If a patient on Bleomycin, Etoposide, and Platinum (BEP) chemotherapy experiences tinnitus, should the treatment be held or discontinued?

Management of Tinnitus During BEP Chemotherapy

Do not discontinue BEP chemotherapy solely for tinnitus; continue treatment with close monitoring and supportive management, as tinnitus is a recognized and expected toxicity that does not require treatment cessation. 1

Understanding Tinnitus as an Expected BEP Toxicity

• Tinnitus is a well-documented and common adverse effect of cisplatin-containing regimens like BEP, affecting most patients during treatment and approximately 40% of long-term survivors. 1, 2

• Tinnitus is explicitly listed as a known toxicity of BEP chemotherapy in ESMO clinical practice guidelines for non-epithelial ovarian cancer and germ cell tumors. 1

• The FDA label for cisplatin confirms that ototoxicity, manifested by tinnitus and/or hearing loss, has been observed in up to 31% of patients treated with a single dose of cisplatin 50 mg/m². 2

Why Treatment Should Continue

• Current guidelines do not recommend holding or discontinuing BEP for tinnitus alone, as this would compromise the curative potential of treatment for highly chemosensitive malignancies like germ cell tumors. 1

• The priority in BEP treatment is achieving cure, particularly in testicular cancer and ovarian germ cell tumors where cure rates remain high even in advanced stages. 1

• Unlike pulmonary toxicity from bleomycin (which may require discontinuation) or severe myelosuppression, tinnitus does not represent an immediately life-threatening or treatment-limiting toxicity. 1

Monitoring and Assessment Strategy

Implement baseline and ongoing audiometric monitoring:

• Perform pure tone audiometry (including frequencies 500-8000 Hz) before chemotherapy initiation and at completion of therapy at minimum. 1

• Encourage patients to report first signs of hearing impairment during treatment, which they often notice when using the telephone or when multiple people are speaking simultaneously. 1

• Document whether tinnitus is bilateral (typical of cisplatin toxicity) versus unilateral, and whether it is associated with hearing loss. 1

Risk factors that warrant heightened vigilance include:

• Increasing cumulative cisplatin dose (dose-dependent toxicity). 1, 2
• Young age at treatment. 1
• Concomitant use of other ototoxic drugs (aminoglycosides, loop diuretics). 1, 3
• Pre-existing hearing impairment. 1
• Renal insufficiency. 1

Supportive Management During Treatment

Provide symptomatic support without interrupting chemotherapy:

• Offer cognitive behavioral therapy (CBT) strategies for tinnitus management, which has evidence for improving quality of life. 1

• Consider sound therapy and other acoustic stimulus reduction techniques to help patients cope with tinnitus symptoms. 1

• Counsel patients that tinnitus may persist long-term, with 40% of survivors reporting tinnitus years after treatment completion. 1

No causative treatment exists for cisplatin-induced ototoxicity:

• Sodium thiosulfate cannot be recommended as standard otoprotective treatment in adults due to uncertainty regarding potential tumor protection and lack of evidence in adult cancer patients. 1

• Other potential otoprotective agents (amifostine, N-acetylcysteine, vitamin E, etc.) have not shown benefit or lack adequate evidence. 1

Critical Distinction: When to Consider Treatment Modification

The only BEP component that may require discontinuation for toxicity is bleomycin:

• Bleomycin should not be given to patients >40 years old or with pre-existing pulmonary disease due to pulmonary toxicity risk. 1

• Pulmonary toxicity (decreased DLCO) is a more serious concern than ototoxicity and may warrant treatment modification. 1

Tinnitus alone does not meet criteria for treatment discontinuation, unlike severe myelosuppression, renal failure, or life-threatening pulmonary toxicity. 1, 2

Long-Term Follow-Up Considerations

• Audiometric monitoring should continue for several years post-therapy, as ototoxicity can present or worsen years after completion of chemotherapy. 2, 4

• Hearing aids may be beneficial for patients who develop significant hearing loss. 1

• Counsel patients to avoid additional ototoxic exposures (noise pollution, ototoxic medications) after treatment. 5

• Studies show 60-74% of testicular cancer survivors report some form of ototoxicity (tinnitus and/or hearing loss), making this an expected rather than exceptional outcome. 6, 7