Gemcitabine, Doxorubicin and Paclitaxel (GAT) as Neoadjuvant Treatment of Breast Cancer Patients

Phase II Pharmacogenomic and Clinical Trial for the Administration of Gemcitabine-doxorubicin-paclitaxel (GAT) as Neoadjuvant Treatment of Patients With Stage III Breast Cancer

This is a multicenter, open-label, phase II trial to assess the efficacy of the GAT neoadjuvant regimen in patients with stage III breast cancer.

2 treatment cycles of chemotherapy (one cycle = 2 weeks) must be administered to each patient before breast surgery.

The required number of patients has been calculated following Simon's method. 43 patients will be enrolled in two phases: first, 29 patients must be enrolled, and at least 2 pathological complete responses obtained. Patients recruitment will continue until 43 patients have been enrolled. Assumptions are that there is a 95% probability to obtain a rate of pathological complete responses of at least 10%.

Inclusion Criteria:

• Stage III breast cancer disease, with histological confirmation by true-cut or open-biopsy.
• Ages between 18 and 75 years old. Patients older than 70 must have an adequate quality of life to be eligible.
• Patients cannot have received previous treatment with chemotherapy, hormone therapy, radiotherapy or immune therapy.
• Performance status of 0,1, 2 Eastern Cooperative Oncology Group (ECOG).
• At least a 6 month life expectancy.
• Neutrophils > 1500; platelets > 100000; haemoglobin > 10 mg/dL.
• Adequate renal and hepatic functions, with serum creatinine < 1.2 mg/dl and total bilirubin < 2 mg/dl.
• Adequate contraceptive methods during the study and up to 3 months after.
• Adequate cardiac function assessed by physical exam, electrocardiogram and left ventricular ejection fraction > 55%.

Exclusion Criteria:

• Inflammatory carcinoma or stage I, II or IV breast cancer disease.
• Males.
• Active infection.
• Other neoplasms except for basal skin carcinoma or cervical in situ carcinoma adequately treated. Other previous neoplasms are allowed if diagnosed and treated more than 5 years before study registration.
• Concomitant serious disease provoking organ failure (heart, renal, hepatic, respiratory).
• Pre-existing motor or sensorial neuropathy > grade 1.
• Inability for treatment compliance.
• History of hypersensitivity to compounds such as cremophor, cyclosporine or vitamin K.
• History of arrhythmias or congestive heart failure, even when controlled; or active cardiac blocking of second or third grade.
• History of myocardial infarction in the previous 6 months.
• Hypertension not controlled.
• Pregnant or lactating women.