Abstract 5044
Background
Cisplatin is a widely used chemotherapeutic agent for multiple indications. Unfortunately, in a substantial set of patients treated with cisplatin acute kidney injury (AKI) occurs. A recent case report suggested single nucleotide polymorphisms (SNPs) in the COMT gene might be associated with increased cisplatin-induced nephrotoxicity (de Jong et al., BJCP, 2017). Here, we assessed the association of 3 SNPs in this gene with cisplatin-induced nephrotoxicity in our patient population.
Methods
Whole blood samples and serum creatinine concentrations (Scr) of 556 patients who received cisplatin between 2005-2019 were available. The 1947 G>A (Val158Met, rs4680), c.615 + 310 C>T (rs4646316) and c.616 – 367 C>T (rs9332377) SNPs were associated with AKI (CTCAE v4.03) using Fisher’s exact test and difference in Scr up to 2 weeks prior to and up to 6 weeks after cisplatin treatment was described.
Results
Median Scr at baseline was 70 μmol/l (inter quartile range (IQR) 59-81). Up to six weeks after the start of cisplatin treatment the median increased to 81 μmol/l (IQR 69-96). The presence of a variant of c.615 + 310C>T was associated with an increased occurrence of AKI ≥ grade 3 toxicity in patients carrying a homozygous variant (Var) compared to wildtype (WT) patients. AKI grade ≥ 3 occurred in 4 out of 31 (13%) homozygous variant patients against 6 out of 317 (2%) patients carrying wildtype alleles (p = 0.005) after correction for age in a multivariable model. Dehydration occurred in 14 of the 16 patients with AKI grade 3 (3 of 4 WT, 6 of 6 HT and 5 of 6 Var) and likely is a confounding factor. The remaining SNPs were not significantly associated with AKI or difference in Scr.
Conclusions
This study showed that variation in COMT c.615 + 310 C>T (rs4646316) potentially affects the development of AKI grade ≥3, although these results appear to be confounded by dehydration. Therefore, the value of this finding for daily practice is currently unclear and needs to be explored in a prospective setting.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
R.H.J. Mathijssen.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2888 - Development and validation a nomogram based on pathological microscopic features to predict survival in nasopharyngeal carcinoma and guide treatment decision
Presenter: Kuiyuan Liu
Session: Poster Display session 3
Resources:
Abstract
3607 - Deep learning in nasopharyngeal carcinoma: a retrospective cohort study of 3D convolutional neural networks on magnetic resonance imaging
Presenter: Meng Yun Qiang
Session: Poster Display session 3
Resources:
Abstract
5848 - Combined androgen blockade in patients with advanced androgen receptor–positive salivary gland carcinoma: Exploratory biomarker analyses
Presenter: Chihiro Fushimi
Session: Poster Display session 3
Resources:
Abstract
4484 - Classification of esthesioneuroblastoma (ENB) based on chromosome (chr) arm gain and loss (CNA) in the setting of a hypomutated genomic landscape
Presenter: Russell Madison
Session: Poster Display session 3
Resources:
Abstract
5753 - Trastuzumab plus docetaxel in patients with advanced HER2–positive salivary duct carcinoma: Exploratory biomarker analyses
Presenter: Hideaki Takahashi
Session: Poster Display session 3
Resources:
Abstract
3373 - Development and characterization of salivary gland cancer organoid cultures
Presenter: Wim Boxtel
Session: Poster Display session 3
Resources:
Abstract
3118 - A parent-of-origin effect of the RB1 mutations in retinoblastoma with low penetrance and variable expressivity
Presenter: Ekaterina Alekseeva
Session: Poster Display session 3
Resources:
Abstract
4512 - The humanistic burden reported by patients diagnosed with Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN) in Europe
Presenter: Prianka Singh
Session: Poster Display session 3
Resources:
Abstract
3961 - Concurrent Chemotherapy and External Radiation Therapy: An Open Label Non-Inferiority Phase III Randomized Controlled Trial of Weekly versus Three Weekly Cisplatin and Radical Radiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: CONCERT trial
Presenter: ATUL SHARMA
Session: Poster Display session 3
Resources:
Abstract
3973 - A randomized phase II study on the OPTimization of IMmunotherapy in squamous carcinoma of the head and neck (SCCHN) – OPTIM (AIO-KHT-0117)
Presenter: Viktor Grünwald
Session: Poster Display session 3
Resources:
Abstract