Conditions: Metastatic Breast Cancer
Keywords: capecitabine schedule breast cancer
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 195
Healthy volunteers: no

Brief summary:
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. The investigators 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). The investigators assume similar antitumor activity in both arms.

Detailed description:
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). The investigators assume similar antitumor activity in both arms.

Arms:
arm 1: Capecitabine will be administered orally at a dose of 1250 mg/m2 twice-daily (in the morning and in the evening, the equivalent of a total daily dose of 2500 mg/m2) for 14 days, in 3 week cycles with a resting period of 7 days,until disease progression or severe toxicity. Dose adjustments were made in patients with grade 3 or greater diarrhea or hand and food syndrome. arm 2: Capecitabine 800 mg/m2 orally twice-daily (in the morning and in the evening the equivalent of one dose of 1600 mg/m2) for 21 days, in 3 week cycles without resting period, until disease progression or severe toxicity. Dose adjustments were made in patients with grade 3 or greater diarrhea or hand and food syndrome.

Interventions: intervention 1: Capecitabine
Intervention descriptions: intervention 1: None

Protocol document: