Activity of CYP3A and Genotypes of CYP3A5 and MDR1 as Predictors of the Clearance and Adverse Effects of Docetaxel, and the Effect of Docetaxel to CYP3A Activity in Previously Untreated Breast Cancer Patients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- docetaxel toxicity
研究概览
简要总结
Twenty patients with verified high risk breast cancer will be included in the study. Patients will receive three cycles of docetaxel followed by three cycles of CEF for their adjuvant treatment. The phenotype of CYP3A and the genotype of CYP3A5 and MDR1 will be assessed. Also the effect of docetaxel in the activity of CYP3A will be measured by peroral midazolam.
Primary Object:
The primary object of this study is to define, if it is possible to predict the clearance and/ or toxicity of docetaxel by assessing
- activity of CYP3A4 by midazolam test (CYP3A4 phenotype)
- CYP3A5 genotype
- MDR1 genotype
Secondary object:
The secondary object of this study is to define whether the treatment with docetaxel alters the activity of CYP3A4 enzyme in previously untreated breast cancer patients.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Subjects may be included in the study only if they meet all of the following criteria:
- •The patient has received information on the purpose of the study and the meaning of the treatment, and has given verbal and written consent to participate in the study. The patient is accessible for treatment and follow-up.
- •Histologically verified diagnosis of breast cancer
- •High risk for recurrence ( node positive or node negative if T2 with histological grade 2 or 3, or Pgr negative)
- •No metastases
- •Females, age =<60
- •No concomitant regular medication which is either substrate, inducer or inhibitor of CYP3A4
排除标准
- •Subjects will be excluded from the study for any of the following reasons:
- •Poor performance status,>=2 according to WHO
- •Inadequate bone marrow reserve defined as:
- •hemoglobin < 100 g/L
- •leukocytes < 3.0 x 10E9/L or neutrophiles < 1.5 x 10E9/L
- •plateless < 120 x 10E9/L
- •Inadequate liver function defined as:
- •ALAT is > 1.5 x units of normal level
- •elevated bilirubin (unless verified Gilbert´s syndrome)
- •alkaline phosphatase is > 2.5 x units of normal level
- •History of concomitant serious physical or psychiatric disease, which makes a regular cytotoxic treatment impossible
- •cardiac insufficience; severe arrhythmia; severe hypertension; cardiac infarction within one year or other active cardiac disease
- •pregnant or lactating patients
- •abuse of alcohol or any narcotic substances
研究组 & 干预措施
Breast cancer
Twenty patients with verified high risk breast cancer will be included in the study.
干预措施: docetaxel + CEF (Drug)
结局指标
主要结局
docetaxel toxicity
There were no specific outcome measures in this study. The chemotherapy was given in a predetermined schedule and additionally blood samples were drawn for genotyping. The adverse events were recorded and compared with the data from genotyping.
次要结局
- survival