Adjuvant chemotherapy after severe myelotoxicity during chemoradiation phase in malignant gliomas. Is it feasibile? Results from AINO study (Italian Association for Neuro-Oncology)

Background: Malignant gliomas (MG) are aggressive brain tumours in adults. The standard of care is concurrent radiation plus temozolomide (TMZ) [chemo-radiotherapy (CRT)] followed by TMZ maintenance up to 6 months. TMZ is considered to have a low toxicity profile, but several studies reported occurrence of severe myelosuppression, especially during the concomitant phase. Toxicity may be prolonged, thus treatment should be discontinued.

Purpose: To evaluate the risk of recurrente myelotoxicity during adjuvant chemotherapy (CT) in patients who recovered from severe myelotoxicity during CRT.

Methods: We retrospectively collected data on patients with MG who developed and recovered from severe myelotoxicity during CRT from eight Italian neuro-oncology centers.

Results: We included 87 patients. Histology was Glioblastoma (GBM) in 78 patients (89.7%); 60% of patients were female. After myelotoxicity recovery, 54 (62%) received treatment. The majority of them (82%, n = 44) received adjuvant TMZ and 18% (n = 10) others treatments. Out of 44 patients who received adjuvant TMZ, 34% experienced the re-occurrence of grade 3-4 myelotoxicity which required permanent CT discontinuation in 6 (13%) cases. Patients who received TMZ or other treatments had longer overall (OS) (adjusted HR 0.46, p = 0.008) and progression free survival (PFS) (adjusted HR 0.57, p = 0.034) than those who remained untreated.

Conclusion: Our study suggests that after severe myelotoxicity the majority of patients received treatment, particularly with TMZ. Only a fraction of patients experienced toxicity recurrence, suggesting that TMZ is well tolerated and had an impact on PFS and OS.