Page 28 - August 2022_Fulldraftforflipbook_revised

Shrem et al

1. Chemotherapy and cannabinoids is not recommended outside of clin-
ical trials. There are small clinical trials demonstrating
Chemotherapy is an integral component in the management benefit of exercise, acupuncture, and electrocutaneous
of advanced TC and most often consists of bleomycin, eto- treatments; however, larger, definitive studies are need-
12
poside, and cisplatin (BEP) but may also include ifosfamide, ed to confirm efficacy and clarify risks.
paclitaxel, or carboplatin. For other cancers, strategies to • Depending on the degree of motor impairment, physio-
1
minimize chemotherapy toxicity may include treatment therapy and occupational therapy may be beneficial. 12
delays or dose reductions; however, this is not an option in
5
TC, as these maneuvers may impact cure rates. Significant Ototoxicity
interindividual variability exists and increasingly we are
learning of factors, including genomic markers, that may Ototoxicity from cisplatin can cause both bilateral high-
result in increased susceptibility to chemotherapy toxicities. frequency sensorineural hearing loss and tinnitus. Several
6
Long-term toxicities are described below. potential mechanisms exist, with the primary one being
dose-dependent cochlear damage, especially to the outer
Neurotoxicity hair cells. Release of proapoptotic factors and excess pro-
duction of reactive oxygen species can trigger cell death of
13
Peripheral neuropathy (PN) can occur in patients treated with these hair cells.
cisplatin, carboplatin, or paclitaxel, primarily due to effects In a study of 488 TCS, patients were questioned and
in the dorsal root ganglion, where platinum compounds underwent formal audiometric analysis at a median of
accumulate and lead to cell death. This results in an axonal 4.25 years (range 1–30.3 years) post-chemotherapy. Self-
7
neuropathy of predominantly large myelinated sensory fibers. reported hearing loss was noted in 30% and tinnitus in 40%.
Patients often present with paresthesias and dysesthesias Objectively, hearing loss was found in 80%, with severe to
14
distally that, over time, advance proximally. An early sign profound loss in 18%.
of PN is decreased vibratory sensation in the toes and loss Factors that may influence ototoxicity include cumula-
2
of deep tendon reflexes. Autonomic neuropathies can hap- tive cisplatin dose (>400 mg/m ) and older age at diagno-
15
pen but are rare. PN can start during or after chemother- sis. The concurrent use of other ototoxins, noise exposure,
apy and can worsen for months following chemotherapy. hypertension, smoking, and pre-existing hearing loss are
7
Improvement can occur but may be incomplete. other factors that may influence chemotherapy-induced
In one study of 739 TCS, objective evidence of PN was ototoxicity. 15,16 Examples of ototoxins include: amino-
present in 21.7% who received chemotherapy vs. 9.1% glycoside antibiotics, non-steroidal anti-inflammatory drugs
who did not at a median of 11 years from initial treatment (NSAIDs), and salicylates (ASA). 17
(range 3–19 years); however, subjectively, 12.5% of TCS who
received chemotherapy vs. 5.5% who did not reported PN Management recommendations
8
symptoms. Higher long-term serum platinum levels are • No evidence-based preventative therapies for ototoxicity
associated with more severe self-reported chemotherapy- have been shown to be consistently beneficial in TCS
induced neurotoxicity (PN, ototoxicity, and Raynaud’s phe- who receive chemotherapy.
nomenon) 5–20 years post-platinum-based chemotherapy. • Patients should minimize noise exposure, wear hearing
9
Most reports show that cumulative doses >300 mg/m of protection in noisy environments, avoid other ototoxic
2
cisplatin increase PN risk, while almost all patients have drugs, and minimize other potential factors that may
2 10
evidence of PN after a cumulative dose >500–600 mg/m . influence hearing loss, such as hypertension and smok-
In a study of 680 TCS, risk factors for PN include increased ing exposure.
age, smoking, alcohol use, and hypertension. Pre-existing • Formal audiometric analysis should play a role in TCS
PN or predisposing conditions like diabetes mellitus also who have had cisplatin or high-dose carboplatin given
increase the risk of developing PN. 11 that testing detects more hearing loss than subjective
symptoms. We recommend at least one analysis 4 –5
Management recommendations years post-platinum-based chemotherapy and followup
• No evidence-based preventative therapies for PN have based on that evaluation and symptoms. 14
been shown to be consistently beneficial in TCS treated • Men who have moderate or moderately severe hearing
with chemotherapy. loss (by American Speech-Hearing Association criteria)
12
• Treatment of PN primarily involves symptomatic man- should have regularly scheduled audiological followup.
agement. Based on the American Society of Clinical • Hearing aids are recommended for severe to profound
Oncology (ASCO) guidelines, there are trials supporting hearing loss but are often not used for a number of
the use of duloxetine. The use of gabapentin/pregabalin reasons, including financial. 18

258 CUAJ • August 2022 • Volume 16, Issue 8