Salidroside objective of the TURANDOT trial is to demonstrate non-inferior overall survival with the capecitabine– bevacizumab combination regimen versus paclitaxel–bevacizumab, defined as an upper limit 61.33 for the two-sided CI for the overall survival hazard ratio. Secondary end-points include response rate PFS, time to response, duration of response, time to treatment failure, safety and quality of life. Recently reported interim data from 327 patients eligible for safety analysis revealed safety profiles consistent with those of the component agents.At the American Society of Clinical Oncology Annual Meeting 2011, the first data from a randomised trial evaluating a capecitabine- and bevacizumab-containing regimen in early breast cancer were reported from the National Surgical Adjuvant Breast and Bowel Project B-40 trial.The primary end-point was pCR rate.
Neither capecitabine nor gemcitabine increased the pCR rate or clinical response rate Ubiquinone when added to docetaxel, but both led to an increase in toxicity. The combination of capecitabine and bevacizumab is an active first-line regimen for patients with HER2-negative MBC, significantly improving PFS (the primary end-point) and response rate versus capecitabine–placebo. No significant difference in overall survival has been shown. Data from single-arm trials show similar efficacy, notwithstanding differences in patient characteristics between studies. The positive results from the RIBBON-1 trial contrast with the lack of PFS benefit seen in the AVF2119g trial in patients with heavily pretreated disease, supporting the widely accepted hypothesis that bevacizumab provides the greatest benefit when given early in the disease course before redundancy of purchase Oridonin anti-angiogenic pathways.
Numerous ongoing trials are evaluating capecitabine–bevacizumab combination therapy with or without a second chemotherapy agent (a taxane or vinorelbine). It remains to be seen whether any benefit in increased efficacy is outweighed by the likely increase in toxicity with a chemotherapy doublet. In June 2011, the European Commission approved order Diosmetin the combination of capecitabine and bevacizumab as first-line therapy for MBC, based on the results of the RIBBON-1 trial. This regimen provides an important treatment option for a subset of patients who are either unsuited to or prefer not to receive paclitaxel in combination with bevacizumab. Clinical trials of bevacizumab and capecitabine continue and should provide insight into currently unanswered questions, such as how to identify patients most likely to benefit from the capecitabine– bevacizumab combination and the optimal duration of therapy.
Although bevacizumab combined with taxane may be expected to provide a higher response rate than bevacizumab combined with capecitabine, for some patients, paclitaxel may not be the preferred therapy and the combination of bevacizumab–capecitabine is important. In addition, the lack of alopecia with capecitabine is a key consideration for regulates some patients. The TURANDOT trial is designed as a non-inferiority trial. If positive, it will indicate that capecitabine– bevacizumab provides a valid alternative to paclitaxel– bevacizumab, enabling physicians.