Severe thrombocytopenia after the first cycle of temozolomide: Who is at risk?

13019 Background: Temozolomide (TMZ) is an oral alkylating agent that has significantly improved survival of patients with glioblastoma multiforme (GBM). However, sporadic patients develop severe hematological toxicity very early, even after the first exposure to TMZ. Methods: By chart review, we identified 11 patients out of more than 300 patients treated with TMZ with the 200mg/m2 on days 1–5 regimen and 6 patients of near 200 treated with the concomitant regimen of 75 mg/m2 and radiation, who developed severe hematological toxicities (HT) after the first cycle of TMZ. The patients were 9 women and 8 men, aged 32 to 77. We checked concomitant medications (antiepileptic treatment, low molecular heparins, steroids etc.) and controlled other patient characteristics in order to detect common features. Results: All 17 patients were chemotherapy naïve before TMZ treatment. None was frail or presented with impairments of hepatic or renal function. The blood count nadir occurred mostly from day 21 to day 28 (range 11–43) and recovered usually within 2 weeks. Thrombocytopenia lasted in median for 7.5 weeks. The management of thrombocytopenia necessitated hospitalization for more than a week in all patients. Two patients developed febrile neutropenia concomitantly (one fatal). One patient did not recover from the haematological toxicity and required substitution with thrombocytes (36 units) and red cells (20 units) until week 42 when he died from progressive disease. Sixteen patients were substitutied with thrombocytes, some also red cells (n=6) and G-CSF (n=12). 10/17 patients were under antiepileptic prevention with enzyme inducing anti-epileptic drugs and 14 had thrombosis prophylaxis with low molecular weight heparin 9 patients had both. Conclusions: Our findings indicate that close meshed blood controls after the first treatment cycle with TMZ identifies the rare patients who develop early severe HT. Under treatment with TMZ, antiepileptic prophylaxis with enzyme inducing drugs should only be maintained if other AEDs are contraindicated, as thromboembolic prophylaxis with low molecular weight heparin postoperatively remains indispensable in high-grade glioma patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Mundipharma, Novartis, Schering-Plough