Researchers from Japan have reported that an oral fluoropyrimidine, S-1, improves survival by 10% in patients with resected stage II-III gastric cancer. The details of this study were published in the November 1, 2007 issue of the New England Journal of Medicine.1
There have been several randomized trials to determine the efficacy of adjuvant therapy in the treatment of resected gastric cancer. A review article in the September 1, 2005, issue of the Journal of Clinical Oncology evaluated all the relevant studies to date.2 These reviewers stated that the results of a large North American Study (Gastrointestinal Cancer Intergroup Trial INT 0116) showing that postoperative chemoradiotherapy conferred a survival advantage compared to surgery alone has led to a new standard of care in the United States. After a thorough review of this subject the authors concluded that more studies were needed to optimize therapy and to move to a better consensus and standardization of care. Since this time there have been both positive and negative studies concerning adjuvant therapies for resected gastric cancer. Most of the positive studies come from Asia, especially Japan, where the incidence of gastric cancer is high. These studies have suggested that adjuvant chemotherapy without radiation therapy is effective.
S-1 is described as “an orally active combination of tegafur (a prodrug that is converted by cells to fluorouracil), gimeracil (an inhibitor of dihydropyrimidine dehydrogenase, which degrades fluorouracil), and oteracil (which inhibits the phosphorylation of fluorouracil in the gastrointestinal tract, thereby reducing the gastrointestinal toxic effects of fluorouracil) in a molar ratio of 1:0.4:1.” S-1 has been studied in patients with advanced gastric cancer with a relatively high response rate.3 Long-term survival of selected patients with metastatic gastric cancer treated with S-1 has also been reported.4 Prior to the present study it was determined that gastrectomy did not affect the pharmacokinetics of S-1.5
Researchers involved in this study randomly allocated 529 patients with stage II-III gastric cancer to receive post-operative S-1 or placebo. All patients had gastrectomy and extended lymph node dissection. This trial was stopped early by the data and safety monitoring committee at the first interim analysis. The three year overall survival of the S-1 group was 80% compared to 70% in the surgery only group. This represented a 32% reduction in the death rate. Side effects of S-1 included anorexia, nausea and diarrhea.
Comments: This is convincing data that adjuvant chemotherapy following gastrectomy and extensive lymph node dissection improves survival. In addition, oral S-1 appears to be a very active combination of oral drugs for treating gastric cancer.
Related News:
Pre- and Post-Operative Chemotherapy Improves Overall Survival in Gastroesophageal Cancer (7/7/2006)
Extensive Node Dissection by Experienced Surgeons Improves Survival from Gastric Cancer (3/28/2006)
Adjuvant Chemotherapy Does Not Affect Survival After Surgery for Gastric Cancer (9/7/2005)
Pre- and Post-Operative Chemotherapy Improves Survival in Gastroesophageal Cancer (5/17/2005)
Reference:
1 Sakuramoto S, Sasako M, Yamaguchi T, et al. Adjuvant chemotherapy for gastric cancer with S-1, and oral fluoropyrimidine. The New England Journal of Medicine 2007;357:1810-1820.
2 Lim L, Michael M, Mann GB, et al. Review Article: Adjuvant therapy in gastric cancer. Journal of Clinical Oncology. 2005;23:6220-6232.
3 Jeuna HC, Pha SY, Kim HK, et al. Multi-institutional phase II study of S-1 monotherapy in advanced gastric cancer with pharmacokinetic and pharmacogenomic evaluations. Oncologist 2007;12:543-554.
4 Hosokawa A, Sugiyama T, Ohtsu A, et al. Long-term outcomes of patients with metastatic gastric cancer after initial S-1 monotherapy. Journal of Gastroenterology 2007;42:533-538.
5 Kochi M, Fujii M, Kaiga T, et al. Effect of gastrectomy on the pharmacokinetics of S-1, an oral fluoropyrimidine, in resectable gastric cancer patients. Cancer Chemotherapy Pharmacology 2007;60:693-701.
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