Is mebendazole effective for treating glioblastoma?

Mebendazole for Glioblastoma: Current Evidence and Recommendations

Mebendazole is not currently recommended as a standard treatment for glioblastoma as there is insufficient clinical evidence to support its use outside of clinical trials. While preclinical studies show promise, there are only limited phase 1 clinical trials available, and mebendazole is not included in any major treatment guidelines for glioblastoma.

Current Standard of Care for Glioblastoma

The established standard of care for newly diagnosed glioblastoma includes:

• Maximal safe surgical resection when feasible
• Adjuvant radiation therapy with concurrent and adjuvant temozolomide for patients up to 70 years of age with good performance status 1
• For elderly patients (≥70 years), hypofractionated radiotherapy is recommended, with the addition of temozolomide particularly beneficial for those with MGMT promoter methylation 1

Evidence for Mebendazole in Glioblastoma

Preclinical Evidence

• In preclinical models, mebendazole demonstrated cytotoxicity against glioblastoma cell lines with half-maximal inhibitory concentrations of 0.1-0.3 μM 2
• Mebendazole was shown to disrupt microtubule formation in GBM cells and extended mean survival by up to 63% in mouse glioma models 2

Clinical Evidence

• A phase 1 study (Reverse swing-M) evaluated mebendazole in recurrent high-grade glioma in combination with re-irradiation plus temozolomide, CCNU, or temozolomide alone 3
• Another phase 1 trial in 24 patients with newly diagnosed high-grade gliomas combined mebendazole with adjuvant temozolomide, establishing doses up to 200 mg/kg/day with acceptable toxicity 4
• The most common adverse events included anemia, nausea, fatigue, and elevated liver enzymes 3, 4

Limitations of Current Evidence

1. Limited Clinical Data: Only phase 1 trials have been completed, focusing primarily on safety and dosing rather than efficacy
2. Absence from Guidelines: Major treatment guidelines from ASCO, NCCN, and EANO do not include mebendazole as a recommended therapy 1
3. No Comparative Efficacy: No randomized controlled trials have compared mebendazole to standard treatments

Potential Mechanisms and Combinations

Recent research suggests that:

• Mebendazole induces autophagy in glioblastoma cells
• Combining mebendazole with autophagy inhibitors like chloroquine may enhance its anti-tumor effects 5
• Triple combination of mebendazole, temozolomide, and chloroquine showed enhanced anti-proliferative effects in preclinical studies 5

Clinical Considerations

For patients interested in mebendazole:

• Participation in clinical trials should be the primary recommendation 1
• The established dose from phase 1 trials is 1600 mg TDS with temozolomide and temozolomide-radiation combination, while 800 mg TDS is recommended with CCNU 3
• Liver function monitoring is essential as grade 3 elevations in ALT/AST were observed in some patients 4

Conclusion

While mebendazole shows promising activity in preclinical studies and early phase clinical trials, it has not yet demonstrated sufficient efficacy in clinical settings to be recommended as standard therapy for glioblastoma. The current standard of care with maximal safe resection followed by radiation therapy and temozolomide remains the established approach with proven survival benefit. Patients interested in mebendazole treatment should be encouraged to participate in clinical trials where its efficacy can be properly evaluated.