AT ECCO2017
AMSTERDAM (FRONTLINE MEDICAL NEWS) – For patients with metastatic colorectal cancer, S-1 was comparable in efficacy to capecitabine (Xeloda), and was associated with a lower incidence of all grades of hand-foot syndrome, reported investigators.
Among 161 patients with untreated metastatic colorectal cancer, the investigator-assessed incidence of all grades of hand-foot syndrome was 73% for patients randomly assigned to capecitabine, compared with 45% for patients randomized to S-1 (P = .0005).
Patient-assessed symptoms also were lower with S-1 than with capecitabine, reported Robert Jan Kwakman, MD, of the Academic Medical Center in Amsterdam.
“We conclude that treatment with S-1 is a useful alternative to capecitabine in the treatment of metastatic colorectal cancer,” he said at an annual congress sponsored by the European Cancer Organisation.
S-1 is an oral fluoropyrimidine consisting of tegafur, a prodrug of 5-fluorauracil (5-FU), combined with two 5-FU biochemical modulators. It is associated with a lower incidence of hand-foot syndrome than capecitabine, and has shown efficacy comparable to that of other fluoropyrimidines in Asian patients with gastrointestinal cancers, Dr. Kwakman noted.
Hand-foot syndrome can vary in severity from grade 1, marked by minimal skin changes or dermatitis without pain, to grade 3, characterized by severe skin changes with pain and significant limits to self care during activities of daily living.
In the randomized phase III SALTO trial (S1 Versus Capecitabine in the First Line Treatment of Metastatic Colorectal Cancer Patients), investigators in the Dutch Colorectal Cancer Group enrolled patients with untreated metastatic colorectal cancer with World Health Organization performance status 0-2 who were scheduled for treatment with fluoropyrimidine monotherapy. The patients were assigned to receive either capecitabine 1,250 mg/m2 for patients younger than 70, or 1,000 mg/m2 for those 70 and older, twice a day for days 1-14 of a 3-week cycle, or to S-1 30 mg/m2 twice daily on the same schedule.
In each arm, investigators could, at their discretion, also prescribe bevacizumab 7.5 mg/kg on day 1. In each arm, 59% of patients were scheduled to receive bevacizumab.
Patients were stratified by bevacizumab status, lactate dehydrogenase levels (normal vs. abnormal), performance status (0-1 vs. 2) and institution.
Patients were asked to keep diaries and record whether during the past 3 weeks they had experienced symptoms in their hands and/or feet such as tingling/numbness, pain, redness, swelling, and desquamation, and if so, whether the symptoms interfered with daily activities.
After a median follow-up of 16.1 months, investigators assessed hand-foot syndrome rates by grade were as follows:
• Grade 1: 21% for the capecitabine arm vs. 28% for the S-1 arm (not significant).
• Grade 2: 30% vs. 14% (P = .02).
• Grade 3: 21% vs. 4% (P = .003).
The incidence of patient-assessed hand-foot syndrome of all grades was 84% in the capecitabine arm and 58% in the S-1 arm (P = .004). Patient-reported grade 3 hand-foot syndrome occurred in 18% vs. 5%, respectively (P = .05).
The only other toxicity occurring more frequently among patients on S-1 was anorexia, which occurred in 29% of patients on capecitabine compared with 41% with S-1. Grade 3 or greater anorexia occurred in 3% vs. 13%, respectively (P = .03).
Significantly more dose reductions were required for patients on capecitabine (69% vs. 41%, P = .0008). The median relative dose intensity was higher for patients on S-1 (89% vs. 95%, P = .035).
Among all patients, median progression-free survival was 8.18 months with capecitabine vs. 8.39 months with S-1, a difference that was not significant. There was a trend toward better progression-free survival for patients in each arm who received bevacizumab (8.74 vs. 6.37 months without bevacizumab), but this difference was also not significant.
Overall survival rates at 12 months were 67% with capecitabine and 62% with S-1 (not significantly different), and respective rates at 18 months were 50% vs. 39%. The hazard ratio for mortality with S-1 was 1.28 (not significant).
The study was sponsored by the Dutch Colorectal Cancer Group, with research funds supplied by Nordic Pharma BV. Dr. Kwakman disclosed receiving an honorarium from the company.
