Response to regorafenib at an initial dose of 120 mg as salvage therapy for metastatic colorectal cancer.

Regorafenib (Reg) is an oral multikinase inhibitor that has achieved improved overall survival in patients with metastatic colorectal cancer (mCRC) in the salvage therapy setting. However, Reg is difficult to manage and determine the optimal dose due to adverse events (AEs). The objective of this study was to retrospectively evaluate the clinical benefit and determine the optimal dose of Reg in mCRC patients. A total of 20 mCRC patients were enrolled in this retrospective study. Initially, 8 patients who received a starting dose of 160 mg Reg (160 mg group) once a day were evaluated; however, they were unable to continue with the initial dose of 160 mg due to grade 3 adverse events (AEs), such as hand-foot skin reaction (HFSR) and small intestinal hemorrhage. Furthermore, 2 of the 8 patients refused subsequent treatment due to HFSR and the remaining 6 patients received a dose reduction from 160 to 120 mg Reg. A reduced dose of 120 mg Reg was also assessed with our dose modification method in 12 patients (120 mg group). The optimal response of the 160 and 120 mg group patients was 0.0 and 8.3% (1/12), respectively. In the 160 mg group, 3 patients exhibited stable disease (SD). Surprisingly, among the the 120 mg group patients 1 exhibited partial response (PR) and 6 had SD. The PR case displayed shrinkage of the local recurrence and morphological changes. One of the SD cases exhibited formation of a cavity in the lung metastasis, with intralesional morphological changes of the liver metastasis. The duration of the treatment in the PR case and the SD case with the cavitation was 6.5 months (9 cycles) and 5 months (6 cycles), respectively. The median progression-free survival (PFS) was 77 days (range, 30-230+ days) and the median overall survival (OS) was 204 days (range, 53-511+ days). The final date of the follow-up period was July 31, 2016. The 160 mg group was associated with a 25% (3/8) incidence of HFSR, 12.5% (1/8) of small intestinal hemorrhage and 12.5% (1/8) of anemia and thrombocytopenia; the AEs were grade >3. The 120 mg group was associated with an incidence of only 8.3% (1/12) of grade >3 hypertension. Thus, the 120 mg group experienced lower treatment-related toxicity compared with the 160 mg group. Despite a reduced initial dose of Reg, a significant effect was observed, with 1 PR and 6 favorable SD cases, with good tolerability. Therefore, an initial dose modification of 120 mg Reg is recommended as an alternative strategy for the treatment of mCRC in the salvage setting.