henze G. et al. Carboxypeptidase G2 rescue in patients with methotrexate intoxication and renal failure. Br J Cancer 2005; 92: 480-87.

Glucarpidase supply information. Available at: www.protherics.com (accessed June 28, 2009).

10.

Suzuki K. , Doki K. , Homma M. , Tamaki H. , Horis S. , Ohtani et al. Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapy. Br J Clin Pharmacol 2009; 67(1): 44-49.

11.

Widemann BC , Balis FM , Kempf-Bielack B. , Bielack S. , Pratt CB , Ferrari S. et al. High-dose methotrexate-induced nephrotoxicity in patients with osteosarcoma. Cancer 2004; 100: 2222-32.

12.

Green MR , Chamberlain MC Renal dysfunction during and after high-dose methotrexate. Cancer Chemother Pharmacol 2009; 63: 599-604.

13.

Crews KR , Liu T. , Rodriguez-Galindo C. , Tan M. , Meyer WH , Panetta JC et al. High-dose methotrexate pharmacokinetics and outcome of children and young adults with osteosarcoma. Cancer 2004; 100: 1724-33.

14.

Flombaum CD , Meyers PA High-dose leucovorin as sole therapy for methotrexate toxicity. J Clin Oncol 1999; 17: 1589-94.

15.

Frei III E. , Blum RH , Pitman SW , Kirkwood JM , Henderson IC , Skarin AT et al. High dose methotrexate with leucovorin rescue: rationale and spectrum of antitumor activity. Am J Med 1980; 68: 370-76.

16.

Van den Bongard HJ , Mathjt RA , Boogerd W. , Schornagel JH , Soesan M. , Schellens JH et al. Successful rescue with leucovorin and thymidine in a patient with high-dose methotrexate induced acute renal failure . Cancer Chemother Pharmacol 2001; 47(6): 537-40.

17.

Relling MV , Stapleton FB , Ochs J. , Jones DP , Meyer W. , Wainer IW et al. Removal of methotrexate, leucovorin, and their metabolites by combined hemodialysis and hemoperfusion. Cancer 1988 ; 62: 884-88.

18.

Schwartz S. , Borner K. , Muller K. , Martus P. , Fischer L. , Korfel A. et al. Glucarpidase (Carboxypeptidase G2) Intervention in adult and elderly cancer patients with renal dysfunction and delayed methotrexate elimination after high-dose methotrexate therapy. The Oncologist 2007; 12: 1299-308.

19.

Snyder RL Resumption of high-dose methotrexate after methotrexate-induced nephrotoxicity and carboxypeptidase G2 use. Am J Health-Syst Pharm 2007; 64: 1163-69.

20.

Estève MA , Devictor-Pierre B. , Galy G. , André N. , Coze C. , Lacarelle B. et al. Severe acute toxicity associated with high-dose methotrexate (MTX) therapy: use of therapeutic drug monitoring and test-dose to guide carboxypeptidase G2 rescue and MTX continuation. Eur J Clin Pharmacol 2007; 63: 39-42.

21.

Evans WE , Crom WR , Abromowitch M. , Dodge R. , Look AT , Bowman WP et al. Clinical pharmacodynamics of high-dose methotrexate in acute lymphocytic leukemia. N Engl J Med 1986; 314: 471-77.

22.

Kawai A. , Healey JH , Boland PJ , Lin PP , Huvos AG , Meyers PA Prognostic factors for patients with sarcomas of the pelvic bones. Cancer 1998; 82(5): 851-59.

Glucarpidase rescue in a patient with high-dose methotrexate-induced nephrotoxicity

Abstract

Keywords

Get full access to this article

References