A 19-year-old man being treated with chemotherapy for testicular cancer presents to hospital with tinnitis and high-frequency hearing loss. His creatinine is 1.8 mg/dL. Diuresis with 0.9% NaCl is initiated. Administration of which of the following agents may have prevented these findings?
This man is being treated with cisplatin, a platinum-based compound that is one of the first-line chemotherapeutic agents used for testicular cancer.1
It is well-known to damage the cochlear stereocilia, thereby causing ototoxicity.2 It is also associated with nephrotoxicity.3
In an aqueous environment, the chloride ligands of cisplatin are replaced by water molecules. This generates a positively charged electrophilic moiety that damages DNA.4, 5, 6
Hydration is essential for all patients to prevent cisplatin‐induced nephrotoxicity: 7
- “Specifically, short‐duration, low‐volume, outpatient hydration with magnesium supplementation and mannitol forced diuresis (in select patients) represent best practice principles for the safe use of cisplatin.”8
Amifostine is a cytoprotective adjuvant that decreases incidence of cisplatin-induced toxicity if administered prior to and during cisplatin infusion.9, 10
Mesna decreases the risk of hemorrhagic cystitis in patients being treated with cyclophosphamide.11
N-acetylcysteine decreases the incidence of severe hepatotoxicity caused by acetaminophen overdose. It regenerates reduced glutathione.12
Leucovorin “rescue” (folinic acid) may be used to mitigate myelosuppression, gastrointestinal toxicity, neurotoxicity, and acute kidney injury in patients receiving methotrexate.13, 14, 15
Dexrazoxane is a free-radical chelator that decreases the risk of dilated cardiomyopathy in patients receiving doxorubicin.16
Bottom line:
1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835297/
2) https://www.ncbi.nlm.nih.gov/pubmed/15721567/
3) https://journals.sagepub.com/doi/abs/10.1177/019262338601400215
4) https://www.pnas.org/content/113/41/11507
5) https://www.ncbi.nlm.nih.gov/pubmed/4831344/
6) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153174/
7) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423518/
8) The Oncologist 2017;22:609–619
9) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022215/
10) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2504739/
11) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219308/
12) http://www.saudijgastro.com/article.asp?issn
13) https://www.ncbi.nlm.nih.gov/pubmed/8507221
14) http://theoncologist.alphamedpress.org/content/early/2016/08/05/theoncologist.2015-0164.full.pdf
15) https://theoncologist.alphamedpress.org/content/11/6/694.full
