TAS-102 Safety in Metastatic Colorectal Cancer: Results From the First Postmarketing Surveillance Study

To our knowledge, this study is the first report on adverse drug reactions and safety profile of TAS-102 for metastatic colorectal cancer in clinical practice. Serious neutropenia and febrile neutropenia (FN) tended to occur from days 15 to 21 in the first cycle. Careful monitoring of patients with serious neutropenia around day 15 in the first cycle should be done to prevent FN. Background: Unexpected toxicities of newly approved drugs might be revealed in clinical practice after market launch. This postmarketing surveillance study investigated expected and unexpected adverse drug reactions (ADRs) of TAS-102 in clinical practice in the first 6 months after market launch. Patients and Methods: All metastatic colorectal cancer (mCRC) patients (pts) received TAS-102 35 mg/m(2) as a starting dose orally twice daily for 5 consecutive days, with 2 days of rest per week for 2 weeks, followed by a 14-day rest period. ADRs during treatment courses were reported spontaneously by attending physicians. Results: From May 26 to November 25, 2014, 3420 mCRC pts were treated with TAS-102 at 1134 institutes in Japan. In total, 370 ADRs (185 ADRs of myelosuppression and related infection in 125 pts, of which 58 ADRs in 31 pts were serious ADRs [ SADRs] and 127 ADRs in 98 pts were non-SADRs) were observed in 219 pts and included 89 SADRs in 51 pts and 281 non-SADRs in 183 pts (a pt was counted twice if SADR and non-SADR were experienced). The most frequent ADRs were: myelosuppression comprising neutropenia (n = 77), leukopenia (n = 28), thrombocytopenia (n = 23), anemia (n = 20), and febrile neutropenia (FN; n = 19). Serious neutropenia and FN tended to occur from days 15 to 21 in the first cycle in 12 (75%) of 16 pts. Conclusion: The ADRs and safety profile of TAS-102 in this study was similar to that in recent TAS-102 clinical trials, without unexpected safety signals. Careful monitoring should be undertaken in pts with serious neutropenia around day 15 in the first cycle of treatment to prevent FN.