Newly diagnosed pre- or post-operative breast cancer MedDRA version: 21.1 Level: LLT Classification code 10006188 Term: Breast cancer female NOS System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Cyclophosphamide
Pharmaceutical Form: Concentrate and solvent for concentrate for solution for infusion
Product Name: Epirubicin
Pharmaceutical Form: Concentrate and solvent for concent
Sponsors
Karolinska intitutet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female patients aged = 18 years. 2. Treated with any, or a combination, of the drugs cyclophosphamide, epirubicin, doxorubicin, docetaxel and paclitaxel. 3. Written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 175 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 75
Exclusion criteria
Exclusion criteria: 1. Patients fulfilling any of the contraindications mentioned for the studied drugs. 2. Patients treated with a combinatorial regime of docetaxel, carboplatin and trastuzumab. 3. A decision of exclusion is taken by the treating oncologist at the respective oncological clinic.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To measure cytotoxic drugs, i.e., epirubicin, cyclophosphamide, docetaxel, paclitaxel and doxorubicin, used in routine treatment of breast cancer, and to search for correlations between exposure (AUC) and side effects. The intention is to offer future patients individualized dose adjustments to avoid both over- and under-treatment.;Secondary Objective: 1. Correlations between exposure and; hematologic-, liver-, cardiac- and ovarian toxicity 2. Correlations between exposure and the patient’s quality of life 3. Genetic predispositions for drug metabolism to identify patients at increased risk of under- or overdose 4. Correlations between exposure and tumor response in patients receiving neoadjuvant treatment 5. Correlations between BMI, age, smoking habits and renal status vs. exposure 6. Relationship between drug exposure and medical care needs, level of employment 7. Difference in total and recurrence-free survival between patients with low compared to medium/high exposure 8. Difference in the prevalence of SAE in patients with high compared to low exposure 10. Correlations between exposure and circulating extracellular vesicles 11. Correlations between exposure and health state utility values 12. Different healthcare costs associated with severe adverse events in patients exhibiting high compared low exposure?;Primary end point(s): to measure the incidence of grade 1-2 anemia (as defined by CTC v.4) in two exposure groups; high and low, in patients treated with epirubicin and cyclophosphamide.;Timepoint(s) of evaluation of this end point: During chemotherapy treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Correlations between the measured exposures (AUCs) of studied drugs; epirubicin, cyclophosphamide, docetaxel, paclitaxel and doxorubicin, vs.: 1. Measured markers for; hematologic toxicity (RBC, WBC count, neutrophils and platelets), liver toxicity (ALAT, ASAT, ALP and bilirubin), cardiotoxicity (tissue doppler and strain echocardiographic variables, ECG variables, and MRI variables), ovarian cell toxicity (follicle stimulating hormone, luteinizing hormone, estradiol, progesterone, inhibin-B and anti-Müllerian-hormone). 2. Self-reported score on Quality of Life questionnaire (MSAS). 3. Common single nucleotide polymorphisms (SNPs) in genes coding for drug metabolizing enzymes, transporters and targets known to be involved in the metabolism and action of the studied drugs (e.g., CYP1A1, CYP1B1, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP3A4, CYP3A5, GSTM1, GSTM2, GSTP1, ABCB1, CYP2C8). 4. Tumor size (post treatment/baseline). 5. BMI, age, self-reported smoking habits and measured serum creatinine levels. 6. Recorded medical needs, reported level of employment during and after treatment and time for recovery through follow-up. 7. Follow-up of total and recurrence-free survival data in patients participating in this study combined with data from subsequent intervention studies with active dose adjustments. 8. Frequency of observed adverse events of grade 3 or higher. 10. Measurement of the number and composition of extracellular vesicles in blood. 11. Utility values were calculated from self-reported health states (QLU-C10D and EQ-5D-5L). 12. Healthcare costs are associated with adverse events in grades 3 or higher. ;Timepoint(s) of evaluation of this end point: During chemotherapy treatment | — |
Countries
Sweden
Contacts
Public ContactBreast-sarcoma unit
Dept of Oncology, Karolinska university hospital
Outcome results
None listed