Do Genetic Polymorphisms Modulate Response Rate and Toxicity of Cisplatin Associated With Radiotherapy in Laryngeal Squamous Cell Carcinoma?. Issue 16 (April 2015)

• Record Type: Journal Article
• Authors: Lopes-Aguiar, Leisa; Visacri, Marília Berlofa; Nourani, Carolina Marques Lopes; Costa, Ericka Francislaine Dias; Nogueira, Guilherme Augusto Silva; Lima, Tathiane Regine Penna; Pincinato, Eder Carvalho; Moriel, Patrícia; Altemani, João Maurício Carrasco; Lima, Carmen Silvia Passos; Kichenadasse., Ganessan
• Is Part Of: Medicine. Volume 94:Issue 16(2015)
• Publication Date: 2015-04
• Subjects: Medicine -- Periodicals; Medicine -- Periodicals; Médecine -- Périodiques; Geneeskunde; Medicine; Periodicals; Periodicals; 610.5
• DOI: 10.1097/MD.0000000000000578
• Languages: English
• ISSNs: 0025-7974

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Abstract</title> <p>Cisplatin (CDDP) plus radiotherapy (RT) has been used to treat advanced laryngeal squamous cell carcinoma (LSCC) patients. Single nucleotide polymorphisms (SNPs) may be responsible for differences in chemo/radiosensitivity and side effects in those patients. We reported an advanced LSCC patient, who obtained durable complete response and unexpected pronounced toxicity during CDDP and RT, possibly due to SNPs in genes that modulate the effects of this therapeutic modality. Case presentation: A 30-year-old man with advanced LSCC obtained durable complete response and severe alopecia and pancytopenia after standard and reduced doses of CDDP and RT. Analyses of SNPs revealed that the patient presented <italic>GSTT1</italic> deletion, variant <italic>MSH3</italic> 1045ThrThr, wild <italic>GSTP1</italic> 105IleIle, and wild <italic>BAX</italic> -248GG genotypes, which were previously described in association with abnormal detoxification, DNA repair, and damaged cell apoptosis, respectively. Seven other advanced LSCC patients with <italic>GSTT1</italic> gene, <italic>MSH3</italic> AlaAla or AlaThr, <italic>GSTP1</italic> IleVal or ValVal, and <italic>BAX</italic> GA or AA genotypes served as controls of the study. Only 1 control presented complete response; the other 6 controls obtained partial response of short duration. Four and 3 controls presented grade 1 or 2 and grade 3 anemia or leukopenia during treatment, respectively. The CDDP level in urine collected after CDDP infusion in the reported patient was lower than the median value obtained in controls, suggesting a higher amount of intracellular CDDP in the reported case.</p> <p>The data suggest, for the first time, that inherited abnormalities in intracellular detoxification of CDDP, DNA repair of lesions induced by CDDP and RT, and damaged cell apoptosis may alter treatment response and toxicity in LSCC, but should be confirmed by large pharmacogenomic studies.</p> </sec> </abstract>