Cancer Chemotherapy Side Effects: Hearing Loss and Tinnitus

As a cancer survivor who is an audiologist, I have experienced the anxiety associated with my diagnosis and the added stress of just how the cancer was going to be managed. Although I have produced several publications and presentations on cancer treatments and hearing loss, it is a completely different experience when you are the patient.

The list of drugs used to effectively treat cancer continues to grow. Despite the obvious benefits, chemotherapy drugs also have side effects. Hearing loss and tinnitus are just two.

As a cancer survivor, I have experienced the anxiety associated with my diagnosis (acute myeloid leukemia) and the added stress of just how the cancer was going to be managed. Although I’ve spent a good deal of my career writing and lecturing about how various drugs and chemicals can be harmful to hearing, I can attest to the fact that the subject of chemotherapy is a completely different experience when you are the patient.

You listen and you ask questions. Lots of questions.

Medication side effects are identified during the different stages of the clinical trials before the Food and Drug Administration (FDA) approves a drug. Some side effects are mild or even rare, but others are obvious (hair loss, weight loss, and yes, hearing loss, tinnitus, and/or balance disorders). The benefits certainly outweigh any risk of an adverse reaction.1

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Some types of chemotherapy, including platinum-based drugs such as cisplatin (Platinol) and carboplatin (Paraplatin), are known to cause damage to your inner ear, causing hearing loss, tinnitus, and/or balance problems.

Common chemotherapy drugs

According to the Cancer Treatment Centers of America,2 the three most common platinum-based drugs are:

Hearing loss or tinnitus caused by these drug can be slow or fast, permanent or temporary, or they may have no effect at all.

If hearing loss occurs, patients will usually report it within the first days of the start of the medication. In some cases, the hearing-related side effects of the drugs resolve after treatment discontinues. However, when it occurs, hearing loss due to platinum derivatives is usually associated with permanent hearing loss.

Clinical trials of ototoxic chemotherapy drugs have identified their otologic effects when used in cancer treatment plans. Therefore, these drugs will have a warning to the prescribers that a hearing evaluation is strongly recommended prior to the commencement of the treatment, with periodic follow-up testing to monitor any loss or a late onset of the loss.

Damaged Hair Cells

Hair cells inside the cochlea—the tiny organ about the size of a pencil eraser responsible for our hearing—can be damaged due to otoxicins and changes in the biochemistry of the inner ear. Likewise, the nerves that transmit sounds from the cochlea to the brain may also become damaged from certain chemotherapy drugs.

Ototoxicity as a drug side effect

The term used to describe the relative risk or propensity of a drug to cause a hearing loss/tinnitus or balance disorder is ototoxicity. The definition literally means “ear (oto) poisoning (toxicity)”; however, the medical and audiology professions use this term to refer to ear-related disorders from any medications and chemicals (not just chemotherapy medications).

The actual cause of any individual’s hearing-related disorder—especially tinnitus—remains fairly elusive in most cases. True, some causes of hearing loss/tinnitus can be readily identified based on the patient’s medical, social, or occupational histories; hearing loss can be directly linked (but not limited) to a person’s work or military noise exposure, concert noise, recreational noise, head trauma, etc.

Although the mechanism causing drug-induced ototoxicity remains unclear with some drugs, it “may involve biochemical and consequent electrophysiological changes in the inner ear and eighth cranial nerve impulse transmission.”3 Platinum-based drugs may damage the myelin sheath which is the plasma membrane that forms around the nerves and protects them. The drug also may affect the fine nerve endings inside the ears.

Most physicians and audiologists working with cancer patients would agree that damage to the hair cells within the cochlea (part of the inner ear) and/or nerves, as well as a build-up of the drug or changes in the biochemistry within the cochlea, are the most-likely causes.

The major classes of chemical compounds known to be ototoxic4 are:

  • Antimicrobials;
  • Antimalarial drugs;
  • Organic and/or industrial solvents, and
  • Some topically administered agents.

Added to the list are also:

  • Salicylates (e.g., aspirin);
  • Non-steroidal anti-inflammatory drugs (NSAIDs, e.g., ibuprofen like Advil or Motrin);
  • Aminoglycoside antibiotics;
  • Loop diuretics, and
  • Chemotherapy agents.

So, it isn’t only chemotherapy drugs that can pose a threat to the ear and hearing during cancer treatment.

Pre-existing otologic issues and risks for changes in hearing

Healthcare providers understand the risk factors for ototoxicity, particularly drug accumulation in the blood and an increased potential for permanent hearing loss. The risk factors include5:

  • Medication dose;
  • Therapy duration;
  • Cumulative lifetime dose;
  • Kidney function;
  • Infusion rate of certain medications (i.e., intravenous furosemide, aminoglycosides);
  • Co-administration of multiple ototoxic medications (e.g., aminoglycosides with loop diuretics);
  • Age;
  • Previous exposure to head and neck radiation (chemotherapeutic agents);
  • Genetic susceptibility, and
  • Family history of ototoxicity.
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In addition to the audiologist establishing a baseline audiogram and monitoring your hearing status, the pharmacist can serve as an invaluable resource for understanding the effects of chemotherapy drugs.

The important role of the pharmacist

If you’ve experienced or are concerned that a cancer drug is ototoxic and threatens to harm your hearing, your pharmacist can provide exact start dates and the dates of increased dosage. Once a timeline has been established from when the drug was dispensed (or increased) and the ear-related side effect was experienced, the audiologist and pharmacist are in a unique position to work together in helping the patient understand and manage their hearing loss. They are then in position to present the information to the prescribing physician for possible medical management.

“What medications do you take and why?”

This question is a typical case history question asked by a physician or audiologist. For the clinician, there is additional work needed to pursue the possibility that the patient’s hearing/balance or tinnitus complaint may be a drug side effect. For example, a number of sources indicate there are well over 220 drugs with tinnitus listed as a reported “side effect” or “adverse drug reaction” (ADR).6-9 This means there is detective work needed to establish whether or not the hearing-related problem is truly pathological or not.

Audiometric Testing and Monitoring

An audiological evaluation is usually scheduled prior to the administration of any known ototoxic chemotherapy drug. Follow-up protocols already exist from the American Academy of Audiology (AAA).10

An audiologist will evaluate hearing and help differentiate between certain types of losses—some of which could be medically or surgically correctable. If there is pre-existing hearing loss, the medication could aggravate the condition. This is why the information from the pharmacist is critical to determine if the tinnitus is either an adverse event or if the hearing loss is getting worse.

Audiologists will have an ototoxic drug monitoring protocol in place based on current research.

Websites for drug side-effects information

No one knows every drug’s indication, dosaging, and side effects. However, the internet can be a tremendous resource. Because anyone can establish a website (beware, there are oodles of sketchy websites on hearing loss and tinnitus!), Winker et al proposed a list of guidelines for websites offering medical information.12 They recommend (in part) that consumers and professionals should look only at websites that have established credibility, an advisory board, and are updated regularly. There should also be appropriate disclaimers that the information in the site is not a substitute for proper medical care.

There are several websites that professionals and consumers can visit to determine if any of their current medications have hearing loss/tinnitus as a reported side effect. These include (but are not limited to):

NOTE: This is not an endorsement by the editor or author.

When you visit a drug information website, simply type in the name of the drug (generic or brand name) and go the “Side Effects” tab. Next, look under “Special Senses” or “Central Nervous System.” If hearing loss, tinnitus, or vertigo is listed, then your next step is to confirm the start date (or date a drug dosage was increased) with your pharmacist. Once the start date has been established and confirmed, then one can suspect that the hearing-related problem is truly an adverse drug reaction.

The prescribing physician should be made aware of this discovery and possible correlation. The medication dosage might be decreased, changed, or discontinued altogether. However, if the prescribed medication is the one that is best for your particular medical condition, then at least the etiology has now been established for possible management by the physician.

Ongoing research

Research and new findings about cancer drugs and the prevention of hearing loss are continually moving forward. As one example, the strong but highly effective cancer chemotherapy drug cisplatin has been followed with treatment in children with the drug sodium thiosulfate with the possible effect of preserving hearing. Alternate dosing strategies that may also help prevent haring damage are also being researched. Additionally, some drug companies are working on developing therapies for the prevention of platinum-induced ototoxicity. More recently, a study has shown that high rates of hearing loss and tinnitus occur not only with platinum drugs, but with another class of chemotherapy drugs called taxanes.

So the subject of cancer treatments and ototoxicity is an area of high interest that scientists continue to research.

Summary

Despite being a side effect or adverse drug reaction, chemotherapy-related hearing issues are manageable and are often temporary (e.g., lasting as long as the drug is taken). The health benefits of the drug usually outweigh the risk of tinnitus; therefore, counseling is a critical component of tinnitus management. With hearing loss that appears to be due to the prescribed drugs for cancer treatment, you should consult with your pharmacist, audiologist, and physician so you can arrive at the best possible decision for your health and hearing.

References

1) Food and Drug Administration (FDA). Basics about clinical trials. Sept 9, 2014. Available at: https://www.fda.gov/patients/clinical-trials-what-patients-need-know/basics-about-clinical-trials

2) Cancer Treatment Centers of America. Hearing loss: The little-known side effect of some chemotherapy drugs. Sept 19, 2017. Available at: https://www.cancercenter.com/community/blog/2017/09/hearing-loss-the-little-known-side-effect-of-some-chemotherapy-drugs

3) Seligmann H, Podoshin L, Ben-David J, Frauds M, Goldsher M. Drug-induced tinnitus and other hearing disorders. Drug Saf. 1996 Mar;14(3):198-212

4) Byung IH, Lee HW, Kim TY, Lim JS, Shin KS. Tinnitus: characteristics, causes, mechanisms, and treatments. J Clin Neurol. 2009 Mar; 5(1): 11–19

5) Coggins MD. Medication-related ototoxicity Today’s Geri Med. 2014[May/Jun];7(3). Available at: <https://www.todaysgeriatricmedicine.com/archive/052714p6.shtml ](https://www.todaysgeriatricmedicine.com/archive/052714p6.shtml)

6) Cone B, Dorn P, Konrad-Martin D, Lister J, Ortiz C, and Schairer K. Ototoxic Medications (Medication Effects). 2018. Available at: https://www.asha.org/public/hearing/ototoxic-medications/

7) DiSogra RM. Adverse drug reactions and audiology practice, 3rd ed [PDF]. Audiology Today, Sept 2008. Available at https://tucsonaudiology.files.wordpress.com/2009/08/adverse-drug-reactions-2008.pdf

8) DiSogra RM. The impact of pharmaceutical side effects on audiological and vestibular measurements. Semin Hear. 2019[May]; 40(2):97-103. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486369/

9) Elgoyen AB, Langguth B, Now M, Schecklmann M, De Ridder, D, Vanneste S. Identifying tinnitus-related genes based on a side-effect network analysis. CPT Pharmacometrics Syst Pharmacol. 2014 Jan 29;3(1):e97. Available at: https://pubmed.ncbi.nlm.nih.gov/24477090/

10) American Academy of Audiology (AAA). AAA Position Statement and Clinical Practice Guidelines: Ototoxicity Monitoring [PDF]. Oct 2009. Available at: https://audiology-web.s3.amazonaws.com/migrated/OtoMonGuidelines.pdf_539974c40999c1.58842217.pdf

11) Lanvers-Kaminsky C, Zehnhoff-Dinnesen AA, Parfitt R, Ciarimboli, G. Drug-induced ototoxicity: mechanisms, pharmacogenetics, and protective strategies. Clin pharmac Ther. 2017Apr;101(4):491-500. Available at: https://pubmed.ncbi.nlm.nih.gov/28002638/

12) Winker MA, Flanagin A, Chi-Lum B, White J, Andrews K, Kennett RL, DeAngelis CD, Musacchio RA. Guidelines for medical and health information sites on the internet - principles governing AMA Web Sites. J Amer Med Assn. 2000;283(12):1600-1606. Available at: https://jamanetwork.com/journals/jama/fullarticle/192531