Impact of drug formulation and free platinum/cisplatin ratio on hypersensitivity reactions to cisplatin: formulation matters

Pincinato, Eder de Carvalho; Visacri, Marília Berlofa; Souza, Cinthia Madeira de; Tuan, Bruna Taliani; Ferrari, G.; Oliveira, Diogo Noin de; Barbosa, Cristina Rosa; Rodrigues, Raphaela Farias; Granja, Silvia; Ambrosio, Rita; Catharino, Rodrigo Ramos; Rosa, Paulo; Lima, Carmen Sílvia Passos; Mazzola, Priscila Gava; Moriel, Patrícia

doi:10.1111/jcpt.12220

Cited by 2 publications

(1 citation statement)

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“…Additionally, in patients with treatment-naïve metastatic disease or platinum-sensitive relapse, CDDP-based regimens are commonly used in clinical practice, with benefits in progression-free survival (PFS) and overall survival (OS) [ 6 , 7 ]. Nonetheless, CDDP is related to significant adverse events, such as nausea, vomiting, nephrotoxicity, hypersensitivity reactions, and ototoxicity [ 3 , 8 , 9 ]. Among these, hearing impairment is a current concern since there are, to date, no effective otoprotective measures, resulting in potentially permanent and quality-of-life-limiting damage [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Association of Clinical Aspects and Genetic Variants with the Severity of Cisplatin-Induced Ototoxicity in Head and Neck Squamous Cell Carcinoma: A Prospective Cohort Study

Macedo

Costa

Carvalho

et al. 2023

Cancers

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Background: Cisplatin (CDDP) is a major ototoxic chemotherapy agent for head and neck squamous cell carcinoma (HNSCC) treatment. Clinicopathological features and genotypes encode different stages of CDDP metabolism, as their coexistence may influence the prevalence and severity of hearing loss. Methods: HNSCC patients under CDDP chemoradiation were prospectively provided with baseline and post-treatment audiometry. Clinicopathological features and genetic variants encoding glutathione S-transferases (GSTT1, GSTM1, GSTP1), nucleotide excision repair (XPC, XPD, XPF, ERCC1), mismatch repair (MLH1, MSH2, MSH3, EXO1), and apoptosis (P53, CASP8, CASP9, CASP3, FAS, FASL)-related proteins were analyzed regarding ototoxicity. Results: Eighty-nine patients were included, with a cumulative CDDP dose of 260 mg/m2. Moderate/severe ototoxicity occurred in 26 (29%) patients, particularly related to hearing loss at frequencies over 3000 Hertz. Race, body-mass index, and cumulative CDDP were independent risk factors. Patients with specific isolated and combined genotypes of GSTM1, GSTP1 c.313A>G, XPC c.2815A>C, XPD c.934G>A, EXO1 c.1762G>A, MSH3 c.3133A>G, FASL c.-844A>T, and P53 c.215G>C SNVs had up to 32.22 higher odds of presenting moderate/severe ototoxicity. Conclusions: Our data present, for the first time, the association of combined inherited nucleotide variants involved in CDDP efflux, DNA repair, and apoptosis with ototoxicity, which could be potential predictors in future clinical and genomic models.

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