Temozolomide desensitization followed by metronomic dosing in patients with hypersensitivity
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ORIGINAL ARTICLE
Temozolomide desensitization followed by metronomic dosing in patients with hypersensitivity Bryan J. Neth1 · Michael W. Ruff1 · Joon H. Uhm1 · Derek R. Johnson1,2 · Rohit D. Divekar3 · Daniel E. Maddox3 Received: 6 May 2020 / Accepted: 3 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose Temozolomide is the most effective chemotherapy for malignant glioma. Hypersensitivity requiring interruption of therapy may significantly impact patient survival. We have successfully employed temozolomide desensitization followed by metronomic dosing of temozolomide. Our purpose was to report patient characteristics and outcomes in patients with glioma (Grade 2–4) and temozolomide hypersensitivity managed by desensitization and metronomic dosing. Methods We performed an observational study of 15 patients at Mayo Clinic (Rochester) with a diagnosis of glioma who underwent temozolomide desensitization with subsequent metronomic dosing from May 2012 to January 2017. We calculated overall and progression-free survival using the Kaplan–Meier method, and log-rank analyses to assess for differences in survival by WHO Grade or treatment initiation. Results Median age at time of desensitization was 49.3 years (26.8–64.7 years). Median follow-up after desensitization was 35.5 months. One patient (6.7%) was unable to resume temozolomide due to recurrent allergy. The median time from first desensitization to discontinuation of metronomic temozolomide was 4.2 months (0–15.2 months). Median OS and PFS for the whole sample were 181.7 months and 44.9 months. For Grade 4, OS was 100% at 1 year, 40% at 3 years, 20% at 5 years; and PFS was 60% at 1 year, 40% at 3 years, and 20% at 5 years. Conclusion Our results suggest that rapid-desensitization followed by metronomic temozolomide should be considered in patients with glioma who experience hypersensitivity. This strategy provides comparable outcomes to therapy with standard protocols, with the majority of patients able to tolerate temozolomide after desensitization with favorable disease control. Keywords Temozolomide hypersensitivity · Glioma · Desensitization · Metronomic dosing · Survival
Introduction Temozolomide (TMZ) is an alkylating chemotherapeutic used in the treatment of malignant glioma. TMZ is cytotoxic through alkylation of guanine nucleotides after nonenzymatic conversation to its active form (5-(3-methyltriazen-1-yl)imidazole-4-carboxamide or MTIC) [1–3]. Per the Stupp protocol, TMZ is administered at 75 mg/m2/day for 42 days concurrently with radiotherapy followed by adjuvant
* Bryan J. Neth [email protected] 1
Department of Neurology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905, USA
2
Department of Radiology, Mayo Clinic, Rochester, MN, USA
3
Division of Allergic Diseases, Department of Medicine, Mayo Clinic, Rochester, MN, USA
therapy for 6 cycles at higher doses (150–200 mg/m2/day) [1, 2]. The most common adverse effects associated with TMZ include alopecia, fatigue, rash, nausea, vomiting,
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