A novel capecitabine dosing schedule combined with bevacizumab is safe and active in patients with metastatic breast cancer: a phase II study.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #6121 Background Capecitabine (Xeloda®,C) has activity in breast cancer when dosed for 14 days (d) followed by a 7d rest (14 - 7). Using mathematical methods, we predict the optimal dosing schedule of C to be 7d followed by a 7d rest (7 - 7) (Norton et al, AACR 2005). Xenograft studies show this schedule improves tolerability and survival. The MTD of C(7 - 7) is higher than that for conventional dosing (Traina et al, JCO 2008). Bevacizumab (B), an anti-VEGF antibody, improves response when added to capecitabine in pts previously treated for metastatic disease (Miller et al, JCO) and improves PFS when added to taxanes in the 1st-line treatment of advanced disease (Miller et al, NEJM 2007; Miles ASCO 2008). B + conventionally-dosed capecitabine modestly increased TTP when used as 1st-line therapy (Sledge, ASCO 2007). This study tests C(7 - 7) with bevacizumab (B) in a Phase II trial. Methods Eligible patients (pts) have measurable, metastatic breast cancer (MBC), ECOG performance status (PS) ≤2 and normal organ function. Any number of prior chemotherapy (CRx) regimens is permitted. Pts with prior fluoropyrimidine or bevacizumab are excluded. Therapy (tx) consists of C (2,000mg BID, 7 - 7) and B (10mg/kg IV q2 weeks(wk)). Pts are evaluated for toxicity q2wk and for response q12wk. Cycle length: 4 wks. Primary endpoint: response rate (RR). Secondary endpoints: clinical benefit, TTP, PFS, toxicity. Using a mini-max, two-stage design, up to 40 patients will be enrolled. If >6/40 pts respond, then C(7 - 7) + B will be considered worthy of further study. If >11 pts experience Grade 3/4 capecitabine-related toxicity the trial will be stopped. Results Twenty-seven pts are enrolled. Median (med) age 57 yrs (29-71), med ECOG performance status 0 (0-2), ER/PR(+) 13, HER2(+) 1, sites of MBC: bone(13), liver/lung(13), soft tissue(12). Prior tx: Adjuvant: CRx (20), hormone tx (14); MBC: CRx (2), hormone tx (16). 27 pts are evaluable for toxicity. After a med of 6 (1-12) cycles: Twenty-three pts evaluable for response: PR=7 (confirmed=5), stable disease (SD) >6 mo =6, SD<6 mo=7, PD=3.Tx-related toxicity (# Gr 3/Gr 2): hand foot syndrome (HFS) (6/9); diarrhea (0/1); hypertension (2/1), proteinuria (0/0). 1 pt had grade 4 pulmonary embolism requiring discontinuation of B. Conclusions Combination capecitabine (7 - 7) and bevacizumab appears well tolerated and active. Additional safety and efficacy data is anticipated prior to this meeting. Supported in part by Roche and Genentech. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6121.