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01-08-2019 | Ovarian Cancer | Gynecologic Oncology

Impact of gene polymorphisms on the systemic toxicity to paclitaxel/carboplatin chemotherapy for treatment of gynecologic cancers

Authors: Clarissa Lourenço de Castro, Luiz Carlos da Costa Junior, Letícia Vieira Lourenço, Karine Souza Seba, Taiana Sousa Lopes da Silva, Rosane Vianna-Jorge

Published in: Archives of Gynecology and Obstetrics | Issue 2/2019

Abstract

Purpose

Gynecologic malignancies are often detected in advanced stages, requiring chemotherapy with taxane/platinum combinations, which may cause severe toxicities, such as neutropenia and peripheral neuropathy. Gene polymorphisms are suspected as possible causes for the interindividual variability on chemotherapy toxicities.

Objective

To evaluate the role of ABCB1 1236C>T, 3435C>T; CYP2C8*3; CYP3A5*3C variants on paclitaxel/carboplatin toxicities.

Methods

A cohort of 503 gynecologic cancer patients treated with paclitaxel/carboplatin at the Brazilian National Cancer Institute (INCA-Brazil) was recruited (2013–2017). Polymorphisms were genotyped by real-time PCR, and toxicities were evaluated by patients’ interviews at each chemotherapy cycle and by data collection from electronic records. The association of clinical features and genotypes with severe toxicities was estimated using Pearson’s Chi square tests and multiple regression analyses, with calculation of adjusted odds ratios (OR_adjusted), and respective 95% confidence intervals (95% CI).

Results

CYP2C8*3 was significantly associated with increased risks of severe (grades 3–4) neutropenia (OR_adjusted 2.11; 95% CI 1.24–3.6; dominant model) and severe thrombocytopenia (OR_adjusted 4.93; 95% CI 1.69–14.35; recessive model), whereas ABCB1 variant genotypes (OR_adjusted 2.13; 95% CI 1.32–3.42), in association with CYP2C8*3 wild type (GG) (OR_adjusted 1.93; 95% CI 1.17–3.19), were predictive of severe fatigue.

Conclusions

The present study suggests that CYP2C8*3 is a potential predictor of hematological toxicities related to paclitaxel/carboplatin treatment. Since hematological toxicities, especially neutropenia, may lead to dose delay or treatment interruption, such prognostic evaluation may contribute to clinical management of selected patients with paclitaxel-based chemotherapy.

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Title: Impact of gene polymorphisms on the systemic toxicity to paclitaxel/carboplatin chemotherapy for treatment of gynecologic cancers
Authors: Clarissa Lourenço de Castro
Luiz Carlos da Costa Junior
Letícia Vieira Lourenço
Karine Souza Seba
Taiana Sousa Lopes da Silva
Rosane Vianna-Jorge
Publication date: 01-08-2019
Publisher: Springer Berlin Heidelberg
Keywords: Ovarian Cancer
Ovarian Cancer
Neutropenia
Gynecologic Cancer
Thrombocytopenia
Cytostatic Therapy
Published in: Archives of Gynecology and Obstetrics / Issue 2/2019
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-019-05197-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Impact of gene polymorphisms on the systemic toxicity to paclitaxel/carboplatin chemotherapy for treatment of gynecologic cancers

Abstract

Purpose

Objective

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Objective

Methods

Results

Conclusions

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