Regorafenib, Free Base

Soluble in DMSO. Regorafenib demonstrated tolerability and antitumour activity in patients with metastatic colorectal cancer (CRC) in a phase 1 clinical trail. Strumberg D., et al. 'Regorafenib (BAY 73-4506) in advanced colorectal cancer: a phase I study.' Br. J. Cancer 106: 1722-1727 (2012). In combination chemotherapy, regorafenib showed acceptable tolerability with SN-38 and irinotecan but showed no significant effect on oxaliplatin or 5-fluorouracil pharmacokinetics. Schultheis B., et al. 'Regorafenib in combination with FOLFOX or FOLFIRI as first- or second-line treatment of colorectal cancer: results of a multicenter, phase Ib study.' Ann. Oncol. 24: 1560-1567 (2013). Regorafenib showed significant activity in patients with advanced and metastatic GI stromal tumor (GIST) after failure of both imatinib and sunitinib in a phase 2 clinical trial. George S., et al. 'Efficacy and safety of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of imatinib and sunitinib: a multicenter phase II trial.' J. Clin. Oncol. 30: 2401-2407 (2012). In a phase 2 clinical trial, regorafenib demonstrated acceptable tolerability and antitumour activity in patients with intermediate or advanced hepatocellular carcinoma (HCC) after failure of first-line sorafenib. Bruix J., et al. 'Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: Multicentre, open-label, phase II safety study.' Eur. J. Cancer 49: 3412-3419 (2013). In a phase 3 study, regorafenib demonstrated prolonged survival of patients with metastatic colorectal cancer after standard therapies failed. Grothey A., et al. 'Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial.' Lancet 381: 303-312 (2013). Regorafenib demonstrated antitumour activity as a first-line treatment for metastatic or unresectable renal-cell carcinoma in a phase 2 clinical trial. However, the drug's safety profile required close monitoring. Eisen T., et al. 'Regorafenib for patients with previously untreated metastatic or unresectable renal-cell carcinoma: a single-group phase 2 trial.' Lancet Oncol. 13: 1055-1062 (2012). Oral regorafenib significantly improved progression-free survival when compared with placebo in patients with metastatic gastrointestinal stromal tumours (GIST) after failure of standard treatments in a phase 3 clinical trial. Demetri G.D., et al. 'Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial.' Lancet 381: 295-302 (2013).