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

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 (ORadjusted), and respective 95% confidence intervals (95% CI). RESULTS: CYP2C8*3 was significantly associated with increased risks of severe (grades 3-4) neutropenia (ORadjusted 2.11; 95% CI 1.24-3.6; dominant model) and severe thrombocytopenia (ORadjusted 4.93; 95% CI 1.69-14.35; recessive model), whereas ABCB1 variant genotypes (ORadjusted 2.13; 95% CI 1.32-3.42), in association with CYP2C8*3 wild type (GG) (ORadjusted 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.

Perda visual irreversível após uso de paclitaxel / Irreversible visual loss after use of paclitaxel

Descrevemos um caso de perda visual irreversível bilateral em uma paciente de 64 anos após uso prolongado de paclitaxel. Ao exame oftalmológico paciente apresentou acuidade visual (AV) de 20/400 em ambos os olhos (AO) na primeira consulta. À tomografia de coerência óptica (TCO) evidenciou espessamento macular AO. Após seis meses da suspensão do paclitaxel, a paciente apresentava melhora discreta da AV atingindo 20/200 com correção em AO, além da TCO demonstrando resolução do espessamento retiniano.

We describe a case of bilateral irreversible visual loss of a 64 year-old patient after prolonged use of paclitaxel. Patient presented best corrected visual acuity of 20/400 in both eyes at first visit and optical coherence tomography showed increased macular in both eyes.After six months of the interruption of -paclitaxel therapy, the patient showed slight improvement of visual acuity reaching 20/200 in both eyes, while OCT demonstrated resolution of macular edema.