Capecitabine and Radiation Therapy in Treating Patients With Nonmetastatic Breast Cancer After Surgery

OBJECTIVES:

Primary

• To determine the safety and feasibility of concurrent capecitabine and standard external-beam irradiation in patients with high-risk early stage breast cancer.

Secondary

• To determine the effects of concurrent treatment on cosmesis and wound healing at 1 year.
• To determine the short-term (1-year) risk of recurrence of breast cancer in these patients.

OUTLINE: This is a multicenter study.

Patients undergo external-beam radiotherapy once daily, 5 days a week and concurrently receive oral capecitabine twice daily, 5 days a week Monday through Friday, for approximately 6-7 weeks.

After completion of study therapy, patients are followed at approximately 1 week, 1 month, 6 months, and 12 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed invasive adenocarcinoma of the breast, meeting 1 of the following high-risk criteria:

• T3 or T4 primary tumor
• 4 or more involved axillary lymph nodes (N2 nodal stage)
• Completed surgical excision

• No immediate reconstruction with autologous flap reconstruction

• Patients having tissue expanders or implants placed prior to radiation may be enrolled at the physician's discretion
• No residual breast cancer

• Microscopically positive margins are allowed if a re-excision is not felt to be clinically justified
• Candidate for radiotherapy

• Must not require bilateral radiotherapy
• No metastatic (stage IV) breast cancer by AJCC staging criteria
• Hormone receptor status not specified
• No CNS disorders

PATIENT CHARACTERISTICS:

• Life expectancy ≥ 6 months
• Karnofsky performance status 70-100%
• Menopausal status not specified
• Ambulatory
• Hemoglobin > 9 g/dL
• Platelet count > 100,000/mm³
• ANC > 1,500/mm³
• Serum AST, ALT, and alkaline phosphatase ≤ 2 times upper limit of normal (ULN)
• Total bilirubin normal
• Creatinine clearance > 50 mL/min
• Negative pregnancy test
• Not pregnant or nursing
• Fertile patients must use effective contraception during study and for 30 days after the last study drug administration
• No serious, uncontrolled, concurrent infection(s)
• No diabetes with current or history of delayed wound healing or skin ulcers
• No autoimmune connective tissue disorder
• No prior unanticipated severe reaction to fluoropyrimidine therapy, known sensitivity to 5-fluorouracil, or known dihydropyrimidine dehydrogenase (DPD) deficiency
• No other carcinomas within the last five years except cured non-melanoma skin cancer and in-situ cervical cancer
• No clinically significant cardiac disease (e.g., congestive heart failure, symptomatic coronary artery disease, or cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months
• No other serious uncontrolled medical conditions that the investigator feels might compromise study participation, including any of the following:

• Uncontrolled seizures
• Psychiatric disability judged by the investigator to be clinically significant
• Physically intact upper gastrointestinal tract
• No malabsorption syndrome
• No uncompensated coagulopathy
• No patients whose breast size or body contour puts them at increased risk for skin desquamation from standard radiotherapy
• Able to read and speak English

PRIOR CONCURRENT THERAPY:

• Fully recovered from surgery and chemotherapy with completely healed surgical wounds
• At least 4 weeks since completion of prior chemotherapy regimen, excluding trastuzumab (Herceptin®)

• Concurrent trastuzumab allowed at the physician's discretion
• More than 4 weeks since prior participation in any investigational drug study
• At least 4 weeks since prior and no concurrent sorivudine or brivudine
• More than 2 weeks since prior major surgery
• No prior capecitabine
• No prior radiotherapy to the chest or ipsilateral lymphatics
• No concurrent hormonal therapy during course of chemotherapy or radiation therapy
• No concurrent allopurinol or cimetidine
• Concurrent coumadin is allowed