Therapeutic Dose Monitoring of Epirubicin, Cyclophosphamide, Docetaxel, Paclitaxel, and Doxorubicin in Female Breast Cancer Patients

The primary objective of the study is to measure the exposure (AUC) of cytotoxic drugs, including **epirubicin**, **cyclophosphamide**, **docetaxel**, **paclitaxel**, and **doxorubicin**, which are routinely used in the treatment of breast cancer. The study aims to identify correlations between drug exposure and side effects, with the clinical intention of enabling individualized dose adjustments to prevent both over-treatment and under-treatment in future patients. This is clinically relevant as it seeks to optimize therapeutic efficacy while minimizing adverse effects, thereby improving patient outcomes.

Secondary objectives include:

• Identifying correlations between exposure (AUC) and various toxicities, such as hematologic, liver, cardiac, and ovarian toxicity.
• Exploring the relationship between exposure (AUC) and patients' quality of life.
• Assessing the potential of genetic predispositions for drug metabolism to identify patients at risk of under- or overdose.
• Investigating correlations between exposure (AUC) and tumor response in patients receiving neo-adjuvant treatment.
• Examining the influence of factors like BMI, age, smoking habits, and renal status on exposure (AUC).
• Determining the relationship between drug exposure (AUC) and medical care needs, employment level, and recovery time.
• Comparing total and recurrence-free survival between patients with varying levels of exposure (AUC).
• Evaluating the prevalence of severe adverse events in relation to exposure levels (AUC).
• Comparing dose measurements in capillary versus venous blood samples.
• Identifying correlations between exposure (AUC) and circulating extracellular vesicles.
• Exploring correlations between exposure (AUC) and health state utility values.
• Assessing differences in healthcare costs associated with severe adverse events based on exposure levels (AUC).

The clinical trial involves **female** participants diagnosed with **breast cancer**. The study population includes women aged 18 years and older, who are undergoing treatment with one or more of the following cytotoxic drugs: epirubicin, cyclophosphamide, docetaxel, paclitaxel, and doxorubicin. Participants are required to provide written informed consent. The trial does not include male subjects or vulnerable populations. The sponsor has not provided information regarding the total number of participants. The selection of participants is based on their current treatment regimen, and no specific lifestyle considerations such as diet or physical activity are highlighted. The study aims to explore the correlation between drug exposure and side effects to facilitate individualized dose adjustments in future treatments.

The clinical trial is designed to evaluate the therapeutic dose monitoring of cytotoxic drugs commonly used in the treatment of **breast cancer**. The trial employs a **randomized, double-blind, controlled** methodology to ensure the reliability and validity of the results. The study is expected to span from June 1, 2017, to December 31, 2026, providing a comprehensive analysis over several years. Participants will be involved in a series of study visits, beginning with an inclusion visit where eligibility is confirmed based on criteria such as being female, aged 18 years or older, and receiving treatment with drugs like **docetaxel**, **cyclophosphamide**, **epirubicin hydrochloride**, **paclitaxel**, or **doxorubicin hydrochloride**. Written informed consent is also required.

Following the inclusion visit, participants will undergo regular follow-up visits to monitor drug exposure and side effects, with the primary endpoint being the measurement of grade 1-2 anemia incidence in two exposure groups. Secondary endpoints include correlations between drug exposure and various toxicities, quality of life, genetic predispositions, and tumor response. The end-of-study visit will conclude the participant's involvement, summarizing the findings and any necessary adjustments to treatment protocols. The expected length of participant involvement varies depending on the treatment regimen, with the maximum treatment period ranging from 1 to 19 weeks. Conditions that may lead to early termination from the study include withdrawal of consent or adverse events that compromise participant safety.

The clinical trial involves the administration of several **cytotoxic drugs** for the treatment of breast cancer. The first experimental medication is **Docetaxel Ebewe**, a solution for infusion with a concentration of 10 mg/ml. The active substance is **docetaxel**, a chemical compound. The medication is administered via infusion, with a maximum daily dose of 1 mg/m² and a total dose not exceeding 200 mg over a treatment period of up to 3 weeks.

Another experimental treatment is **Sendoxan**, a solution for injection containing **cyclophosphamide** as the active substance. This chemical compound is administered through infusion. The dosing regimen allows for a maximum daily dose of 1 mg/m², with a total dose limit of 2000 mg over a maximum treatment period of 19 weeks.

**Epirubicin Accord** is also utilized in this trial, available as a solution for injection/infusion with a concentration of 2 mg/ml. The active substance is **epirubicin hydrochloride**, administered via infusion. The dosing schedule permits a maximum daily dose of 1 mg/m², with a cumulative dose not exceeding 550 mg over a 19-week period.

The trial includes **Paclitaxel Accord**, a solution for infusion with a concentration of 6 mg/ml. The active substance, **paclitaxel**, is administered through infusion. The dosing protocol specifies a maximum daily dose of 1 mg/m², with a total dose cap of 80 mg over a treatment period of 1 week.

Lastly, **Doxorubicin Accord** is administered as a solution for infusion with a concentration of 2 mg/ml. The active substance is **doxorubicin hydrochloride**, delivered via infusion. The dosing regimen allows for a maximum daily dose of 1 mg/m², with a total dose limit of 550 mg over a maximum treatment period of 19 weeks.

All medications are administered in accordance with the specified dosing schedules, and participant compliance is monitored throughout the trial to ensure adherence to the treatment protocols. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are mentioned in the trial documentation.

Efficacy in the clinical trial titled "TailorDose®-II: Therapeutic dose monitoring of commonly used cytostatic drugs/regimes indicated for breast cancer" will be assessed through a series of primary and secondary endpoints. The primary endpoint focuses on measuring the incidence of grade 1-2 anemia, as defined by CTC v.4, in two exposure groups (high and low) among patients treated with **epirubicin** and **cyclophosphamide**. This will help determine the correlation between drug exposure and the occurrence of anemia.

Secondary endpoints aim to explore various correlations between drug exposure, measured as area under the curve (AUC), and several factors including hematologic, liver, cardiac, and ovarian toxicity, as well as patients' quality of life. The study will also investigate the potential for genetic predispositions in drug metabolism to identify patients at risk of under- or overdose. Additional analyses will assess the relationship between drug exposure and tumor response in patients receiving neo-adjuvant treatment, as well as the impact of BMI, age, smoking habits, and renal status on exposure levels.

Further secondary endpoints include examining the relationship between drug exposure and medical care needs, employment levels, recovery time, and survival rates. The study will also compare dose measurements in capillary versus venous blood samples and explore correlations between exposure and circulating extracellular vesicles, health state utility values, and healthcare costs associated with severe adverse events. These assessments will be conducted using validated scales and laboratory tests at specified timepoints throughout the trial duration, which is estimated to conclude by December 31, 2026.