Safety and efficacy of S-1 monotherapy in elderly patients with advanced gastric cancer

Abstract

cancer is the most frequently encountered malignancy and the second leading cause of cancer-related death [3]. The prognosis of unresectable or recurrent tumors is very poor: the median survival time is about 4 months with best supportive care [4][5][6]. Although several randomized trials of treatments for advanced gastric cancer were conducted during the 1990s, with anthracyclines, mitomycin C, 5-fl uorouracil (5-FU), methotrexate, and cisplatin [7][8][9][10][11][12][13][14][15], no standard treatment for advanced gastric cancer was established.S-1 is an oral fl uoropyrimidine, consisting of tegafur (a prodrug of fl uorouracil), 5-chloro-2, 4-dihydropyrimidine (CDHP), and potassium oxonate. CDHP is an inhibitor of dihydropyrimidine dehydrogenase (DPD), which is the rate-limiting enzyme for the degradation of fl uorouracil [16]. Three randomized controlled trials of S-1 monotherapy have been reported from Japan. One was the Japan Clinical Oncology Group (JCOG) 9912 trial, which showed the noninferiority of S-1 to continuous infusion of 5-FU, adopted as the reference arm for patients with unresectable or recurrent gastric cancer, based on the result of the JCOG9205 trial [15,17]. The second trial was the S-1 plus cisplatin versus S-1 in RCT in the treatment for stomach cancer (SPIRITS) trial, conducted in 2007, which showed the superiority of S-1 plus cisplatin to S-1 alone in patients with advanced gastric cancer [18]. The third trial was the randomized phase III study of irinotecan plus S-1 (IRIS) versus S-1 alone as fi rst-line treatment for advanced gastric cancer (GC0301/TOP-002), which did not demonstrate the superiority of S-1 plus irinotecan (CPT-11) to S-1 alone [19]. From the results of these three phase III trials, S-1 plus cisplatin came to be recognized as the standard of care for patients with advanced gastric cancer in Japan, while S-1 monotherapy was a community standard until 2007.In recent years, the percentage of elderly people in the general population in Japan has increased remarkably, to more than 20%, owing to the prolonged lifespan of the Abstract Background. Although S-1 is effective against advanced gastric cancer (AGC), its effi cacy in elderly patients has not yet been investigated suffi ciently. We assessed the effi cacy and safety of S-1 monotherapy in elderly patients with AGC. Methods. We conducted a retrospective review of the data of 153 patients with unresectable/recurrent gastric adenocarcinoma who received S-1 monotherapy as fi rst-line chemotherapy at our institution. S-1 was administered orally twice daily at the dose of 40 mg/m 2 , on days 1-28, every 6 weeks. We categorized the patients into three groups, the young (≤65 years old), the middle-aged (66-75 years old), and the elderly (≥76 years old); and the drug toxicity, objective responses, progression-free survivals, and overall survivals were compared among the three groups. Results. The incidence of leukopenia of grade 3 or greater in the three groups was 7%, 5%, and 13%, and that of anemia was 9%, 18%, and 27%, respec...

Feasibility of adjuvant chemotherapy with S-1 consisting of a 4-week administration and a two-week rest period in patients with completely resected non-small cell lung cancer

“…The conventional schedule of S-1 administration was employed in the two studies. Since the present study comprised no patients with gastrectomy, we referred to the results reported by Tsushima et al (20). These results suggest that age is likely to affect RDI in the conventional S-1 schedule in NSCLC.…”

“…Aoyama et al (19) reported that in gastric cancer no difference was observed in the RDI of the adjuvant chemotherapy with S-1 in older (≥70 years old) and younger (<70 years old) patients with gastrectomy. However, Tsushima et al (20) demonstrated that median RDI in younger (≤65 years old) patients was likely to be lower compared to older (>65 years old) patients, including patients with unresectable gastric cancer. The conventional schedule of S-1 administration was employed in the two studies.…”

“…5 and 6). Tsushima et al (20) reported that CCr affected the dose intensity of S-1 in advanced gastric cancer (12). Several studies have demonstrated that approximately 50% of CDHP, a component of S-1 preventing degradation of 5-FU, was excreted in urine, and that renal function affects 5-FU concentrations in patients with solid tumors (21)(22)(23).…”

Prognostic Factors for Stage IV Gastric Cancer

“…25 Nevertheless, S-1 alone can be used safely for the elderly and poor PS patients, which most stage IV patients are. 26,27 Neoadjuvant chemotherapy settings have been discussed lately to give an adequate amount of antitumor agent and if possible, downstage the non-curative tumor to perform R0 operation. The European group has reported recently that R0 surgery increased but did not affect overall survival.…”

Safety and feasibility of S-1 adjuvant chemotherapy for gastric cancer in elderly patients

“…In their study of patients with advanced gastric cancer, Tsushima et al showed that S-1 monotherapy exhibited moderate efficacy in elderly patients (C76 years of age) and that these patients were at a higher risk of severe toxicities than the younger patients ( age B75 years). They recommended careful monitoring of toxicities in the elderly patients [6]. However, the safety and feasibility of adjuvant chemotherapy with S-1 in elderly patients has not been clarified.…”