Other treatment-related adverse events leading to regorafenib discontinuation included hypertension, fatigue, thrombocytopenia and diarrhea. Among 25 patients treated at 160 mg dose level, 6 patients permanently

discontinued due to treatment-related adverse events including hand-foot skin reaction, hypertension, fatigue, thrombocytopenia and duodenal ulcer. In efficacy evaluation, 27 evaluable patients achieved 74% disease control rate with partial response in 1 patient (4%) and stable disease in 19 patients (70%). Overall, regorafenib was well tolerated and adverse events were manageable (59). The multi-national phase III CORRECT trial enrolled mCRC patients who Inhibitors,research,lifescience,medical had received all locally-approved Inhibitors,research,lifescience,medical standard therapies and had progressed during or within 3 months after the last standard therapy (10). Patients were randomized in a 2:1 ratio to receive regorafenib

or placebo. 500 patients received regorafenib at 160 mg orally 21 days on 7 days off and 253 patients received placebo. Median OS was 6.4 months in the regorafenib group versus 5.0 months in the placebo group (HR 0.77; 95% CI: 0.64-0.94; one-sided P=0.0052). Similar clinical benefit was observed in patient with colon cancer and rectal. The most common treatment-related Grade 3 or worse adverse events were Inhibitors,research,lifescience,medical hand-foot skin reaction (17%), fatigue (10%), diarrhea (7%), hypertension (7%), and rash or skin desquamation (6%), consistent with that observed in earlier phase trials. These adverse events were mostly manageable with dose reduction or interruption. Conclusion Angiogenesis is now a validated therapeutic target in CRC patients with macroscopic metastases. Recent development added 2 new anti-angiogenic drugs to the CRC Inhibitors,research,lifescience,medical treatment armamentarium and confirmed the advantage of

continuing angiogenic suppression beyond first progression in metastatic CRC patients (60). Evidence so far supports the use of bevacizumab in both first- and second-line treatment of metastatic CRC patients. In comparison, the role of aflibercept Inhibitors,research,lifescience,medical in these settings remains unclear given the comparable efficacy but higher cost compared to bevacizumab. Aflibercept targets a broader set of pro-angiogenic growth factors than bevacizumab, and has the theoretical advantage of more effective angiogenic suppression and overcoming bevacizumab resistance. However, these hypotheses Dacomitinib are yet to be confirmed in clinical studies. As the chemotherapeutic options and supportive care improve, more metastatic CRC patients nowadays have good performance status by the time they exhausted all standard therapy. For them, regorafenib is a welcomed option in addition to participation in clinical trials. Looking back, the overall survival of patients with metastatic CRC has increased several folds when compared to decades ago even though, it seemed, each drug achieved only incremental improvement individually. However, it is clear more novel treatment approaches are needed to continue this trend.