J J M Kwakman1, L H J Simkens2, J M van Rooijen3, A J van de Wouw4, A J Ten Tije5, G J M Creemers6, M P Hendriks7, M Los8, R J van Alphen9, M B Polée10, E W Muller11, A M T van der Velden12, T van Voorthuizen13, M Koopman14, L Mol15, E van Werkhoven16, C J A Punt1. 1. Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam. 2. Department of Medical Oncology, Maxima Medical Center, Eindhoven. 3. Department of Medical Oncology, Martini Hospital, Groningen. 4. Department of Medical Oncology, VieCuri Medical Center, Venlo. 5. Department of Medical Oncology, Amphia Hospital, Breda. 6. Department of Medical Oncology, Catharina Hospital, Eindhoven. 7. Department of Medical Oncology, Northwest Clinics, Alkmaar. 8. Department of Medical Oncology, Sint Antonius Hospital, Nieuwegein. 9. Department of Medical Oncology, TweeSteden Hospital, Tilburg. 10. Department of Medical Oncology, Medical Center Leeuwarden, Leeuwarden. 11. Department of Medical Oncology, Slingeland Hospital, Doetinchem. 12. Department of Medical Oncology, Tergooi Hospital, Hilversum. 13. Department of Medical Oncology, Rijnstate Hospital, Arnhem. 14. Department of Medical Oncology, University Medical Center Utrecht, University Utrecht, Utrecht. 15. Clinical Trial Department, Netherlands Comprehensive Cancer Organisation (IKNL), Nijmegen. 16. Department of Biometrics, The Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands.
Abstract
BACKGROUND: Hand-foot syndrome (HFS) is a common side-effect of capecitabine. S-1 is an oral fluoropyrimidine with comparable efficacy to capecitabine in gastrointestinal cancers but associated with a lower incidence of HFS in Asian patients. This study compares the incidence of HFS between S-1 and capecitabine as first-line treatment in Western metastatic colorectal cancer (mCRC) patients. PATIENTS AND METHODS: Patients with previously untreated mCRC and planned treatment with fluoropyrimidine monochemotherapy were randomized 1 : 1 to receive either capecitabine (1250 mg/m2 orally for patients <70 years; 1000 mg/m2 for patients ≥70 years, twice daily on days 1-14) or S-1 (30 mg/m2 orally twice daily on days 1-14) in 3-weekly cycles, with bevacizumab optional in both groups. The primary endpoint was the incidence of any grade HFS, as assessed by both physicians and patients (diaries). Secondary endpoints included grade 3 HFS, other toxicities, relative dose intensity, progression-free survival, response rate and overall survival. RESULTS: A total of 161 patients were randomized in 27 centres. The incidence of any grade HFS as assessed by physicians was 73% in the capecitabine group (n = 80) and 45% in the S-1 group (n = 80) [odds ratio (95% confidence interval) 0.31 (0.16-0.60), P = 0.0005]. The incidence of grade 3 HFS was 21% and 4% (P = 0.003), respectively. Patient-assessed any grade HFS was 84% and 58%, respectively (P = 0.004). Grade 3 anorexia was more common in the S-1 group (3% versus 13%, P = 0.03). Median relative dose intensity was 88% in the capecitabine group and 95% in the S-1 group (P = 0.026). There were no statistically significant differences in median progression-free survival, response rate and overall survival rates. CONCLUSION: Treatment with S-1 in Western mCRC patients is associated with a significantly lower incidence of HFS compared with capecitabine, with comparable efficacy. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT01918852.
BACKGROUND: Hand-foot syndrome (HFS) is a common side-effect of capecitabine. S-1 is an oral fluoropyrimidine with comparable efficacy to capecitabine in gastrointestinal cancers but associated with a lower incidence of HFS in Asian patients. This study compares the incidence of HFS between S-1 and capecitabine as first-line treatment in Western metastatic colorectal cancer (mCRC) patients. PATIENTS AND METHODS: Patients with previously untreated mCRC and planned treatment with fluoropyrimidine monochemotherapy were randomized 1 : 1 to receive either capecitabine (1250 mg/m2 orally for patients <70 years; 1000 mg/m2 for patients ≥70 years, twice daily on days 1-14) or S-1 (30 mg/m2 orally twice daily on days 1-14) in 3-weekly cycles, with bevacizumab optional in both groups. The primary endpoint was the incidence of any grade HFS, as assessed by both physicians and patients (diaries). Secondary endpoints included grade 3 HFS, other toxicities, relative dose intensity, progression-free survival, response rate and overall survival. RESULTS: A total of 161 patients were randomized in 27 centres. The incidence of any grade HFS as assessed by physicians was 73% in the capecitabine group (n = 80) and 45% in the S-1 group (n = 80) [odds ratio (95% confidence interval) 0.31 (0.16-0.60), P = 0.0005]. The incidence of grade 3 HFS was 21% and 4% (P = 0.003), respectively. Patient-assessed any grade HFS was 84% and 58%, respectively (P = 0.004). Grade 3 anorexia was more common in the S-1 group (3% versus 13%, P = 0.03). Median relative dose intensity was 88% in the capecitabine group and 95% in the S-1 group (P = 0.026). There were no statistically significant differences in median progression-free survival, response rate and overall survival rates. CONCLUSION: Treatment with S-1 in Western mCRC patients is associated with a significantly lower incidence of HFS compared with capecitabine, with comparable efficacy. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT01918852.
Authors: Emil Ter Veer; Lok Lam Ngai; Gert van Valkenhoef; Nadia Haj Mohammad; Maarten C J Anderegg; Martijn G H van Oijen; Hanneke W M van Laarhoven Journal: Sci Rep Date: 2017-08-02 Impact factor: 4.379