Addition of 4 Older Drugs Could Improve Bevacizumab's Effect in Glioblastoma

Bevacizumab, an anti—vascular endothelial growth factor (anti-VEGF) treatment for which 1 biosimilar has been approved to date, has been shown to improve quality of life for patients with glioblastoma—and to delay disease progression—but has not prolonged patients’ overall survival.

However, recent research suggests that using 4 older drugs together with bevacizumab could provide a more effective treatment protocol. Writing in Medical Sciences, Richard E. Kast, MD, describes the current research supporting this regimen.

The drugs in question are apremilast, which treats psoriasis; dapsone, an antibiotic that treats Hansen disease; zonisamide, which treats seizures; and telmisartan, which treats hypertension.

• Apremilast is a selective phosphodiesterase 4 inhibitor, and such inhibitors have been shown to augment bevacizumab, exert anti-glioma growth effects, and lower the synthesis of inflammation-related cytokines. Because the cytokines targeted by this drug are also known to participate in glioblastoma growth, “we might expect benefits from apremilast on this basis alone.”
• Dapasone has been shown to reduce rash mediated by VEGF-containing neutrophils, and is expected to augment bevacizumab by reducing neutrophil-borne VEGF.
• Zonisamide inhibits carbonic anhydrase, which is present in glioblastomas. Similar drugs have also been shown to increase the pH of intracellular glioblastoma.
• Telmisartan is an angiotensin receptor blocking drug that is uniquely lipophilic, has an affinity to the angiotensin 2 type 1 receptor, and inhibits peroxisome proliferator-activated receptor-γ. Promising results for such drugs have been found in non-squamous, non—small cell lung cancer that was treated with or without bevacizumab, notably.

Using these drugs in combination with bevacizumab is expected to lower intracranial pressure, allow for steroid-sparing treatment, enhance bevacizumab’s effects, provide synergy with temozolomide, exert anti-glioma effects, and have low risk of adverse events.

All of these drugs, writes Kast, are low-risk drugs when they are used individually, and are all relatively inexpensive and widely available. Phase 3 testing of the regimen will be necessary prior to general use, however.

Reference

Kast RE. Paths for improving bevacizumab available in 2018: the ADZT regimen for better glioblastoma treatment. Med Sci. 2018;6(4); 84. doi:10.3390/medsci6040084.