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allied
academies
Journal of Pharmacology and Therapeutic Research
Volume 1 Issue 1
Clinical Pharmacy 2017
Notes:
Page 43
December 07-09, 2017 | Rome, Italy
7
th
World Congress on
Clinical Pharmacy and Pharmacy Practice
Clinical outcome and cisplatin excretion
influenced by GSTM1, GSTT1 and GSTP1
ile105val polymorphisms in head and neck
squamous cell carcinoma patients treated
with cisplatin chemoradiation
¹Eder de Carvalho Pincinato, ²Anna Paula L Costa, ²Leisa Lopes-
Aguiar, ²Ericka F D Costa, ²Tathiane R P Lima, ²Patricia Moriel,
and
²Carmen Silvia P Lima
1
University of Campinas, Brazil
2
Mackenzie Presbyterian University, Brazil
Statement of the Problem:
Cisplatin (CDDP) associated
with radiotherapy (RT) is used in treatment of patients
with head and neck squamous cell carcinoma (HNSCC).
The responses to treatment as well as its side effects vary
among individuals, and this fact may be explained by the
genetic variability in metabolism of CDDP. The aim of this
study was to access if inherited ability to cellular CDDP
detoxification, mediated by GSTs enzymes alters the
therapeutic and side effects of CDDP and RT and urinary
concentration of CDDP in HNSCC patients.
Methodology & Theoretical Orientation:
We evaluated,
prospectively, 90 consecutive HNSCC patients, who
received CDDP plus RT as treatment. Genotypes of
GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms
were analyzed by multiplex polymerase chain reaction
(PCR) and PCR followed by restriction enzyme digestion,
respectively, in peripheral blood DNA. Treatment side
effects as well as renal and hearing toxicities were ranked
through questionnaire and laboratory tests. Urinary doses
of CDDP were performed by high performance liquid
chromatography (HPLC).
Findings:
Patients with GSTT1 null genotype presented
less vomiting (20.0% vs. 64.4%; P=0.002), ototoxicity
(41.7% vs. 79.3%; P=0.03), nephrotoxicity (69.94±21.40
vs. 62.87±20.72 EDTA-51Cr mL/min/1.73m²; P=0.03) and
eliminates more CDDP (429.58±116.24 vs. 253.42±95.20
g CDDP/mg creatinine; P=0.04) than those with the
gene. Patients with GSTP1 Ile105Val homozygous variant
genotype had shorter progression-free survival and those
with GSTP1 Ile105Val homozygous wild genotype had
shorter overall survival.
Conclusion & Significance:
Our data indicate that
SCCHN patients with inherited distinct abilities for CDDP
metabolism, associated with GSTT1 and GSTP1 Ile105Val
polymorphisms, exhibit distinct toxicities to treatment and
urinary CDDP excretion. We believe that this data may
constitute preliminary basis of future personalized.
Biography
Eder de Carvalho Pincinato has completed his Doctor degree from University
of Campinas, Brazil. He is a Pharmacist, Assistant Professor of Hematology
and Coordinator of Pharmacy course at Mackenzie Presbyterian University.
eder.pincinato@mackenzie.brEder de Carvalho Pincinato et al., J Pharmacol Ther Res 2017