Severe thrombocytopenia from temozolomide (TMZ) in newly diagnosed patients with high-grade gliomas.

5283 BACKGROUND: Standard therapy for patients with newly diagnosed glioblastoma multiforme now includes temozolomide (TMZ) (75 mg/m2/day) administered with radiation therapy (RT) for 6 weeks, followed by 6 cycles of adjuvant TMZ (150-200 mg/m2/day for 5 days during each 28-day cycle). In the phase III clinical trial of this regimen (Stupp et al., NEJM 2005), thrombocytopenia was reported to be modest (12% grade 3/4) over the 8.5 months of planned treatment, and most cases (73%) of grade 3/4 thrombocytopenia developed during the monthly adjuvant cycles of TMZ. In this study, we further characterize the thrombocytopenia associated with this therapy. METHODS: A retrospective chart review was conducted of 52 consecutive patients with newly diagnosed high-grade gliomas treated with this regimen at The Johns Hopkins Hospital between June 2004 and October 2005. RESULTS: The median age of these patients was 57 years, and 54% were male. Almost all patients received corticosteroids, anticonvulsants, and trimethoprim-sulfamethoxazole. Histology included glioblastoma multiforme (73%), anaplastic astrocytoma (21%), and anaplastic oligodendroglioma (6%). Grade 3/4 thrombocytopenia was seen in 10 patients (19%). Five patients (10%) required platelet transfusions (range 1-59 transfusions). Two patients (4%) never recovered platelet counts, requiring biweekly platelet transfusions for over 6 months. In these patients, bone marrow evaluation demonstrated absent megakaryocytes. Therapy was discontinued in 9 patients (17%) because of thrombocytopenia. The median time to onset of grade 3/4 thrombocytopenia was 52 days, and the median duration was 32 days (range 1-217 days). Most cases (80%) of grade 3/4 thrombocytopenia developed during the daily TMZ and RT segment of therapy. Grade 3/4 thrombocytopenia occurred in 25% of women and 14% of men on this regimen and was not associated with age, renal or hepatic function, body surface area, use of anticonvulsants or antibiotics, or tumor histology. Grade 3/4 neutropenia (10%) and anemia (10%) had much less impact on the clinical course of these patients. CONCLUSIONS: This treatment regimen can result in severe and potentially irreversible thrombocytopenia. The factors that predispose certain patients to this toxicity have yet to be determined.