Clinical Phase I Study of TAS102/Irinotecan/Bevacizumab Combination Therapy in Japanese Patients With Unresectable Metastatic Colorectal Cancer (mCRC).

Background: In this phase I study, we aimed to examine the safety of a triple combination (TAS-102/irinotecan/bevacizumab) therapy in patients with previously treated metastatic colorectal cancer (mCRC).

Methods: In the TAS-102 dose-escalation phase, we determined dose-limiting toxicity (DLT), estimated the maximum tolerated dose (MTD), and determined the recommended dose (RD); in the expansion phase, we evaluated safety. The RD was administered in advance for 10 patients. The TAS-102 dose was increased to 25-35 mg/m and administered orally twice on days 1-5 and 8-12. Irinotecan (100 mg/m) and bevacizumab (5 mg/m) were administered on days 1 and 15 of the treatment, respectively.

Results: Fifteen patients were enrolled in dose-escalation Levels 1-3, and ten in the expansion phase. A 30 mg/m TAS-102 dose at Level 2 was administered to three patients, with one presenting grade 4 neutropenia. A 35 mg/m TAS-102 dose at Level 3 was administered to five patients, with three patients presenting grade 4 neutropenia and grade 3 DLTs. We added three patients at Level 2 and set the MTD at 30 mg/m, with no DLTs. The RD was fixed at 25 mg/m, with no DLTs (N = 10) or treatment-related deaths. One patient showed complete response at Level 2, four presented partial response, and eleven individuals maintained stable disease for over four months. The median progression-free survival duration was 7.6 months, while the median overall survival period was 16.9 months.

Conclusion: The TAS-102/irinotecan/bevacizumab combination therapy was safe, effective, and well-tolerated in patients previously treated with mCRC.