Complications of a temozolomide overdose: a case report
- 175 Downloads
Purpose and background
This is a report of a 53 year-old man with a glioblastoma multiforme (GBM) treated with an excessive dose of temozolomide (TMZ).
This is a single case review of all clinically relevant records. O 6-methylguanine-DNA methyltransferase activity was determined by a biochemical assay.
Following conventional radiotherapy (RT) without concurrent chemotherapy, the patient received 5,500 mg of TMZ over 2 days. At the standard dose of 200 mg/m2/day his total 5-day dose should have been 1,940 mg. Acutely he had nausea, vomiting and diarrhea for 2 days which cleared. The dominant severe toxicity was pancytopenia between one and four weeks after TMZ which was complicated by secondary infections that were successfully managed. Transient transaminitis occurred but there were no significant pulmonary, renal or other systemic toxicities. His progression free survival was 22 months and overall survival 24 months.
His outcome suggests that TMZ may prove to be a good agent for dose-escalation trials with hematopoietic stem cell rescue.
KeywordsGlioblastoma multiforme Temozolomide Overdose Toxicity
Unable to display preview. Download preview PDF.
- 2.Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003PubMedCrossRefGoogle Scholar
- 9.Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996PubMedCrossRefGoogle Scholar
- 11.Kokkinakis DM, Bocangel DB, Schold SC, Moschel RC, Pegg AE (2001) Thresholds of O 6-alkylguanine-DNA alkyltransferase which confer significant resistance of human glial tumor xenografts to treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea or temozolomide. Clin Cancer Res 7:421–428PubMedGoogle Scholar
- 14.Durando X, Lemaire JJ, Tortochaux J, Van-Praagh I, Kwiatkowski F, Vincent C, Bailly C, Verrelle P, Irthum B, Chazal J, Bay JO (2003) High-dose BCNU followed by autologous hematopoietic stem cell transplantation in supratentorial high-grade malignant gliomas: a retrospective analysis of 114 patients. Bone Marrow Transplant 31:559–564PubMedCrossRefGoogle Scholar
- 18.Quinn JA, Desjardins A, Weingart J, Brem H, Dolan ME, Delaney SM, Vredenburgh J, Rich J, Friedman AH, Reardon DA, Sampson JH, Pegg AE, Moschel RC, Birch R, McLendon RE, Provenzale JM, Gururangan S, Dancey JE, Maxwell J, Tourt-Uhlig S, Herndon JE II, Bigner DD,␣Friedman HS (2005) Phase I trial of temozolomide plus O 6-benzylguanine for patients with recurrent or progressive malignant glioma. J Clin Oncol 23:7178–7187PubMedCrossRefGoogle Scholar