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Paper Abstract

Is the administration of Mifepristone drug, a safer treatment for acoustic neuroma?

Acoustic neuroma also known as vestibular schwannoma is a tumor that arises due to the excessive growth of Schwann cells. It mainly affects the cranial nerves and symptoms include hearing loss, tinnitus, balance loss, nystagmus, and vertigo[1]. The historical treatment options for this tumor include waiting and watching for the tumor to grow and then removing it, surgical removal, or radiotherapy. Till now no drug has been proven to be effective against this tumor, however, the use of Mifepristone a newer treatment option for acoustic neuroma is discussed here[2].

Mifepristone - How much do you know about it?

Mifepristone, a structurally synthetic steroid, is a glucocorticoid antagonist hormone. It inhibits the action of progesterone, a hormone that helps during pregnancy. Mifepristone is preferably used with Misoprostol in the early stages of pregnancy to stimulate abortion[3].

Mifepristone and acoustic neuroma – Are they related to each other?

  • The exact action of Mifepristone on acoustic neuroma is still not understood completely.

  • Preclinical computational analysis revealed that Mifepristone acts on nuclear factor- κB cells in acoustic neuroma. They belong to the family of transcription factors that controls a large group of genes that participate in various inflammatory and immune reactions. 

  • It also reduced the activity of HE1-193 cells (cells derived from tumor tissue and immortalized for cell culturing), thereby reducing the metabolic activity of cells.

  • In this manner, Mifepristone can either reduce or prevent the growth of tumor cells in acoustic neuroma.

  • It is proven to be more effective in bilateral acoustic neuroma which is seen in a condition called neurofibromatosis -2, where Mifepristone acts on the defective gene that disrupts the function of the merlin protein which produces Schwann cells [3].

Acoustic Neuroma

Current management strategy using mifepristone in acoustic neuroma

With the advancements in technology and investigative clinical trials happening across the globe, there is a paradigm shift in the treatment of acoustic neuroma. Age-old surgical and radiation treatment options may remove the tumor, but they have the disadvantages of damaging the adjacent nerves and surrounding structures resulting in permanent hearing loss, and also other unavoidable complications such as post-surgical trauma, and radiation exposure side effects. Sometimes even after complete removal, the tumors may recur. So attempting drug therapy immediately after the occurrence of symptoms can be considered in acoustic neuroma[4].

 

Initially, drugs that give symptomatic relief can be advised for patients, and then after confirming the presence of the tumor by a series of investigations such as imaging techniques, tumor-suppressing drugs may be preferred. Apart from Mifepristone, several other chemotherapeutic agents which inhibit the growth of several growth receptors that are involved in the tumor progression can also be prescribed. But despite being effective on tumor growth, they are associated with several side effects [5].

 

Mifepristone on the other hand has lesser side effects and is relatively safer. It either reduces the size of the tumor or prevents its further growth by inhibiting the tumor cells' proliferation. It has been proved that in the initial stages where the patient is asymptomatic if Mifepristone is administered, the tumor does not increase in size and the patient does not develop hearing loss or any other associated symptoms. The efficacy of Mifepristone in the treatment of acoustic neuroma is widely established in cell culture. But further studies and longstanding clinical trials should be conducted to determine its success in treating acoustic neuroma patients and its safety aspect in pregnant patients[5].

Conserve till the last reserve

With the use of Mifepristone, a conservative approach can be tried in the acoustic neuroma, without directly proceeding to surgical excision or radiotherapy. But further studies are required in decision-making regarding the usage of this drug in patients with acoustic neuroma particularly pregnant women[3].

References

  1. Gupta, V.K. et al. 'Vestibular Schwannoma: What We Know and Where We are Heading'. Head Neck Pathol. (2020) 14(4), 1058–1066. DOI: 10.1007/s12105-020-01155-x.

  2. Karpinos, M. et al. 'TREATMENT OF ACOUSTIC NEUROMA: STEREOTACTIC RADIOSURGERY VS. MICROSURGERY'. (2002) 54(5), 12.

  3. Sagers, J.E. et al. 'Computational repositioning and preclinical validation of mifepristone for human vestibular schwannoma'. Sci Rep. (2018) 8(1), 5437. DOI: 10.1038/s41598-018-23609-7.

  4. Myrseth, E. et al. 'Treatment of vestibular schwannomas. Why, when and how?'. Acta Neurochir (Wien). (2007) 149(7), 647–660. DOI: 10.1007/s00701-007-1179-0.

  5. Long, J. et al. 'A Review of Drug Therapy in Vestibular Schwannoma'. Drug Des Devel Ther. (2021) 15, 75–85. DOI: 10.2147/DDDT.S280069.

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