Neoadjuvant Doxorubicin and Cyclophosphamide Followed by Docetaxel and S-1 in Breast Cancer
Neoadjuvant Doxorubicin and Cyclophosphamide Followed by Docetaxel and S-1 in Breast Cancer
RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, docetaxel, and S-1, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PURPOSE: This phase II trial is studying giving doxorubicin hydrochloride together with cyclophosphamide, docetaxel, and S-1 before surgery in treating women with stage II or stage III breast cancer.
OBJECTIVES:
Primary
Secondary
OUTLINE: Patients receive neoadjuvant doxorubicin hydrochloride IV and cyclophosphamide IV on day 1. Treatment repeats every 3 weeks for up to 4 courses. Patients then receive docetaxel IV over 1 hour on day 1 and oral S-1 on days 1-14. Treatment repeats every 3 weeks for 4 courses. Two to four weeks later, patients undergo surgery to remove the tumor (either breast-conserving procedures or mastectomy). Patients may then undergo radiotherapy and receive endocrine therapy.
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed invasive primary breast cancer
ErbB2-negative disease OR patient cannot receive trastuzumab treatment
PATIENT CHARACTERISTICS:
Mobile
ECOG performance status 0-1
Normal cardiac function (LVEF > 50%)
Hemoglobin ≥ 10.0 g/dL
Absolute neutrophil count ≥ 1,500/μL
Platelet count ≥ 10 x 10^4/μL
Creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 50 mL/min
Total bilirubin ≤ 1.5 times ULN
AST/ALT ≤ 2.5 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Able to swallow tablet whole with water
No prior motor or sensory neurotoxicity CTCAE ≥ grade 2
No other serious disease or medical condition
No uncontrolled or serious cardiovascular disease, including any of the following:
No history of symptomatic or therapy-requiring cardiac arrhythmia CTCAE grade 3 (e.g., multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, uncontrolled atrial fibrillation)
No asymptomatic sustained ventricular tachycardia
History of atrial fibrillation or cardiac arrhythmia controlled by medication allowed
No uncontrolled infection, unstable peptic ulcer, uncontrolled diabetes, or any other contraindication to corticosteroid administration
No history of infection or any other serious medical event which may cause any functional injury in the affected patient and consequently, interfere with continuing the study treatment
No history of hypersensitivity to taxanes, fluorouracil, or S-1
No significant gastrointestinal malfunction that will affect S-1 absorption
No history of other cancer within the past 5 years except properly treated carcinoma in situ of the uterine cervix or basal cell or squamous cell carcinoma of the skin
No severe psychological or neurological disorder or dementia that would preclude understanding of the informed consent
No psychological, social, family, or geographical condition, or difficult circumstance that would preclude follow-up or compliance with the protocol
PRIOR CONCURRENT THERAPY:
No prior systemic treatment for this cancer (e.g., radiotherapy, chemotherapy, hormone therapy, or biological therapy)
No prior preoperative topical treatments (e.g., incomplete surgery or radiotherapy) for this cancer
No concurrent drug(s) that may potentially cause changes in the pharmacological activity of S-1 formulation, including any of the following: