Safety profile and activity of lower capecitabine dose in patients with metastatic breast cancer.

Purpose: Capecitabine is an orally administered precursor of 5'-deoxy-5-fluorouridine that was rationally designed to generate 5-fluorouracil (5-FU) preferentially in tumor tissue. The drug enables chronic dosing that mimics continuous infusion of 5-FU. Phase II trials of capecitabine at 1250 mg/m2 twice daily for 14 days followed by 7 days of rest, is active in anthracycline- and taxane-pretreated patients; the main toxicity is palmar-plantar erythrodysesthesia, diarrhea, and nausea. To overcome these side effects, the dose has been reduced to 1000 mg/m2 twice daily with a better therapeutic profile and encouraging efficacy. The aim of our study was to confirm safety and activity of capecitabine at lower doses in patients with metastatic breast cancer (MBC).

Patients And Methods: Thirty-seven patients with advanced breast cancer entered the study. The first 7 patients were treated with capecitabine 1250 mg/m2 twice daily (for 14 days followed by 7 days of rest) and the next 30 patients with capecitabine 1000 mg/m2. The median age was 62 years (range, 38-87 years). Thirteen patients were chemotherapy naive and 24 were pretreated with chemotherapy (9 patients, 1 line; 15 patients, > or = 2 lines). Anthracyclines and/or taxane schedules were administered in 22 patients. Soft tissue metastases were documented in 36 patients; visceral metastases in 24 patients; visceral and soft tissue metastases in 23 patients.

Results: Thirty patients were evaluable for response (5 at "higher" dose and 25 at "lower" dose) and all for toxicity. Overall objective response rate was 57% (5 complete responses and 12 partial responses); 95% CI, 39%-74%; stable disease 20% and progressive disease 23%. Eight of 13 chemotherapy-naive patients (61.5%) and 9 of 24 pretreated patients (37.5%) responded to capecitabine, according to the intent-to-treat principle (6 of 9 responses were obtained at a lower dose). Three responses at the "higher" dose and 14 at the "lower" dose were reported. Median time to progression was 7 months (range, 1-38 months) and median overall survival was 19 months (range, 2-47 months). Toxicity was as follows: grade 2/3 palmar-plantar erythrodysesthesia in 9 patients (24%), grade 2/3 asthenia in 7 patients (19%), grade 2 vomiting in 4 patients (11%), grade 2 renal toxicity in 1 patient, grade 2 skin reaction in 1 patient, and suspected cardiac toxicity in 1 patient.

Conclusion: Our study confirmed that a lower dose of capecitabine has a good toxicity profile and is active in patients with MBC.