Phase II Trial of Capecitabine With Fulvestrant for Postmenopausal Women With Hormone Receptor Positive Metastatic Breast Cancer

Exclusion Criteria

• •Prior administration of capecitabine.
• •Prior administration of fulvestrant.
• •Prior chemotherapy for metastatic breast cancer.
• •Radiotherapy ≤ 2 weeks prior to registration, except if to a non-target lesion only or single-dose radiation for palliation. NOTE: Prior radiation to a target lesion(s) is permitted only if there has been clear progression of the lesion since radiation was completed.
• •Life expectancy \<3 months.
• •Serious, uncontrolled, concurrent infection(s).
• •Prior unanticipated severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-fluorouracil or known dihydropyrimidine dehydrogenase (DPD) deficiency.
• •Treatment for other carcinomas within the last 5 years, except cured non-melanoma skin and treated in-situ cervical cancer or superficial bladder tumors (stage Ta or Tis).
• •Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
• •Clinically significant cardiac disease (e.g., congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication)or myocardial infarction within the last 12 months prior to study entry.
• •Active brain metastases. Patients with neurological symptoms must undergo a CT scan or magnetic resonance imaging (MRI) of the brain to exclude active brain metastasis. NOTE: Patients with treated brain metastases are eligible provided they have no evidence of disease and are off definitive therapy (including steroids) ≥ 3 months prior to study entry.
• •Central nervous system (CNS) disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake.
• •Known human immunodeficiency virus or chronic hepatitis B or C.
• •Other serious uncontrolled medical conditions that the investigator feels might compromise study participation.
• •Major surgery within 4 weeks of the start of study treatment, without complete recovery.
• •Lack of physical integrity of the upper GI tract or malabsorption syndrome.
• •Known, existing uncontrolled coagulopathy.
• •Any of the following laboratory values:
• •Abnormal hematologic values (neutrophils \[ANC\]: \<1.5 × 109/L, platelet count: \<100 × 109/L)
• •Impaired renal function (estimated creatinine clearance: \<30 mL/min as calculated with Cockcroft-Gault equation). Note: In patients with moderate renal impairment (calculated creatinine clearance: 30 to 50 mL/min) at baseline, a dose reduction to (-1) of the capecitabine starting dose is required.
• •Serum bilirubin \>1.5 × upper normal limit (ULN).
• •Alanine transaminase (ALT) or aspartate transaminase (AST) \>2.5 × ULN (or \>5 × ULN in the case of liver metastases).
• •Alkaline phosphatase \> 2.5 × ULN (or \>5 × ULN in the case of liver metastases or \>10 × ULN in the case of bone disease).
• •International normalization ratio (INR) \>1.6.
• •History of:
• •* Bleeding diathesis,(ie, disseminated intravascular coagulation \[DIC\], clotting factor deficiency) or
• •* Long-term anticoagulant therapy,(other than antiplatelet therapy and warfarin 1 mg qd for port prophylaxis).
• •History of hypersensitivity to active or inactive excipients of fulvestrant (ie, castor oil or Mannitol).
• •Unwillingness to give written informed consent.
• •Unwillingness to participate or inability to comply with the protocol for the duration of the study.