Rutaecarpine  the capecitabine–placebo arm had received anthracyclinecontaining therapy.The median duration of follow-up in the capecitabine cohort was 15.6 months. The study demonstrated a significant improvement in PFS with the capecitabine– bevacizumab combination compared with capecitabine– placebo.Despite AVF2119g not meeting its primary objective, the doubling of response rate provides an indication of activity and may be clinically meaningful to those patients. Additional important findings from the AVF2119g trial include the safety results. Although capecitabine was given at a dose higher than currently used in clinical practice, collection of chemotherapyrelated adverse events was more extensive than in RIBBON- 1 and therefore the trial provides a more thorough understanding of the safety profile of capecitabine–bevacizumab combination therapy.

In AVF2119g, the combination of bevacizumab with capecitabine had little impact on the  Sinomenine frequency or severity of capecitabinerelated adverse effects. In addition to the three randomised, phase III trials reported above,the literature includes several single- arm studies evaluating capecitabine–bevacizumab either alone or in combination with another chemotherapeutic agent. In the first-line setting, these studies include XCALIBr,North Central Cancer Treatment Group (NCCTG) NO43,an Italian phase II study of metronomic therapy with bevacizumab,and a subpopulation analysis of the ATHENA bevacizumab safety study.Further data on the combination of capecitabine and bevacizumab were generated in the ATHENA bevacizumab safety study. Although the primary aim of ATHENA was to evaluate bevacizumab in combination with first-line taxane-based therapy in routine oncology practice, investigators were permitted to combine bevacizumab with alternative standard first-line chemotherapy (excluding anthracyclines) if taxane therapy was not  purchase Apixaban considered their standard of care for a patient.

Assessment of outcome according to chemotherapy partner was prespecified in the statistical plan. Another group of Italian investigators evaluated an alternative triplet combination, opting for a low-dose metronomic schedule to overcome the considerable toxicity often associated with combination chemotherapy regimens. Metronomic chemotherapy appears to increase anti-angiogenic activity compared with cyclic order E7080 administration at higher doses. The combination of metronomic chemotherapy with anti-angiogenic agents has shown sustained tumour regression with no major toxicity in preclinical studies.There are several ongoing trials in MBC evaluating capecitabine–bevacizumab combination regimens, predominantly as first-line therapy, with or without additional chemotherapy.

In the first-line setting, the phase III capeciTabine and bevacizUmab Randomised against AvastiN anD taxOl Trial (TURANDOT) (ClinicalTrials. gov identifier NCT00600340) by the Central European Cooperative Oncology Group (CECOG) is comparing capecitabine–bevacizumab versus paclitaxel– bevacizumab in patients with HER2-negative MBC. The  regulates trial, now fully recruited, is aiming to address a question unanswered by RIBBON-1 by comparing different bevacizumab–chemotherapy combinations.