Multicenter Randomized Phase III Clinical Trial to Compare 6 FAC Cycles(Fluorouracil, Doxorubicin, Cyclophosphamide) vs. 4 FAC Cycles Followed by 8 Weekly Paclitaxel Administrations, as Adjuvant Treatment for Node Negative Operable Breast Cancer Patients
- Written informed consent.
- Histological diagnoses of operable invasive adenocarcinoma of the breast (T1-T3).
Tumors must be HER2 negative. Patients must be free of disease in the axilla (node
negative). If lymphadenectomy is done, at least 10 nodes must be examined. If
sentinel node technique is used, sentinel node must be free of disease. Patients must
present at least one high risk criterion (St. Gallen, 1998) as follows:
- Tumor size > 2 cm; and/or
- ER and PgR negative; and/or
- Histological grade 2-3; and/or
- Age < 35 years old.
- Time window between surgery and study randomization must be less than 60 days.
- Surgery must consist of mastectomy or conservative surgery. Margins free of disease
and ductal carcinoma in situ (DCIS) are required. Lobular carcinoma is not considered
a positive margin.
- Patients must not present evidence of metastatic disease.
- Status of hormone receptors in primary tumor. Results must be available before the
end of adjuvant chemotherapy.
- Status of HER2 in primary tumor, known before randomization. Patients with immune
histochemistry (IHC) 0 or +1 are eligible. For patients with ICH 2+, fluorescent in
situ hybridization (FISH) is mandatory and result must be negative.
- Age >= 18 and <= 70 years old.
- Performance status (Karnofsky index) >= 80.
- Normal electrocardiogram (EKG) in the 12 weeks prior to randomization. If needed,
normal cardiac function must be confirmed by left ventricular ejection fraction
- Laboratory results (within 14 days prior to randomization):
- Hematology: neutrophils >= 1.5 x 10^9/l; platelets >= 100x 10^9/l; hemoglobin
>= 10 mg/dl;
- Hepatic function: total bilirubin <= 1 upper normal limit (UNL); SGOT and SGPT
<= 2.5 UNL; alkaline phosphatase <= 2.5 UNL. If values of SGOT and SGPT > 1.5
UNL are associated with alkaline phosphatase > 2.5 UNL, patient is not eligible.
- Renal function: creatinine <= 175 mmol/l (2 mg/dl); creatinine clearance >= 60
- Complete stage workup during the 12 weeks prior to randomization (mammograms are
allowed within a 20 week time window). All patients must have a bilateral mammogram,
thorax x-ray, abdominal echography and/or computed tomography (CT)-scan. If bone
pain, and/or alkaline phosphatase elevation, a bone scintigraphy is mandatory. This
test is recommended for all patients. Other tests, as clinically indicated.
- Patients able to comply with treatment and study follow-up.
- Negative pregnancy test done in the 14 previous days to randomization.
- Prior systemic therapy for breast cancer.
- Prior therapy with anthracyclines or taxanes (paclitaxel or docetaxel) for any
- Prior radiotherapy for breast cancer.
- Bilateral invasive breast cancer.
- Pregnant or lactating women. Adequate contraceptive methods must be used during
chemotherapy and hormone therapy treatments. Negative pregnancy test in the 14
previous days to randomization.
- Any T4 or N1-3 or M1 tumor.
- HER2 positive breast cancer (IHC 3+ or positive FISH result).
- Pre-existing grade >=2 motor or sensorial neurotoxicity (National Cancer Institute
Common Toxicity Criteria [NCI CTC] v-2.0).
- Any other serious medical pathology, such as congestive heart failure, unstable
angina, history of myocardial infarction during the previous year, uncontrolled HA or
high risk arrhythmias.
- History of neurological or psychiatric disorders, which could preclude the patients
to free informed consent.
- Active uncontrolled infection.
- Active peptic ulcer; unstable diabetes mellitus.
- Previous or current history of neoplasms different from breast cancer, except for
skin carcinoma, cervical in situ carcinoma, or any other tumor curatively treated and
without recurrence in the last 10 years; ductal in situ carcinoma in the same breast;
lobular in situ carcinoma.
- Concomitant treatment with other investigational products. Participation in other
clinical trials with a non-marketed drug in the 20 previous days before
- Concomitant treatment with other therapy for cancer.