Randomized phase III trial of S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer: SALTO study by the Dutch Colorectal Cancer Group

J. J. M. Kwakman; L. H. J. Simkens; J. M. van Rooijen; A. J. van de Wouw; A. J. ten Tije; G. J. M. Creemers; M. P. Hendriks; M. Los; R. J. van Alphen; M. B. Polée; E. W. Muller; A. M. T. van der Velden; T. van Voorthuizen; M. Koopman; L. Mol; E. van Werkhoven; C. J. A. Punt

doi:https://doi.org/10.1093/annonc/mdx122

Randomized phase III trial of S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer: SALTO study by the Dutch Colorectal Cancer Group

J. J. M. Kwakman, L. H. J. Simkens, J. M. van Rooijen, A. J. van de Wouw, A. J. ten Tije, G. J. M. Creemers, M. P. Hendriks, M. Los, R. J. van Alphen, M. B. Polée, E. W. Muller, A. M. T. van der Velden, T. van Voorthuizen, M. Koopman, L. Mol, E. van Werkhoven, C. J. A. Punt

Research output: Contribution to journal › Article › Academic › peer-review

52 Citations (Scopus)

Abstract

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 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. 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. Treatment with S-1 in Western mCRC patients is associated with a significantly lower incidence of HFS compared with capecitabine, with comparable efficacy. NCT01918852

Original language	English
Pages (from-to)	1288-1293
Journal	Annals of Oncology
Volume	28
Issue number	6
Early online date	2017
DOIs	https://doi.org/10.1093/annonc/mdx122
Publication status	Published - 2017

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Kwakman, J. J. M., Simkens, L. H. J., van Rooijen, J. M., van de Wouw, A. J., ten Tije, A. J., Creemers, G. J. M., Hendriks, M. P., Los, M., van Alphen, R. J., Polée, M. B., Muller, E. W., van der Velden, A. M. T., van Voorthuizen, T., Koopman, M., Mol, L., van Werkhoven, E., & Punt, C. J. A. (2017). Randomized phase III trial of S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer: SALTO study by the Dutch Colorectal Cancer Group. Annals of Oncology, 28(6), 1288-1293. https://doi.org/10.1093/annonc/mdx122

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title = "Randomized phase III trial of S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer: SALTO study by the Dutch Colorectal Cancer Group",

abstract = "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 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. 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. Treatment with S-1 in Western mCRC patients is associated with a significantly lower incidence of HFS compared with capecitabine, with comparable efficacy. NCT01918852",

author = "Kwakman, {J. J. M.} and Simkens, {L. H. J.} and {van Rooijen}, {J. M.} and {van de Wouw}, {A. J.} and {ten Tije}, {A. J.} and Creemers, {G. J. M.} and Hendriks, {M. P.} and M. Los and {van Alphen}, {R. J.} and Pol{\'e}e, {M. B.} and Muller, {E. W.} and {van der Velden}, {A. M. T.} and {van Voorthuizen}, T. and M. Koopman and L. Mol and {van Werkhoven}, E. and Punt, {C. J. A.}",

year = "2017",

doi = "https://doi.org/10.1093/annonc/mdx122",

language = "English",

volume = "28",

pages = "1288--1293",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Oxford University Press",

number = "6",

}

Kwakman, JJM, Simkens, LHJ, van Rooijen, JM, van de Wouw, AJ, ten Tije, AJ, Creemers, GJM, Hendriks, MP, Los, M, van Alphen, RJ, Polée, MB, Muller, EW, van der Velden, AMT, van Voorthuizen, T, Koopman, M, Mol, L, van Werkhoven, E & Punt, CJA 2017, 'Randomized phase III trial of S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer: SALTO study by the Dutch Colorectal Cancer Group', Annals of Oncology, vol. 28, no. 6, pp. 1288-1293. https://doi.org/10.1093/annonc/mdx122

Randomized phase III trial of S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer: SALTO study by the Dutch Colorectal Cancer Group. / Kwakman, J. J. M.; Simkens, L. H. J.; van Rooijen, J. M. et al.
In: Annals of Oncology, Vol. 28, No. 6, 2017, p. 1288-1293.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Randomized phase III trial of S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer: SALTO study by the Dutch Colorectal Cancer Group

AU - Kwakman, J. J. M.

AU - Simkens, L. H. J.

AU - van Rooijen, J. M.

AU - van de Wouw, A. J.

AU - ten Tije, A. J.

AU - Creemers, G. J. M.

AU - Hendriks, M. P.

AU - Los, M.

AU - van Alphen, R. J.

AU - Polée, M. B.

AU - Muller, E. W.

AU - van der Velden, A. M. T.

AU - van Voorthuizen, T.

AU - Koopman, M.

AU - Mol, L.

AU - van Werkhoven, E.

AU - Punt, C. J. A.

PY - 2017

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N2 - 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 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. 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. Treatment with S-1 in Western mCRC patients is associated with a significantly lower incidence of HFS compared with capecitabine, with comparable efficacy. NCT01918852

AB - 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 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. 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. Treatment with S-1 in Western mCRC patients is associated with a significantly lower incidence of HFS compared with capecitabine, with comparable efficacy. NCT01918852

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DO - https://doi.org/10.1093/annonc/mdx122

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