Randomised 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
Mené aux Pays-Bas sur 161 patients atteints d'un cancer colorectal métastatique, cet essai de phase III compare les effets, du point de vue de la survenue d'un syndrome pieds-mains, d'un composé appelé S-1, une fluoropyrimidine dispensée par voie orale, et de la capécitabine en traitement de première ligne
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 randomised 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 (RDI), progression-free survival (PFS), response rate (RR) and overall survival (OS). Results : A total of 161 patients were randomised in 27 centers. 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% vs 13%, p=0.03). Median RDI was 88% in the capecitabine group and 95% in the S-1 group (p=0.026). There were no statistically significant differences in median PFS, RR and OS rates. Conclusion : Treatment with S-1 in Western mCRC patients is associated with a significantly lower incidence of HFS compared to capecitabine, with comparable efficacy.