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

T Ioka, Y Komatsu, N Mizuno, A Tsuji, S Ohkawa, M Tanaka, H Iguchi, A Ishiguro, M Kitano, T Satoh, T Yamaguchi, K Takeda, M Kida, K Eguchi, T Ito, M Munakata, T Itoi, J Furuse, C Hamada, Y Sakata, T Ioka, Y Komatsu, N Mizuno, A Tsuji, S Ohkawa, M Tanaka, H Iguchi, A Ishiguro, M Kitano, T Satoh, T Yamaguchi, K Takeda, M Kida, K Eguchi, T Ito, M Munakata, T Itoi, J Furuse, C Hamada, Y Sakata

Abstract

Background: We aimed to compare the efficacy and safety of irinotecan/S-1 (IRIS) therapy with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer.

Methods: Patients were treated with oral S-1 (80-120 mg for 14 days every 4 weeks) plus intravenous irinotecan (100 mg m-2 on days 1 and 15 every 4 weeks; IRIS group) or oral S-1 group (80-120 mg daily for 28 days every 6 weeks). The primary endpoint was progression-free survival (PFS).

Results: Of 137 patients enrolled, 127 were eligible for efficacy. The median PFS in the IRIS group and S-1 monotherapy group were 3.5 and 1.9 months, respectively (hazard ratio (HR)=0.77; 95% confidence interval (CI), 0.53-1.11; P=0.18), while the median overall survival (OS) were 6.8 and 5.8 months, respectively (HR=0.75; 95% CI, 0.51-1.09; P=0.13). Response rate was significantly higher in the IRIS group than in the S-1 monotherapy group (18.3% vs 6.0%, P=0.03). Grade 3 or higher neutropenia and anorexia occurred more frequently in the IRIS group.

Conclusions: There was a trend for better PFS and OS in the IRIS group that could be a treatment arm in the clinical trials for gemcitabine-refractory pancreatic cancer.

Conflict of interest statement

Tatsuya Ioka has received research fund and honoraria including Speakers from Bureau from Taiho Pharmaceutical and Yakult Honsha. Tatsuya Ioka held an advisory role for Taiho Pharmace utical. Yoshito Komatsu has received research fund and honoraria from Yakult Honsha and Taiho Pharmaceutical. Nobumasa Mizuno, Haruo Iguchi, and Junji Furuse have received honoraria from Taiho Pharmaceutical and Yakult Honsha. Nobumasa Mizuno and Atsushi Ishiguro have received research fund from Taiho Pharmaceutical. Akihito Tsuji and Junji Furuse have received research fund from Taiho Pharmaceutical and Yakult Honsha. Taroh Satoh has received research fund from Yakult Honsha. Junji Furuse and Yuh Sakata held an advisory role for Taiho Pharmaceutical and Yakult Honsha. Chikuma Hamada held an advisory role for Yakult Honsha. All the remaining authors have declared no conflict of interest.

Figures

Figure 1
Figure 1
Trial profile. *Represents that patients can be included in more than one category.
Figure 2
Figure 2
Kaplan–Meier curves for progression-free survival assessed by RECIST (A) and overall survival (B). CI, confidence interval; HR, hazard ratio; IRIS, irinotecan plus S-1; OS=overall survival; PFS=progression-free survival.
Figure 3
Figure 3
Subgroup analyses of progression-free survival assessed by RECIST (A) and overall survival (B). CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; IRIS, irinotecan plus S-1.

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