Optimal Management of Methotrexate Intoxication in a Child with Osteosarcoma

Author:

Peyriere Hélène1,Cociglio Marylène2,Margueritte Geneviève3,Vallat Catherine4,Blayac Jean-Pierre5,Hillaire-Buys Dominique6

Affiliation:

1. Hélène Peyriere PharmD PhD, Lecturer in Clinical Pharmacy, Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital, Montpellier, France

2. Marylène Cociglio PharmD PhD, Lecturer in Clinical Pharmacology, Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital

3. Geneviève Margueritte MD, Physician, Department of Pediatric Oncology, Arnaud de Villeneuve Hospital, Montpellier

4. Catherine Vallat PhD, Biologist, Laboratory of Biochemistry, Saint-Eloi Hospital, Montpellier

5. Jean-Pierre Blayac MD PhD, Professor in Clinical Pharmacology, Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital

6. Dominique Hillaire-Buys MD PhD, Lecturer in Clinical Pharmacology, Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital

Abstract

OBJECTIVE To describe the time course and management of methotrexate (MTX) toxicity in a 14-year-old Hispanic boy with osteosarcoma treated with high-dose MTX. CASE SUMMARY During the sixth cycle of high-dose MTX, severe intoxication was observed with high MTX plasma concentrations, acute renal failure, and hepatitis, followed by mucositis and moderate myelosuppression. Intensification of urine alkalinization and increased leucovorin dosages did not decrease plasma concentrations of MTX or prevent systemic toxicities. Carboxypeptidase G2 and aminophylline were thus administered as a second-intention rescue strategy. Within 2 weeks, a recovery of clinical symptoms and normalization of the biological abnormalities were observed. Limb salvage surgery was performed, which permitted classifying the patient as an MTX high-responder. Thereafter, MTX was successfully resumed, leading to clinical recovery of the patient. Concomitantly, homocysteine plasma levels, a marker of the pharmacodynamic effect of MTX, were measured. During the intoxication, homocysteine plasma levels were significantly increased, parallel to the excessive MTX plasma concentrations observed. DISCUSSION According to the excessive MTX levels measured in this patient, along with the observed clinical (mucositis) and biological (hepatitis, renal injury) adverse effects, we suggest that MTX may be a cause of these complications. Use of the Naranjo probability scale indicated a probable relationship between the complications and MTX. CONCLUSIONS This observation shows that severe complications observed during one cycle of high-dose MTX is not predictive of the tolerability of further courses. Optimal management of such complications, using specific therapeutic intervention, may be considered.

Publisher

SAGE Publications

Subject

Pharmacology (medical)

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