Dose-adjusted Adjuvant FEC Compared to Standard FEC for Breast Cancer

Study Overview
=================
Brief Summary
-----------------
This is an open randomized phase III study. The primary objective of this study is to compare FEC adjuvant chemotherapy in operable breast cancer given either as fixed doses calculated according to the patients surface area or with doses adjusted according to leukopenia after course one in order to achieve hematological equitoxicity. The main aim of the study is to test whether chemotherapy dosage aimed at hematological equitoxicity will improve the effect of adjuvant chemotherapy.

Detailed Description
-----------------
Group A, FECStandard(standard FEC) is given 7 courses of 5-fluorouracil-epirubicin (Farmorubicin)-cyclophosphamide with doses based on the patient's surface area. Leukocyte nadir values at day 10, 12 or 13 and 15 are measured. Dose-reductions of one step according to table 8.2.1 are performed in case of leukopenic fever or grade 4 leukopenia. Group B FECTailored(Tailored FEC) receives course one at identical doses to group A. Leukocyte nadir values at day 10,12 or 13 and 15 are measured. Doses of subsequent courses are adjusted to achieve grade 3 leukopenia (leukocyte nadir 1.0 to 2.0) in patients experiencing only grade 0 to 2 leukopenia after course one. Dose-reductions of one step according to table 8.2.1 are performed in case of leukopenic fever or grade 4 leukopenia . Patients achieving only grade 0-2 leukopenia at the first course will be randomized into continued treatment at standard doses (Group A) or to doses tailored to achieve grade 3 leukopenia (Group B). The primary comparisons will be made between these two groups of patients. Patients with grade 3-4 leukopenia after the first course not be randomized but followed according to the protocol and received treatment as group A, FECStandard.

Official Title
-----------------
SBG 2000-1. Individually Dose-adjusted FEC Compared to Standard FEC as Adjuvant Chemotherapy for Node Positive or High-risk Node Negative Breast Cancer. A Randomized Study by the Scandinavian Breast Group

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: 5-FU, epirubicin and cyclophosphamide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Node positive or 2) High-risk node negative# no major cardiovascular morbidity female age 18-60 ECOG/WHO performance status <1 histologically proven invasive breast cancer written or oral witnessed informed consent according to the local Ethics Committee requirements start of adjuvant chemotherapy within 8 weeks after surgery Exclusion Criteria: distant metastases (M1) locally advanced cancer nonradically operated (positive resection margins) pregnancy or lactation leukocyte count < 3.5 x109 /l platelets < 100 x109 /l other serious medical condition previous or concurrent malignancies at other sites, except basal cell carcinoma and carcinoma cervicis uteri in situ

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard<br>Standard FEC (F600, E60, C600) every 3rd week. | Drug: 5-FU, epirubicin and cyclophosphamide<br>* Tailored dose escalation of epirubicin and cyclophosphamide.<br>|
| Experimental: Tailored<br>Tailored FEC (F600, E75-90, C900-1200) every 3rd week. | Drug: 5-FU, epirubicin and cyclophosphamide<br>* Tailored dose escalation of epirubicin and cyclophosphamide.<br>|
| Active Comparator: Registered<br>Non-randomized arm with patients with grade 3-4 leukopenia after first cycle and treated with standard FEC (F600, E60, C600) every 3rd week. | Drug: 5-FU, epirubicin and cyclophosphamide<br>* Tailored dose escalation of epirubicin and cyclophosphamide.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distant disease-free survival. | Distant disease-free survival comparing standard and tailored arm. | 5-10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regio-locally relapsed disease | Regiolocal disease-free survival | 5-10 years | 
| Overall survival | Overall survival | 5-10 years | 
| Toxicity of treatment. | Adverse events | 5-10 years | 
| Leukopenia and correlation to prognosis in distant disease-free survival. | Distant disease-free survival in patients groups based on nadir leukopenia after third cycle. | 5-10 years. | 
| Effect of dose escalation of leukopenia and correlation to prognosis in distant disease-free survival. | Comparing distant disease-free survival difference between patients randomized to tailored and dose-escalated FEC with the Group of patients with standard FEC but with similar grade of leukopenia. | 5-10 years. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Breast Cancer