Temozolomide desensitization followed by metronomic dosing in patients with hypersensitivity

• Published in: Cancer chemotherapy and pharmacology 2020-09, Vol.86 (3), p.375-382
• Main Authors: Neth, Bryan J., Ruff, Michael W., Uhm, Joon H., Johnson, Derek R., Divekar, Rohit D., Maddox, Daniel E.
• Format: Article
• Language: English
• Subjects: Administration, Metronomic; Adult; Aged; Antineoplastic Agents, Alkylating - administration & dosage; Brain Neoplasms - drug therapy; Brain Neoplasms - immunology; Brain Neoplasms - pathology; Cancer Research; Chemotherapy; Chemotherapy, Adjuvant; Desensitization; Desensitization, Immunologic - methods; Disease control; Female; Follow-Up Studies; Glioma; Glioma - drug therapy; Glioma - immunology; Glioma - pathology; Humans; Hypersensitivity; Hypersensitivity - drug therapy; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original Article; Patients; Pharmacology/Toxicology; Prognosis; Retrospective Studies; Survival; Survival Rate; Temozolomide; Temozolomide - administration & dosage
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-020-04123-y

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.