CYP2J27 Genotype Predicts Risk of Chemotherapy-Induced Hematologic Toxicity and Reduced Relative Dose Intensity in Ethiopian Breast Cancer Patients.

Authors:
Dr  Daniel Seifu, PhD
Dr Daniel Seifu, PhD
University of Global Health Equity
Associate professor
Medical biochemist
Kigali, Kigali | Rwanda

Front Pharmacol 2019 14;10:481. Epub 2019 May 14.

Division of Clinical Pharmacology, Department of Laboratory of Medicine, Karolinska Institutet Huddinge, Stockholm, Sweden.

Chemotherapy-induced hematologic toxicity is the primary reasons of dose reductions and/or delays, low relative dose intensity (RDI), and predicts anticancer response. We investigated the incidence and predictors of chemotherapy-induced hematologic toxicities and reduced RDI in Ethiopian breast cancer patients, and implication of pharmacogenetics variations. Breast cancer patients ( = 249) were enrolled prospectively to receive cyclophosphamide based chemotherapy. Hematological toxicity (neutropenia, anemia, and thrombocytopenia) were monitored throughout chemotherapy cycle. The primary and secondary outcomes were incidence of grade 3 or 4 toxicity and reduced RDI, respectively. ), , and genotyping were done. Cox proportional hazard and logistic regression were used to estimate risk predictors of toxicity and reduced RDI, respectively. Majority (73.5%) of the patients were < 45 years of age. The incidence of grade 3 or 4 hematological toxicity was 51.0% (95% CI = 44.54-57.46%). Multivariate Cox proportional hazard regression indicated genotype [Hazard ratio (HR) = 1.82; 95% CI = 1.14-2.90], pretreatment grade 1 leukopenia (HR = 2.75; 95% CI = 1.47-5.15) or grade 1 or 2 neutropenia (HR = 2.75; 95% CI = 1.73-4.35) as significant predictors of hematologic toxicities. The odds of having hematologic toxicities was lower in carriers ( = 0.024). The prevalence of reduced RDI was 56.6% (95% CI = 50.3-62.9%). Higher risk of reduced RDI was associated with allele [Adjusted odds ratio (AOR) = 2.79; 95% CI = 1.21-6.46], BMI ≤ 18.4 kg/m (AOR = 5.98; 95% CI = 1.36-26.23), baseline grade 1 leukopenia (AOR = 6.09; 95% CI = 1.24-29.98), and baseline neutropenia (AOR = 3.37; 95% CI = 1.41-8.05). The odds of receiving reduced RDI was lower in patients with genotype (AOR = 0.19; 95% CI = 0.06-0.77). We report high incidence of chemotherapy-induced hematological toxicities causing larger proportion of patients to receive reduced RDI in Ethiopian breast cancer patients. Patients carrying allele and low baseline blood counts are at a higher risk for chemotherapy-induced hematologic toxicities and receiving reduced RDI, and may require prior support and close follow up during chemotherapy.

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Source
https://www.frontiersin.org/article/10.3389/fphar.2019.00481
Publisher Site
http://dx.doi.org/10.3389/fphar.2019.00481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527746PMC
May 2019
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References

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A. A. C. R. Addis Ababa City Cancer Registry. 2014

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