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

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. 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). 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. 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.

Gajria D ，Feigin K ，Tan LK ，Patil S ，Geneus S ，Theodoulou M ，Norton L ，Hudis CA ，Traina TA ... -  《-》

Phase II trial of a novel capecitabine dosing schedule in combination with lapatinib for the treatment of patients with HER2-positive metastatic breast cancer.

Gajria D ，Gonzalez J ，Feigin K ，Patil S ，Chen C ，Theodoulou M ，Drullinsky P ，D'Andrea G ，Lake D ，Norton L ，Hudis CA ，Traina TA ... -  《-》

The Breast Avastin Trial: phase II study of bevacizumab maintenance therapy after induction chemotherapy with docetaxel and capecitabine for the first-line treatment of patients with locally recurrent or metastatic breast cancer.

Bisagni G ，Musolino A ，Panebianco M ，De Matteis A ，Nuzzo F ，Ardizzoni A ，Gori S ，Gamucci T ，Passalacqua R ，Gnoni R ，Moretti G ，Boni C ... -  《-》

Phase II study of oral vinorelbine in combination with capecitabine as second line chemotherapy in metastatic breast cancer patients previously treated with anthracyclines and taxanes.

Jones A ，O'Brien M ，Sommer H ，Nowara E ，Welt A ，Pienkowski T ，Rolski J ，Pham ML ，Perraud K ，Trillet-Lenoir V ... -  《-》

Concurrent bevacizumab with a sequential regimen of doxorubicin and cyclophosphamide followed by docetaxel and capecitabine as neoadjuvant therapy for HER2- locally advanced breast cancer: a phase II trial of the NSABP Foundation Research Group.

Bevacizumab with chemotherapy improves outcomes in patients with metastatic breast cancer (MBC). The purpose of this trial was to determine the activity and safety profile of neoadjuvant bevacizumab with chemotherapy in women with locally advanced breast cancer (LABC). Between November 2006 and August 2007, 45 women with HER2(-) LABC began preoperative standard AC (doxorubicin [Adriamycin], cyclophosphamide) × 4 cycles followed by docetaxel 75 mg/m(2) intravenously (I.V.) on day 1 and capecitabine 825 mg/m(2) twice daily on days 1-14 (TX, docetaxel [Taxotere] and capecitabine [Xeloda]) every 21 days for 4 cycles. Bevacizumab 15 mg/kg I.V. was given concurrently with chemotherapy every 21 days for a total of 6 preoperative doses. Postoperatively bevacizumab was resumed for a total of 10 doses. The primary endpoint was pathologic complete response (pCR) in the breast. Thirty patients (66.7%) had stage IIIA disease, 12 (26.7%) patients had stage IIIB, and 3 patients (6.7%) had stage IIIC. Of these, 10 (22%) had inflammatory breast cancer (IBC), and 27 (60%) had estrogen receptor (ER)(+) disease. A pCR in the breast with negative axillary nodes was documented in 4 (9%) of 45 patients. Toxicities that were seen with AC and bevacizumab included fatigue (grade 2/3; 31% and 9%, respectively), mucositis (grade 2/3; 29% and 2%, respectively), and headache (grade 2/3; 16% and 7%, respectively). Toxicities seen with TX and bevacizumab included mucositis (grade 2/3; 48% and 25%, respectively), fatigue (grade 2/3; 43% and 18%, respectively), and hand-foot syndrome (grade 2/3; 34% and 23%, respectively). This regimen demonstrated only modest activity with substantial toxicity and does not appear to warrant further evaluation.

Rastogi P ，Buyse ME ，Swain SM ，Jacobs SA ，Robidoux A ，Liepman MK ，Pajon ER ，Dy PA ，Posada JG Jr ，Melnik MK ，Piette F ，Geyer CE Jr ，Mamounas EP ，Wolmark N ... -  《-》