as combined with a taxane or anthracycline based combination therapy in one cohort or with capecitabine in a second cohort. This trial is discussed in more detail later. For patients who are ineligible for paclitaxel based regimens or who prefer not to receive Bay 43-9006 paclitaxel therapy for MBC, the combination of bevacizumab with nontaxane Silodosin Rapaflo chemotherapy is of interest. Capecitabine is an attractive treatment choice for patients who have shown disease progression following taxane therapy, who are unwilling to receive further taxane treatment after previous experience in the adjuvant setting, who will not accept specific side effects of taxane based therapy, such as hair loss or neuropathy, or who have comorbidities that may predispose them to neuropathy.
There are both preclinical Bicalutamide Cosudex and practical reasons for combining bevacizumab and capecitabine. In xenograft models, the combination demonstrated a synergistic inhibitory effect on tumour growth and a significant survival benefit.16 There was no evidence that this synergy resulted from upregulation of thymidine phosphorylase, the key enzyme in the activation of capecitabine, instead the synergy appears to be attributable to the combination of anti angiogenic and cytotoxic mechanisms of action. 2. Capecitabine bevacizumab combination therapy for MBC 2.1. Randomised phase III trials The most robust evidence of the efficacy of capecitabine and bevacizumab combination therapy in MBC comes from the RIBBON 1 trial mentioned briefly above.15 This randomised phase III trial was conducted in 1237 patients with HER2 negative MBC who had received no prior chemotherapy for metastatic disease.
Investigators declared their planned chemotherapy regimen for each patient. Patients were then randomised in a 2:1 ratio to receive either bevacizumab or placebo in combination with the selected chemotherapy. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent. At disease progression, all patients were able to receive bevacizumab in combination buy Daptomycin with their second line chemotherapy. Importantly, the two cohorts were independently powered and analysed and thus RIBBON 1 was essentially two parallel trials. This trial design has important implications for interpretation: because investigators were able to choose whether patients received capecitabine, taxane or anthracycline regimens, there were marked differences in baseline characteristics between the populations.
Therefore it is not appropriate to compare the results between different chemotherapy cohorts and in this summary we will focus on the cohort of patients who received capecitabine with either bevacizumab or placebo. The baseline characteristics were well balanced between the two treatment arms of the problem solving capecitabine cohort in RIBBON 1. The median age was 56 years in the capecitabine bevacizumab treatment arm and 57 years in the capecitabine placebo arm. Almost one quarter of the patients had triple negative disease and approximately one quarter had a disease free interval 612 months. The majority of patients had received adjuvant chemotherapy. Approximately 40% of patients in each arm had received previous taxane containing regimens, and 60% of the capecitabine bevacizumab arm and 69% of the capecitabine placebo.