Phase 2 trial of a novel capecitabine dosing schedule in combination with bevacizumab for patients with metastatic breast cancer

• Published in: Cancer 2011-09, Vol.117 (18), p.4125-4131
• Main Authors: Gajria, Devika, Feigin, Kim, Tan, Lee K., Patil, Sujata, Geneus, Stephanie, Theodoulou, Maria, Norton, Larry, Hudis, Clifford A., Traina, Tiffany A.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Capecitabine; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Female; Fluorouracil - administration & dosage; Fluorouracil - analogs & derivatives; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; metastatic breast cancer; Middle Aged; Neoplasm Metastasis; Tumors
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.25992

BACKGROUND: Capecitabine has antitumor activity in metastatic breast cancer (MBC); however, its optimal dose and schedule remain unclear. Mathematical modeling predicts that a capecitabine schedule 7 days of treatment followed by 7 days of rest (7—7) will improve efficacy and minimize toxicity. Bevacizumab has demonstrated the ability to improve outcomes when it is added to chemotherapy, including capecitabine, in the first‐line and second‐line settings. METHODS: Patients with measurable MBC received oral capecitabine (2000 mg twice daily; 7—7), and intravenous bevacizumab (10 mg/kg every 2 weeks). The primary endpoint was the response rate. Secondary endpoints included toxicity, the clinical benefit rate, and progression‐free survival (PFS). RESULTS: Forty‐one patients were treated. After a median of 7 cycles (range, 1‐32 cycles), partial responses were observed in 20% of patients, and stable disease for ≥6 months was noted in 35% patients. The median PFS was 8 months. The most common treatment‐related toxicities were hand‐foot syndrome (49% grade 2, 20% grade 3/4) hypertension (12% grade 2, 10% grade 3/4), and fatigue (12% grade 2, 2% grade 3/4). Diarrhea (5% grade 2, 0% grade 3/4), nausea (0% grade 2‐4), and vomiting (0% grade 2‐4) were rare. CONCLUSIONS: Capecitabine administered for 7 days followed by a 7‐day rest in combination with bevacizumab had modest efficacy and an acceptable toxicity profile in patients with MBC. Gastrointestinal toxicity with this schedule was minimal. Cancer 2011;. © 2011 American Cancer Society. In this trial, the authors evaluated the efficacy and safety of a capecitabine schedule in combination with bevacizumab for the treatment of metastatic breast cancer. Capecitabine administered for 7 days followed by a 7‐day rest with bevacizumab had modest efficacy and an acceptable toxicity profile.