Is oxaloacetate effective for treating glioblastoma?

Oxaloacetate is Not Recommended for Treating Glioblastoma

Oxaloacetate is not currently recommended as a treatment for glioblastoma as it is not included in any established clinical guidelines for glioma management and lacks sufficient high-quality clinical evidence to support its use.

Standard of Care Treatment for Glioblastoma

The established standard of care for glioblastoma consists of:

1. Surgical Management

   • Maximal safe surgical resection when technically feasible 1
   • Transfer to a specialized neuro-oncology center for evaluation and surgical management 2
   • Biopsy if optimal resection is not possible 1

2. Radiotherapy

   • External-beam radiotherapy (60 Gy total dose) delivered in daily fractions of 1.8-2 Gy over 6 weeks 1
   • Hypofractionated regimens (e.g., 40 Gy in 15 fractions) for elderly patients or those with poor performance status 1

3. Chemotherapy

   • Concomitant and adjuvant temozolomide, which has demonstrated significant improvement in median and 2-year survival in randomized trials 1
   • Consideration of MGMT promoter methylation status to predict benefit from temozolomide 1
   • Nitrosourea-based chemotherapy (e.g., carmustine, lomustine) as alternative options 1
   • BCNU wafers (carmustine implants) as an option in selected cases 1

Evidence Regarding Oxaloacetate

The evidence for oxaloacetate in glioblastoma treatment is limited:

• Preclinical studies suggest oxaloacetate may work by:

  • Inhibiting lactate dehydrogenase A (LDHA) in cancer cells, potentially reversing the Warburg effect 3
  • Acting as a blood glutamate scavenger, which may reduce tumor growth 4
  • Enhancing the efficacy of standard treatments by improving neuronal cell bioenergetics 3

• Animal studies have shown:

  • Smaller tumor volume and prolonged survival in rats and mice with brain-implanted gliomas when treated with oxaloacetate 4
  • Enhanced effects when combined with temozolomide in mice 4

However, there are critical limitations:

• No human clinical trials demonstrating efficacy
• No inclusion in any major clinical guidelines for glioblastoma management
• Absence from ESMO, NCCN, or other authoritative treatment recommendations 1, 2

Treatment Recommendations for Recurrent Disease

For recurrent glioblastoma, established options include:

• Repeat surgery when feasible 1
• Reirradiation using modern high-precision techniques 1
• Systemic chemotherapy options:
  • Nitrosoureas (lomustine, carmustine) 1
  • Temozolomide rechallenge in selected patients 1
  • Bevacizumab (approved in the USA, Canada, Switzerland, but not EU) 1, 5
• Enrollment in clinical trials 5

Practical Considerations

When managing glioblastoma patients:

• Treatment decisions should be made by a multidisciplinary neuro-oncology team 1, 2
• Prognostic factors to consider include age, performance status, extent of resection, and molecular markers 2
• Regular follow-up with MRI surveillance (typically every 3 months initially) 1, 2
• Appropriate management of complications including seizures, thromboembolism, and cerebral edema 1, 2

Conclusion

While oxaloacetate shows some promise in preclinical studies, particularly when combined with temozolomide 4, it remains an experimental approach without sufficient clinical evidence to recommend its use outside of clinical trials. Patients with glioblastoma should receive the established standard of care treatments outlined in current clinical guidelines, with consideration for clinical trial enrollment when appropriate.