5-fluorouracil combined with cofactor (5-10 methylenetetrahydrofolate) in treating advanced breast cancer patients

Conditions: Breast Cancer

Summary: a multi-center, open-label, single-arm phase ii trial assessing the efficacy and safety of weekly bolus infusions of 5-fluorouracil combined with cofactor (5-10 methylenetetrahydrofolate) in advanced breast cancer patients who failed anthracycline and taxane chemotherapy regimens.


Eligibility criteria:
inclusion criteria: * signed informed consent. * women with a histologically/cytologically proven diagnosis of advanced adenocarcinoma of the breast. * measurable disease. at least one unidimensionally measurable non-bony lesion with a diameter \>=10 mm using spiral ct scans (use of spiral ct must be documented in medical records and used consistently throughout the study) or \>= 20 mm using conventional ct or mri scans outside the irradiated area according to recist criteria. * patients having failed both prior anthracycline and taxane derivative chemotherapy regimens. anthrocycline and taxane failure definitions as defined in the protocol. * no more than two prior chemotherapy regimens for advanced disease. * performance status (ecog) \ = 70 * age \>= 18 years. * life expectancy \>= 12 weeks. * adequate organ function as shown by the following: 1. wbcs \>= 3.0 x 109/l, absolute neutrophil count (anc)\>= 1.5 x 109/l, platelets \>= 100 x 109/l, hemoglobin \>= 9 g/dl 2. bilirubin \<= 1.25 x the upper limit of normal (uln),aspartate aminotransferase(ast or alanine aminotransferase(alt),= 3 x uln (or \<= 5 x uln in case of liver metastases) 3. serum calcium within normal limits 4. serum albumin within the normal range for the study site 5. creatinine clearance \>= 60 ml/min (cockroft and gault) 6. left ventricular ejection fraction (lvef) within normal limits as shown by echocardiography or scintigraphy (multiple-gated acquisition scan). * patients of childbearing potential must be using medically acceptable contraception for 4 weeks before start of study treatment and 4 months after study treatment completion. patients of childbearing potential must have a negative pregnancy test result within 7 days prior to study treatment initiation. * patients with parenchymal brain metastases must be either adequately controlled following resection or completed appropriate radiation therapy and be receiving a stable corticosteroid dose prior to study entry. patients with leptomeningeal involvement should not be included in the study. exclusion criteria: * her2/neu positive tumor (2+ or 3+). * pregnancy or lactation * systemic cytotoxic anti-cancer therapy within \ 3 months before study entry. * prior 5-fu- and/or capecitabine-based palliative chemotherapy. * extensive prior radiotherapy affecting more than 30% of bone marrow reserves, or bone marrow / stem cell transplantation. * participation in clinical studies of non-approved experimental agents or procedures within \<=4 weeks of study entry. * history of other malignancy, unless cured and the patient has been disease-free for \>=2 years. patients with a history of cervical carcinoma in situ or cured stage i cervical cancer, or of epidermal or basal cell skin cancer, may be eligible for enrollment after discussion with the sponsor. * previous unexpected reaction to fluoropyrimidines, with or without documented deficiency of dihydropyrimidine dehydrogenase, or known hypersensitivity to 5-fu. * psychologic, familial, sociologic or geographic conditions which do not permit compliance with the study protocol and/or study. * significant cardiac disease, including symptomatic ventricular arrhythmia, congestive heart failure, myocardial infarction within 12 months before study entry. * concomitant treatment with any experimental drug or anti-cancer drug, except hormone therapy or bisphosphonates.