A randomized phase-II trial comparing sequential and concurrent paclitaxel with oral or parenteral fluorinated pyrimidines for advanced or metastatic gastric cancer

Abstract

Background The purpose of this study was twofold: (1) to compare S-1 with infusional 5-fluorouracil (FU) to determine which would be a better partner of paclitaxel (PTX), and (2) to compare a concurrent strategy with a sequential one, the latter strategy being the one that is widely used in Japanese general practice. Methods The 161 eligible patients were randomized into four arms to receive the following regimens: A (sequential), intravenous 5-FU at 800 mg/m 2 for 5 days every 4 weeks followed by weekly PTX at 80 mg/m 2 ; B (sequential), S-1 at 80 mg/m 2 for 4 weeks and 2-week rest followed by PTX; C (concurrent), intravenous 5-FU at 600 mg/m 2 for 5 days and weekly PTX at 80 mg/m 2 every 4 weeks; and D (concurrent), S-1 for 14 days and PTX at 50 mg/m 2 on days 1 and 8 every 3 weeks. The primary endpoint was the overall survival (OS) rate at 10 months. Results The ten-month OS rates in arms A, B, C, and D were 63, 65, 61, and 73%, respectively. The OS was best in the concurrent S-1/PTX arm, with a mean survival time of 123Gastric Cancer (2012) 15:363-369 DOI 10.1007 15.4 months, but no significant difference was observed between the four arms. Response rates were higher in the concurrent arms than in the sequential arms. Conclusion Our study did not show sufficient prolongation of survival with the concurrent strategy to proceed to a phase-III trial; however, the sequential arms showed survival comparable to that in the concurrent arms, with less toxicity. In patients who are ineligible for cisplatin (CDDP), sequential treatment starting with S-1 and proceeding to PTX would be a good alternative strategy, considering quality of life (QOL) and the cost-benefits of an oral agent as first-line treatment.

Neoadjuvant Chemotherapy Followed by Surgery versus Surgery Alone for Gastric Carcinoma: Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…Recently, the feasibility of SC was tested in an adjuvant setting to see whether this combination regimen is suitable for a test arm of a future Phase III trial which revealed that SC was not tolerable when it was started just after surgery, but was feasible and safe when provided preoperatively [53]–[57]. Paclitaxel is another key drug used for metastatic disease and has been tested in an adjuvant setting in a phase III trial [58], [59]. Moreover, paclitaxel plus DDP (PC) demonstrated a high response rate and feasibility for metastatic disease [58].…”

Can S-1 replace fluorouracil for advanced gastric cancer? A PRISMA-compliant systematic review and meta-analysis

“…Two studies compared S-1 alone with 5-FU alone (S-1 vs 5-FU), [14,17] 3 compared S-1 plus cisplatin with 5-FU plus cisplatin (SP vs FP), [13,15,16] and 2 compared S-1 plus paclitaxel with 5-FU plus paclitaxel (SPtx vs FPtx). [11,12] Regimens were similar with respect to doses and schedules in every trial. There were no significant differences in the baselines between S-1-containing and 5-FU-containing groups in these studies as reported.…”

“…[17] The main characteristics of the included trials were shown in Table 1. Six studies were performed in East Asia (3 in Japan [12,14,17] and 3 in China [11,15,16] ), and the remaining study was a non-Asian global phase III trial performed in 24 countries. [13] All studies were multicenter in nature, involving 8 to 146 centers.…”

“…Median OS ranged from 8.3 to 15.2 months in the S-1-containing groups and 7.9 to 14.2 months in the 5-FU-containing groups (Table 2). [12–17] Two studies reported that S-1-containing regimens were superior to 5-FU-containing regimens, [14,16] whereas the others reported that S-1-containing regimens were comparable or noninferior to 5-FU-containing regimens. The meta-analysis showed no statistically significant improvement of OS with S-1-containing regimens versus 5-FU-containing regimens (HR = 0.91, 95% confidence interval [CI] [0.83–1.01], P = 0.07; P of heterogeneity = 0.18, I 2 = 34%; Fig.…”

“…[11–14,16,17] One study reported that no difference in TTF was observed between S-1-containing and 5-FU-containing regimens but did not provide exact data for meta-analysis. [12] Another study reported the Kaplan-Meier curve and HR of TTF; however, the median of TTF obtained through correspondence with the original investigators was only 16 days and 20 days which were observed in 17 patients and 19 patients of the S-1-containing and 5-FU-containing groups, respectively. [11] Consequently, these 2 studies were excluded from the meta-analysis.…”