S-1 may be alternative to fluorouracil for treatment of metastatic gastric cancer

S-1, a new oral fluoropyrimidine, was noninferior to fluorouracil and may potentially be used as first-line chemotherapy for metastatic gastric cancer.

Researchers conducted a phase-3 trial in 34 Japanese institutions on behalf of the gastrointestinal oncology study group of Japan Clinical Oncology Group. The goal of the study was to determine superiority of irinotecan plus ciplatin — a newer treatment regimen — to fluorouracil, and the noninferiority of S-1 to fluorouracil.

They randomly assigned patients aged 20 to 75 years to a continuous infusion of fluorouracil every four weeks (n=234), IV irinotecan and cisplatin every four weeks (n=236) or oral S-1 every six weeks (n=234).

At the primary analysis in March 2007, median OS was 10.8 months in the fluorouracil group, 12.3 months in the irinotecan plus cisplatin group and 11.4 months in the S-1 group. Treatment with irinotecan plus cisplatin was not superior to fluorouracil (HR=0.85; 95% CI, 0.70-1.04). Although S-1 was not superior to fluorouracil (P=.0336), noninferiority of S-1 to fluorouracil was confirmed by the researchers (HR=0.83; 95% CI, 0.68-1.01).

In November 2008, the additional analysis showed actual two-year survival was 14% among patients assigned to fluorouracil, 18% among those assigned to irinotecan plus cisplatin and 21% among those assigned to S-1. Again, irinotecan plus cisplatin was not superior to fluorouracil, and S-1 remained noninferior.

“In view of the effectiveness, safety, convenience and cost, continuous infusion of fluorouracil could be replaced by S-1 for first-line chemotherapy of metastatic gastric cancer,” the researchers said. – by Christen Haigh

Boku N. Lancet Oncol. 2009;doi:10.1016/S1470-2045(09)70259-1.

This large meta-analysis of over 5,000 patients with rectal cancer, obtained mostly from retrospective observational studies at tertiary cancer centers, evaluated the potential impact of more extended lymph node resection in rectal cancer compared with conventional surgery. There was no apparent survival difference or impact on either local or distant recurrence for an extended nodal resection vs. conventional surgery, but potentially greater long-term complications for extended nodal resection including greater urinary and sexual dysfunction. The study reinforces that the standard of care remains conventional surgery, usually a total mesorectal excision, for the resection of rectal cancer.

– David Ilson, MD

HemOnc Today Editorial Board member