Randomised phase II trial of S-1 plus oxaliplatin vs S-1 in patients with gemcitabine-refractory pancreatic cancer

S Ohkawa, T Okusaka, H Isayama, A Fukutomi, K Yamaguchi, M Ikeda, A Funakoshi, M Nagase, Y Hamamoto, S Nakamori, Y Tsuchiya, H Baba, H Ishii, Y Omuro, M Sho, S Matsumoto, N Yamada, H Yanagimoto, M Unno, Y Ichikawa, S Takahashi, G Watanabe, G Wakabayashi, N Egawa, M Tsuda, R Hosotani, C Hamada, I Hyodo, S Ohkawa, T Okusaka, H Isayama, A Fukutomi, K Yamaguchi, M Ikeda, A Funakoshi, M Nagase, Y Hamamoto, S Nakamori, Y Tsuchiya, H Baba, H Ishii, Y Omuro, M Sho, S Matsumoto, N Yamada, H Yanagimoto, M Unno, Y Ichikawa, S Takahashi, G Watanabe, G Wakabayashi, N Egawa, M Tsuda, R Hosotani, C Hamada, I Hyodo

Abstract

Background: This randomised, open-label, multicenter phase II study compared progression-free survival (PFS) of S-1 plus oxaliplatin (SOX) with that of S-1 alone in patients with gemcitabine-refractory pancreatic cancer.

Methods: Patients with confirmed progressive disease following the first-line treatment with a gemcitabine-based regimen were randomised to receive either S-1 (80/100/120 mg day(-1) based on body surface area (BSA), orally, days 1-28, every 6 weeks) or SOX (S-1 80/100/120 mg day(-1) based on BSA, orally, days 1-14, plus oxaliplatin 100 mg m(-2), intravenously, day 1, every 3 weeks). The primary end point was PFS.

Results: Between January 2009 and July 2010, 271 patients were randomly allocated to either S-1 (n=135) or SOX (n=136). Median PFS for S-1 and SOX were 2.8 and 3.0 months, respectively (hazard ratio (HR)=0.84; 95% confidence interval (CI), 0.65-1.08; stratified log-rank test P=0.18). Median overall survival (OS) was 6.9 vs 7.4 months (HR=1.03; 95% CI, 0.79-1.34; stratified log-rank test P=0.82). The response rate (RR) was 11.5% vs 20.9% (P=0.04). The major grade 3/4 toxicities (S-1 and SOX) were neutropenia (11.4% and 8.1%), thrombocytopenia (4.5% and 10.3%) and anorexia (12.9% and 14.7%).

Conclusions: Although SOX showed an advantage in RR, it provided no significant improvement in PFS or OS compared with S-1 alone.

Figures

Figure 1
Figure 1
CONSORT diagram.
Figure 2
Figure 2
Kaplan–Meier estimates of progression-free survival (PFS). The median PFS was 2.8 months (95% CI, 1.9–3.5) in the S-1 arm and 3.0 months (95% CI, 2.8–3.7) in the SOX arm.
Figure 3
Figure 3
Kaplan–Meier estimates of overall survival (OS). The median OS was 6.9 months (95% CI, 5.8–9.0) in the S-1 arm and 7.4 months (95% CI, 6.2–8.6) in the SOX arm.
Figure 4
Figure 4
Subgroup analyses of progression-free survival. *Some patients had overlapped locations.
Figure 5
Figure 5
Subgroup analyses of overall survival. *Some patients had overlapped locations.

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