Unusual adverse drug reactions in high grade glioma patients treated with temozolomide

BACKGROUND: Temozolomide (TMZ) is an oral alkylating agent which is the most common chemotherapy used in neuro-oncology and is typically well tolerated. The most common adverse events include fatigue, nausea, vomiting, headache, and constipation and most serious being myelosuppression. Review of the literature uncovered rare reports of acute reactions to TMZ, typically limited to skin rashes and eruptions. METHODS: The Neuro-Oncology Branch has initiated a natural history study in which clinical course and current status are interrogated. A retrospective analysis of this protocol was performed, and cases of unusual reactions to TMZ were identified. RESULTS: This study included 144 patients, with the majority being males (65%) with glioblastoma (31%) and a mean age of 47. Ninety (62%) received TMZ with concurrent radiation or in the adjuvant setting, of which 3 patients (4%) developed unusual symptoms within hours of taking TMZ. A 70-year-old male developed severe rigors, joint pains, and fever within 1 hour of ingesting TMZ, prescribed in the adjuvant setting. Infectious work-up was negative and re-challenge with TMZ produced the same syndrome. A 47-year-old female on C2D2 of TMZ with nivolumab in the adjuvant setting, developed chills, joint pain, and a fever that resolved with drug cessation. A rechallenge with TMZ resulted in the same symptoms within two hours of ingestion. A 24-year-old female developed severe burning paresthesias on C4D2 of TMZ with nivolumab which resolved with lorazepam and cessation of TMZ. Re-challenge with TMZ resulted in recurrence of burning paresthesias within 1-2 hours of ingestion. In all 3 cases, symptoms resolved with stopping TMZ, and alternative therapeutic strategies were initiated. CONCLUSION: Awareness of these unusual reactions to TMZ is important in clinical practice as the prompt recognition and discontinuation of the drug improves patient safety and may avoid the use of unnecessary diagnostic procedures.