Eiji Oki1, Akitaka Makiyama2,3, Yuji Miyamoto4, Masahiko Kotaka5, Hirofumi Kawanaka6, Keisuke Miwa7, Akira Kabashima8, Tomohiro Noguchi9, Kotaro Yuge10, Tomomi Kashiwada11, Koji Ando1, Mototsugu Shimokawa12, Hiroshi Saeki13, Yoshito Akagi7, Hideo Baba4, Yoshihiko Maehara14, Masaki Mori1. 1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 2. Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, Kitakyushu, Japan. 3. Cancer Center, Gifu University Hospital, Gifu, Japan. 4. Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medicine, Kumamoto, Japan. 5. Gastrointestinal Cancer Center, Sano Hospital, Kobe, Japan. 6. Department of Surgery, National Hospital Organization Beppu Medical Center, Beppu, Japan. 7. Department of Surgery, Kurume University Hospital, Kurume, Japan. 8. Department of Surgery, National Hospital Organization Oita Medical Center, Oita, Japan. 9. Department of Surgery, Imakiire General Hospital, Kagoshima, Japan. 10. Department of Surgery, Social Insurance Tagawa Hospital, Tagawa, Japan. 11. Department of Internal Medicine, Division of Hematology, Respiratory Medicine and Oncology, Faculty of Medicine, Saga University, Saga, Japan. 12. Department of Biostatistics, Yamaguchi University, Yamaguchi, Japan. 13. Department of Gastroenterological Surgery, Gunma University Graduate School of Medicine, Maebashi, Japan. 14. Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan.
Abstract
BACKGROUND: A previous Phase I/II study demonstrated that TAS-102 (trifluridine/tipiracil [FTD/TPI]) plus bevacizumab (Bev) has encouraging efficacy and controllable safety for patients with previously treated metastatic colorectal cancer. Therefore, we designed for assessing the efficacy and safety of FTD/TPI plus Bev in elderly patients with previously untreated metastatic colorectal cancer. METHODS: This is a multicenter, single-arm Phase II study included patients ≥70 years old with previously untreated, unresectable metastatic colorectal cancer. Treatment consisted of FTD/TPI plus Bev given every 4 weeks. The primary endpoint was progression-free survival (PFS), assuming a null hypothesis of a PFS of 5 months. The secondary endpoints were the overall survival (OS), overall response rate (ORR), and adverse events (AEs). RESULTS: Between 5 January 2017 and 13 March 2018, 39 patients were enrolled from 18 institutions. The median patient age was 76.0 years (range, 70-88); the ECOG-PS was 0 in 24 patients and 1 in 15 patients. The median PFS was 9.4 months as a primary endpoint, and the median OS was 22.4 months. The ORR was 40.5% and the disease control rate was 86.5%. Grade 3-4 AEs included neutropenia (71.8%), leukopenia (51.3%), anorexia (15.4%), febrile neutropenia (10.3%), and fatigue (10.3%). CONCLUSIONS: FTD/TPI plus Bev is an effective and well-tolerated regimen for elderly patients with previously untreated metastatic colorectal cancer. Capecitabine/bevacizumab can be selected as a subsequent maintenance therapy without irinotecan and oxaliplatin because FTD/TPI has no cross-resistance with 5-fluorouracil. CLINICAL TRIAL REGISTRATION: UMIN clinical trials registry (UMIN000025241).
BACKGROUND: A previous Phase I/II study demonstrated that TAS-102 (trifluridine/tipiracil [FTD/TPI]) plus bevacizumab (Bev) has encouraging efficacy and controllable safety for patients with previously treated metastatic colorectal cancer. Therefore, we designed for assessing the efficacy and safety of FTD/TPI plus Bev in elderly patients with previously untreated metastatic colorectal cancer. METHODS: This is a multicenter, single-arm Phase II study included patients ≥70 years old with previously untreated, unresectable metastatic colorectal cancer. Treatment consisted of FTD/TPI plus Bev given every 4 weeks. The primary endpoint was progression-free survival (PFS), assuming a null hypothesis of a PFS of 5 months. The secondary endpoints were the overall survival (OS), overall response rate (ORR), and adverse events (AEs). RESULTS: Between 5 January 2017 and 13 March 2018, 39 patients were enrolled from 18 institutions. The median patient age was 76.0 years (range, 70-88); the ECOG-PS was 0 in 24 patients and 1 in 15 patients. The median PFS was 9.4 months as a primary endpoint, and the median OS was 22.4 months. The ORR was 40.5% and the disease control rate was 86.5%. Grade 3-4 AEs included neutropenia (71.8%), leukopenia (51.3%), anorexia (15.4%), febrile neutropenia (10.3%), and fatigue (10.3%). CONCLUSIONS:FTD/TPI plus Bev is an effective and well-tolerated regimen for elderly patients with previously untreated metastatic colorectal cancer. Capecitabine/bevacizumab can be selected as a subsequent maintenance therapy without irinotecan and oxaliplatin because FTD/TPI has no cross-resistance with 5-fluorouracil. CLINICAL TRIAL REGISTRATION: UMIN clinical trials registry (UMIN000025241).
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Authors: G Sommerhäuser; A Kurreck; S Stintzing; V Heinemann; L Fischer von Weikersthal; T Dechow; F Kaiser; M Karthaus; I Schwaner; M Fuchs; A König; C Roderburg; I Hoyer; M Quante; A Kiani; S Fruehauf; L Müller; A Reinacher-Schick; T J Ettrich; A Stahler; D P Modest Journal: BMC Cancer Date: 2022-07-27 Impact factor: 4.638