Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.
Vol 23, No 16S (June 1 Supplement), 2005: 1546
© 2005 American Society of Clinical Oncology

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Abstract

Fatal hematologic toxicity with prolonged continuous administration of temozolomide (TMZ) during radiation therapy (RT) in the treatment of newly-diagnosed glioblastoma multiforme (GBM): Report of a Phase II trial

Henry Ford Hosp, Detroit, MI; NeoPharm Inc, Lake Forest, IL

1546

Background: A Phase III trial demonstrated superior survival in GBM patients (pts) treated with postoperative RT and concomitant and adjuvant TMZ. Hematologic toxicity was acceptable; only 7% of pts experienced grade 3/4 toxicity (Stupp et al, ASCO Proc 2004, No. 2). The current phase II trial studied the same regimen. Methods: Pts age 18 with newly diagnosed histologically-proven GBM and KPS 60 with normal hematologic, hepatic and renal function were enrolled from 1/2001–10/2002. RT (60 Gy in 30 daily fractions of 2 Gy) and concomitant TMZ 75mg/m² for up to 42 days were administered. Adjuvant TMZ 200mg/m² day 1–5 every 28 days for up to 12 cycles was given following RT. Survival and toxicity were primary endpoints. Prophylactic trimethoprim-sulfamethoxazole (TMP-SMZ) 160mg/800mg 3 times weekly was given to those taking dexamethasone. Results: 16 pts were registered and all included in the analysis. The table describes survival and hematologic toxicity of all 16 pts. 3 (3/16, 19%) died from toxicity of TMZ given with RT. These are detailed in the lower part of the table. 1 pt had bone marrow (BM) biopsies (day 46 and 67) showing aplasia. Another pts day 38 BM biopsy showed 5% cellularity. Grade 3/4 thrombocytopenia preceded grade 3/4 neutropenia. Conclusions: 3/16 pts experienced fatal hematologic toxicity following daily TMZ 75mg/m² during RT. 2 pts had BM examinations; 1 had aplastic anemia, the other only 5% cellularity. Due to routine use of TMP-SMZ prophylaxis, a drug interaction with TMZ cannot be excluded as a cause of hematologic toxicity. Further investigation is warranted. Caution is advised when using this regimen.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering Schering

Abstract presentation from the 2005 ASCO Annual Meeting