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Pharmacogenetics of cisplatin in head and neck squamous cell carcinoma

Grant number: 12/01807-2
Support type:Regular Research Grants
Duration: August 01, 2012 - July 31, 2014
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Carmen Silvia Passos Lima
Grantee:Carmen Silvia Passos Lima
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Assoc. researchers:Albina Messias de Almeida Milani Altemani ; Carlos Takahiro Chone ; Celso Darío Ramos ; Patricia Moriel

Abstract

The head and neck squamous cell carcinoma (HNSCC) is a serious health problem worldwide. Cisplatin (CDDP) associated with radiotherapy is used in the treatment for HNSCC patients. It is well known that both the response to treatment and its collateral effects vary from individual to individual. A possible explanation for this can be the genetic variability in the metabolism of CDDP. The aim of this study is to verify if the inherited ability to CDDP detoxification, in the DNA damage repair induced for it and apoptosis of damage cells alter therapeutic and collateral effects of treatment in patients with HNSCC. It will be evaluated, prospectively, 100 patients with HNSCC 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. The human papillomavirus identification will be performed by immunohistochemistry of tumor fragments obtained at the diagnosis. Patients will receive standardized supportive. Treatment collateral effects will be 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 EDTA-51Cr and acoustic acuity tests, respectively, before and after treatment. The polymorphisms genotypes GSTM1, GSTT1, GSTP1 Ile105Val, XPC Lys939Gln, XPD Lys751Gln, XPD Asp312Asn, XPF T30028C, ERCC1 C118T, MSH2 IVS1+9G>C, MSH3 Ala1045Thr, MLH1 G-93A, EXO1 P757L, EXO1 K589E, P53 Arg72Pro, CASP3 A-928G, CASP3 IVS1-15G>T, CASP8 -652 6N ins/del, CASP9 A-1263G, CASP9 C-712T, FAS G-1377A, FAS A-670G, FASL C-844T will be analyzed by polymerase chain reaction (PCR) and enzymatic digestion or Real-Time PCR of DNA samples extracted from peripheral blood. The doses of CDDP in urine will be performed by high performance liquid chromatography (HPLC). The response treatment will be assessed by physical examination, direct nasofibrolaryngoscopy and computed tomography of the neck and chest, according to Response Evaluation Criteria in Solid Tumors (RECIST) and single photon emission computer tomography (SPECT-CT). 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. (AU)

Scientific publications (8)
(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)
CARVALHO, BRUNA FERNANDES; COSTA, ERICKA FRANCISLAINE DIAS; LOPES-AGUIAR, LEISA; LIUTTI, VITOR TEIXEIRA; LEAL, FREDERICO; VASCONCELOS, VIVIAN CASTRO ANTUNES; RINCK-JUNIOR, JOSE AUGUSTO; LOURENCO, GUSTAVO JACOB; LIMA, CARMEN SILVIA PASSOS. Influence ofCASP9c.-1339A>G andCASP3c.-1191A>G variants in outcome of patients with head and neck squamous cell carcinoma. JOURNAL OF ORAL PATHOLOGY & MEDICINE, v. 49, n. 10 SEP 2020. Web of Science Citations: 0.
DIAS COSTA, ERICKA FRANCISLAINE; LOPES-AGUIAR, LEISA; NOGUEIRA, GUILHERME SILVA; PENNA LIMA, TATHIANE REGINE; RINCK-JUNIOR, JOSE AUGUSTO; LOURENCO, GUSTAVO JACOB; PASSOS LIMA, CARMEN SILVIA. CASP9 c.-1339A > G and CASP3 c.-1191A > G polymorphisms alter susceptibility and clinical aspects of head and neck squamous cell carcinoma. HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, v. 41, n. 8, p. 2665-2670, AUG 2019. Web of Science Citations: 0.
CARRON, JULIANA; LOPES-AGUIAR, LEISA; DIAS COSTA, ERICKA FRANCISLAINE; SILVA NOGUEIRA, GUILHERME AUGUSTO; PENNA LIMA, TATHIANE REGINE; PINCINATO, EDER CARVALHO; VISACRI, MARILIA BERLOFA; FRANCA QUINTANILHA, JULIA COELHO; MORIEL, PATRICIA; LOURENCO, GUSTAVO JACOB; PASSOS LIMA, CARMEN SILVIA. GSTP1 c.313A > G, XPD c.934G > A, XPF c.2505T > C and CASP9 c.-1339A > G Polymorphisms and Severity of Vomiting in Head and Neck Cancer Patients treated with Cisplatin Chemoradiation. BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, v. 121, n. 6, p. 520-525, DEC 2017. Web of Science Citations: 3.
VISACRI, MARILIA BERLOFA; PINCINATO, EDER DE CARVALHO; FERRARI, GRAZIELE BALDAN; FRANCA QUINTANILHA, JULIA COELHO; MAZZOLA, PRISCILA GAVA; PASSOS LIMA, CARMEN SILVIA; MORIEL, PATRICIA. Adverse drug reactions and kinetics of cisplatin excretion in urine of patients undergoing cisplatin chemotherapy and radiotherapy for head and neck cancer: a prospective study. DARU-JOURNAL OF PHARMACEUTICAL SCIENCES, v. 25, APR 24 2017. Web of Science Citations: 5.
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.
SILVA NOGUEIRA, GUILHERME AUGUSTO; LOURENCO, GUSTAVO JACOB; MARTINS OLIVEIRA, CAMILA BORGES; LIMA MARSON, FERNANDO AUGUSTO; LOPES-AGUIAR, LEISA; DIAS COSTA, ERICKA FRANCISLAINE; PENNA LIMA, TATHIANE REGINE; LIUTTI, VITOR TEIXEIRA; LEAL, FREDERICO; ANTUNES SANTOS, VIVIAN CASTRO; RINCK-JUNIOR, JOSE AUGUSTO; PASSOS LIMA, CARMEN SILVIA. Association between genetic polymorphisms in DNA mismatch repair-related genes with risk and prognosis of head and neck squamous cell carcinoma. International Journal of Cancer, v. 137, n. 4, p. 810-818, AUG 15 2015. Web of Science Citations: 19.
VISACRI, MARILIA BERLOFA; FERRARI, GRAZIELE BALDAN; DIAS, PAMELA; PIMENTEL, RAFAELA; DE SOUZA, CINTHIA MADEIRA; LOURENCO COSTA, ANNA PAULA; PINCINATO, EDER DE CARVALHO; PASSOS LIMA, CARMEN SILVIA; MAZZOLA, PRISCILA GAVA; MORIEL, PATRICIA. Quality of Life of Patients with Squamous Cell Carcinoma of the Head and Neck Receiving High-Dose Cisplatin Chemotherapy and Radiotherapy. SOUTHERN MEDICAL JOURNAL, v. 108, n. 6, p. 343-349, JUN 2015. Web of Science Citations: 5.
LOPES-AGUIAR, LEISA; VISACRI, MARILIA BERLOFA; LOPES NOURANI, CAROLINA MARQUES; DIAS COSTA, ERICKA FRANCISLAINE; SILVA NOGUEIRA, GUILHERME AUGUSTO; PENNA LIMA, TATHIANE REGINE; PINCINATO, EDER CARVALHO; MORIEL, PATRICIA; CARRASCO ALTEMANI, JOAO MAURICIO; PASSOS LIMA, CARMEN SILVIA. Do Genetic Polymorphisms Modulate Response Rate and Toxicity of Cisplatin Associated With Radiotherapy in Laryngeal Squamous Cell Carcinoma? A Case Report. MEDICINE, v. 94, n. 16 APR 2015. Web of Science Citations: 5.

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