Long-term survival in glioblastoma patients treated with dopamine agonists: A report of two cases and implications for drug repurposing.

Background: Glioblastoma (GBM) remains the most lethal primary brain tumor, with a median survival of 15 months and a 10-year survival rate of <1%. While current research into the dopaminergic system has largely focused on dopamine receptor antagonists, we aimed to investigate the potential therapeutic benefit of dopamine agonists (dopamine receptor D2) through the observation of incidental "super-survivors." Case Description: We report two cases of adult GBM patients who received concurrent treatment with dopamine agonists for unrelated comorbidities. The first patient, treated with the ergot derivative bromocriptine for a prolactinoma, presented with multifocal disease and underwent subtotal resection. Despite developing a recurrence, he remains alive and progression-free for >11 years after diagnosis. The second patient, a 70-year-old male with Parkinson's disease treated with the non-ergot dopamine agonist pramipexole and with Sinemet, which increases the amount of available dopamine. He had a low Karnofsky Performance Score and received minimal adjuvant therapy. Despite these poor prognostic factors, he achieved a progression-free survival of 15 months and did not succumb to tumor progression. Conclusion: These observational cases suggest a hypothetical association between dopamine agonist therapy and improved survival outcomes in GBM, challenging the current paradigm that favors receptor antagonism. Given the safety, low cost, and blood-brain barrier penetrance of these Food and Drug Administration-approved drugs, we propose that dopamine agonists warrant further investigation as repurposed adjuvant agents in GBM treatment.