Adjuvant chemotherapy of S-1 versus S-1 plus metformin for resected pancreatic cancer: A multicenter and randomized phase II trial

Autor: Noboru Yahara, Hiroshi Nakano, Mototsugu Shimokawa, Yutaka Itoh, Takeshi Sudo, Kouji Oota, Takuji Naka, Toshifumi Matsumoto, Hideki Aoki, Ichiro Sakamoto, Masato Narita, Masayuki Furukawa, Terumasa Hisano
Rok vydání: 2019
Předmět:
Zdroj: Journal of Clinical Oncology. 37:TPS474-TPS474
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2019.37.4_suppl.tps474
Popis: TPS474 Background: Adjuvant chemotherapy with S-1 in patients with resected pancreatic ductal adenocarcinoma (PDAC) improved the 5-year survival rate to 44.1% and therefore has been a standard of care in Japan. Recent epidemiologic data has revealed possibility of metformin (a drug for type II diabetes) improving the prognosis of PDAC. In this context, we compare the efficacy and safety of S-1 plus metformin with S-1 alone as adjuvant chemotherapy in patients with resected PDAC. Methods: This multicenter-randomized-phase II study is conducted at 29 institutions in Japan (Registry Number; UMIN000020681). Key eligibility criteria are age 20 years or more with good performance status; histologically proven PDAC of stage I-II without macroscopic residual tumor. Patients receiving preoperative treatment for PDAC and previously treated with DPP-4 inhibitor, GLP-1, and metformin are excluded. After giving written consent to the study, patients are randomly assigned either study group (S-1 plus metformin) or control group (S-1 alone), balancing residual tumor status, nodal status, and institutions. S-1 is given orally for 2 weeks in a 3-week cycle. Cycles are lasted for 6 months. In the study group, metformin is administrated together with S-1 for 2 years. The treatment would be discontinued when the patient has either recurrence or unacceptable toxicity. The primary endpoint is 2-year OS, and the secondary endpoints are relapse-free survival and incidence rate of adverse events. Sample size was calculated based on the data in previous trials, with an expected 2-year survival rate in the control group of 65%. An improvement in 2-year-survival rate from 65% in the control group to 78% in the study group, yielding a hazard ratio of 0.58, is considered clinically relevant in this population. A total of 73 events in each group were required for a power of 80% at a two-sided alpha 20% to detect a difference in OS using an unstratified log-rank test. A total of 160 patients (80 per group) were estimated to achieve the specified number of events in the scheduled follow-up. Duration of this study would be 5 years and it has been started from January 2018. Until September 2018, 17 patients have been enrolled. Clinical trial information: UMIN000020681.
Databáze: OpenAIRE
Externí odkaz: