• Response rate [ Time Frame: 2005-2009 ] [ Designated as safety issue: No ]
• Toxicity [ Time Frame: 2005-2009 ] [ Designated as safety issue: Yes ]
• Relation of patient polymorphisms to toxicity and activity [ Time Frame: 2005-2009 ] [ Designated as safety issue: Yes ]

• Response rate
• Time to progression
• Relation of patient polymorphisms to toxicity and activity

Capecitabine is active in metastatic breast cancer but the conventional schedule (1250 mg/m2/12 hr 2 weeks on, one week off) produces grade 2 or greater hand and foot syndrome in up to 50% of patients leading to those reductions. There are theoretical reasons to administer S-phase specific agents in continuous, protracted rather than intermittent schedules. Our study compares the standard schedule(1250 mg/m2/12 hr 2 weeks on, one week off)with a continuous administration schedule (800 mg/m2/12hr). The latter administer approximately the same cumulative dose of capecitabine as the standard schedule. The study hypothesis is that grade 2 or greater hand and foot syndrome will be reduced from 50% (standard arm) to 20% (experimental arm).We assume similar antitumor activity in both arms.

Capecitabine is active in metastatic breast cancer but the conventional schedule (1250 mg/m2/12 hr 2 weeks on, one week off) produces grade 2 or greater hand and foot syndrome in up to 50% of patients leading to those reductions. Some authors have tested continuous administration schedules of capecitabine, showing better tolerance and apparently similar antitumor activity. Capecitabine is a pro-drug of 5-FU and mimics an i.v. continuous infusion administration of this antimetabolite. On the other hand, there are theoretical reasons to administer S-phase specific agents in continuous, protracted rather than intermittent schedules. Our study compares the standard schedule(1250 mg/m2/12 hr 2 weeks on, one week off)with a continuous administration schule (800 mg/m2/12hr). The latter schedule administer approximately the same cumulative dose of capecitabine as the standard one. The study hypothesis is that grade 2 or greater hand and foot syndrome will be reduced from 50% (standard arm) to 20% (experimental arm). We assume similar antitumor activity in both arms.

• Experimental: capecitabine 800 mg/m2 twice a day orally continuous administration
• Active Comparator: capecitabine 1250 mg/m2 twice a day x 14 days every 3 weeks

Inclusion Criteria:

• Metastatic breast cancer
• Prior anthracyclines and/or taxanes
• ECOG>2
• Measurable disease by RECIST
• Age 18-75

Exclusion Criteria:

• Known hypersensitivity or toxic reactions to fluoropyrimidines
• Prior capecitabine therapy
• Prior cardiac disease
• Relevant renal nal insufficiency (creatinine clearance <30 ml/min)
• Active infection
• Second cancers
• Impaired bone marrow, liver or cardiac function
• More than two lines of chemotherapy for advanced disease.
• Her2 amplification