BackgroundRegorafenib and its metabolites may inhibit the activities of several CYP or UDP-glucuronosyltransferase isoforms, including that of CYP2C9. Therefore, pharmacological agents that are CYP2C9 substrates may show elevated circulating levels and enhanced drug efficacy when concurrently used with regorafenib. Previous studies showed that the area under the plasma concentration-time curve of warfarin, which is the substrate for CYP2C9, increased upon co-administration of regorafenib. However, there are no reports indicating that the anticoagulant effects of warfarin increased upon co-administration of regorafenib.Case presentationWe report a case of a 76-year-old man with liver metastasis of colon cancer. He was treated with regorafenib at a dosage of 120 mg daily on days 1 to 21 every 4 weeks as a third-line therapy. He had a history of acute myocardial infarction and had taken 2 mg warfarin daily. Three weeks after the treatment began, PT/INR values markedly increased, although there was no hemorrhage. Administration of regorafenib and warfarin was discontinued, and then PT/INR rapidly decreased. Warfarin administration was restarted (0.5 mg daily) and the dose was increased up to 1.5 mg daily. The patient’s PT/INR values exhibited a tendency to increase when concurrently used with regorafenib, the dose of which was reduced to 80 mg daily on days 1 to 14 every 3 weeks at a physician's discretion.ConclusionsThe clinical course of this patient suggested that PT/INR might increase during concurrent use of warfarin and regorafenib. Therefore, PT/INR should be periodically monitored during the concurrent use of warfarin and regorafenib.

Molecular targeted drugs, such as everolimus and sunitinib, have shown efficacy against advanced pancreatic neuroendocrine tumors. Octreotide, a somatostatin analogue, improves the hormone-related symptoms in patients with neuroendocrine tumors. Furthermore, it has been reported that octreotide has antitumor activity in patients with metastatic midgut neuroendocrine tumors. However, whether octreotide has anti-proliferative effects in patients with advanced pancreatic neuroendocrine tumors is not fully understood. We report a 71-year-old man with multiple liver metastases of pancreatic neuroendocrine tumor. He was treated with everolimus 10 mg daily and sunitinib 25 mg daily on days 1-14 every 3 weeks at the physician's discretion. However, these molecular targeted drugs were discontinued due to disease progression or severe adverse effects. Octreotide long-acting repeatable was administered continuously from the initiation of everolimus treatment. The tumor marker level markedly decreased and the metastatic liver lesions showed shrinkage with octreotide treatment. Immunohistochemistry of tumor specimens obtained before treatment showed that somatostatin receptor 2, a high-affinity receptor for octreotide, was highly expressed. The clinical course of this patient suggested that octreotide long-acting repeatable may be a treatment option for advanced pancreatic neuroendocrine tumors after failure of everolimus and sunitinib. Further clinical trials are warranted to determine whether the expression of somatostatin receptor 2 in tumor tissues is predictive of octreotide efficacy.