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Polymorphisms in DNA Repair Genes in the Pharmacogenetics of Cisplatin Associated with Radiotherapy in Patients with Head and Neck Squamous Cell Carcinoma

Grant number: 11/15089-1
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2012
Effective date (End): February 28, 2014
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Carmen Silvia Passos Lima
Grantee:Leisa Lopes Aguiar
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The head and neck squamous cell carcinoma (HNSCC) is a serious health problem worldwide. Cisplatin (CDDP) associated with radiotherapy is administrated as neoadjuvant, adjuvant, definitive or palliative treatment for patients with this disease. It is well known that both the response to treatment and its collateral effects vary from individual to individual, what it appears to be explained, at least in part, by genetic variability in the metabolism of CDDP. The aim of this study is to verify if the inherited ability to repair the DNA damage, mediated by ERCC1, XPC, XPD and XPF enzymes alter therapeutic and collateral effects of treatment in patients with HNSCC. It will be evaluated, prospectively, 100 patients with HNSCC of Clinic Oncology ambulatories at the Clinical Hospital, State University of Campinas, will receive CDDP (80-100 mg/m2/dose, D1, D22 and D43) and radiotherapy (7,000 cGy, 35 sessions), as neoadjuvant, definitive or palliative treatment of the disease. Patients will receive standardized supportive care with hydration, antiemetics, analgesics, laxatives and antidiarrheals. Treatment collateral effects will be evaluated and scored (grade 1 to 4) by a specific questionnaire and physical examination, according to the criteria of the National Cancer Institute (NCI). The renal and auditory toxicities will be evaluated through serum creatinine, glomerular filtration rate with ethylenediaminetetraacetic acid labeled with chromium-51 (EDTA-51Cr) and acoustic acuity tests, respectively, before and after treatment. The genotypes of the genes ERCC1, XPC, XPD and XPF will be analyzed by polymerase chain reaction (PCR) and enzymatic digestion of DNA samples from peripheral blood. The doses of CDDP in urine will be performed by high performance liquid chromatography (HPLC) after administration of each dose of chemotherapy. The response rate will be assessed by physical examination, direct nasofibrolaryngoscopy (when appropriated), computed tomography of the neck and chest (when appropriated), according to Response Evaluation Criteria in Solid Tumors (RECIST). The differences between groups will be calculated by Fisher's exact test or chi-square. We believe that the results may contribute to stratify groups of individuals who deserve to receive different doses of CDDP in the treatment of HNSCC.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
LOPES-AGUIAR, LEISA; DIAS COSTA, ERICKA FRANCISLAINE; SILVA NOGUEIRA, GUILHERME AUGUSTO; PENNA LIMA, TATHIANE REGINE; VISACRI, MARILIA BERLOFA; PINCINATO, EDER CARVALHO; CALONGA, LUCIANE; MARIANO, FERNANDA VIVIANE; DE ALMEIDA MILANI ALTEMANI, ALBINA MESSIAS; CARRASCO ALTEMANI, JOAO MAURCIO; COUTINHO-CAMILLO, CLAUDIA MALHEIROS; FERNANDES RIBEIRO ALVES, MARIA ALMERINDA VIEIRA; MORIEL, PATRICIA; RAMOS, CELSO DARIO; CHONE, CARLOS TAKAHIRO; PASSOS LIMA, CARMEN SILVIA. XPD c.934G > A polymorphism of nucleotide excision repair pathway in outcome of head and neck squamous cell carcinoma patients treated with cisplatin chemoradiation. ONCOTARGET, v. 8, n. 10, p. 16190-16201, 2017. Web of Science Citations: 7.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
AGUIAR, Leisa Lopes. Polymorphisms in nucleotide excision DNA repair genes in cisplatin pharmacogenetics associated with radiotherapy in patients with head and neck squamous cell carcinoma. 2014. Master's Dissertation - Universidade Estadual de Campinas. Faculdade de Ciências Médicas.

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