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Efficacy and Toxicity of Vincristine and CYP3A5 Genetic Polymorphism in Rhabdomyosarcoma Pediatric Egyptian Patients.
Shalaby, Norhan; Zaki, Hala F; Badary, Osama A; Kamal, Sherif; Nagy, Mohamed; Makhlouf, Dalia; Elnashar, Amr; Elnadi, Enas; Abdelshafi, Sameh A; Abouelnaga, Sherif; Saber, Mona M.
Afiliación
  • Shalaby N; Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
  • Zaki HF; Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
  • Badary OA; Clinical Pharmacy Department, Faculty of Pharmacy, Misr University for Science and Technology, Egypt.
  • Kamal S; Egypt Healthcare authority, Cairo, Egypt.
  • Nagy M; Pharmaceutical Services Department and Personalized Medication Management Unit, Children's Cancer Hospital Egypt (57357), Cairo, Egypt.
  • Makhlouf D; Research Department, Children's Cancer Hospital Egypt (57357), Cairo, Egypt.
  • Elnashar A; Pediatric Medical Oncology, Beni Suef University and Children's Cancer Hospital Egypt (57357), Cairo, Egypt.
  • Elnadi E; Pediatric Oncology Department. National Cancer Institute; Cairo University and Children's Cancer Hospital Egypt 57357, Cairo, Egypt.
  • Abdelshafi SA; Research Department, Children's Cancer Hospital Egypt (57357), Cairo, Egypt.
  • Abouelnaga S; Pediatric Oncology Department. National Cancer Institute; Cairo University and Children's Cancer Hospital Egypt 57357, Cairo, Egypt.
  • Saber MM; Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Asian Pac J Cancer Prev ; 25(4): 1391-1409, 2024 Apr 01.
Article en En | MEDLINE | ID: mdl-38680001
ABSTRACT

BACKGROUND:

Rhabdomyosarcoma (RMS) is a rare cancer that develops in soft tissue, particularly skeletal muscle tissue and occasionally hollow organs like the bladder or uterus. Vincristine (VCR) is the main therapy used in treatment of RMS, it is an alkaloid produced from vinca and it is one of the most commonly prescribed drugs in pediatric oncology for the treatment of a number of tumors. The CYP3A5 enzyme is responsible for vincristine metabolism. The effect of CYP3A5 genetic polymorphism on the efficacy and toxicity of VCR on RMS patients still needs further research.

METHODS:

Genotyping for CYP3A5 SNPs rs776746, rs10264272 and rs41303343 was performed using Taqman Real-Time PCR assays in a retrospective cohort study of 150 RMS pediatric patients treated with vincristine. The relationship between these genotypes and RMS survival was then examined.

RESULTS:

We found that patients with CYP3A5*3/*3 had the highest incidence of vincristine-induced neuropathy reaching 61.3%. Patients with CYP3A5*1/*3, CYP3A5*3/*6 and the normal metabolizers with CYP3A5*1/*1 had frequencies of 22%, 10.7%, and 4.7%. patients with the lowest frequency of 1.3% were those with the CYP3A5*1/*6 genotype. There was no correlation between the genotypes of CYP3A5*3, CYP3A5*6, CYP3A5*7, and RMS survival. Initial risk, metastasis, response, convulsions, unsteady gait and hepatotoxicity grade had a significant effect on overall survival with p<0.05.

CONCLUSION:

CYP3A5*1/*1 have less severe vincristine-induced neuropathy than CYP3A5 *1/*3, CYP3A5 *1/*6 and CYP3A5 *3/*3, CYP3A5 *3/*6. There is a significant influence of CYP3A5 mutation on neuropathy grade and assist of ADL as a part of neurotoxicity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Rabdomiosarcoma / Vincristina / Polimorfismo de Nucleótido Simple / Citocromo P-450 CYP3A / Antineoplásicos Fitogénicos Límite: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male País/Región como asunto: Africa Idioma: En Revista: Asian Pac J Cancer Prev Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Tailandia
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Rabdomiosarcoma / Vincristina / Polimorfismo de Nucleótido Simple / Citocromo P-450 CYP3A / Antineoplásicos Fitogénicos Límite: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male País/Región como asunto: Africa Idioma: En Revista: Asian Pac J Cancer Prev Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Tailandia