Abstract OT2-2-07: A phase II study of S-1 (14 days' administration followed by 7 days' rest) for metastatic breast cancer
Authors: Hirano Akira , Hattori Akinori , Ogura Kaoru , Inoue Hiroaki , Okubo Fumie , Kamimura Mari , Sakaguchi Shiho , Kinoshita Jun , Miyamoto Reiko , Jibiki Norie , Naritaka Yoshihiko , Shimizu Tadao 
Published: May 2015

Abstract
Background
S-1, an orally administered fluorinated pyrimidine (FP), improves overall survival in the adjuvant setting of gastric and pancreatic cancer. It is also effective for metastatic breast cancer (Yamamoto et al. Anticancer Res 30:3827-32, 2010). Although S-1 is usually administered for 28 days followed by 14 days’ rest, severe adverse events are often observed by Day 15.
By altering the schedule into 14 days’ administration followed by 7 days’ rest, discontinuation of treatment can often be avoided in daily practice. This schedule maintains the same dose intensity.
Equally, an anti-tumor effect and fewer adverse events are observed in 14 days’ administration followed by 7 days’ rest than in 28 days’ administration followed by 14 days’ rest for the treatment of squamous cell carcinoma of the head and neck (Tsukuda et al. Br J Cancer 93:884-889, 2005).
In order to reduce the occurrence and severity of adverse events of S-1, we paid attention to dose reduction according to the renal function of patients. S-1 is comprised of tegafur, 5-chloro-2, 4-dihydroxy-pyridine(CDHP) and potassium oxonate. CDHP enhances the serum concentration of 5-FU by inhibiting dihydropyrimidine dehydrogenase (DPD), and it is excreted by the kidneys. Therefore, an accumulation of DPD in patients with renal dysfunction escalates the serum concentration of 5-FU and induces more severe adverse events. Thus, the dosage of S-1 should be reduced according to renal function.
Trial design
This is a phase II trial to evaluate the efficacy and toxicity of S-1 (14 days’ administration followed by 7 days’ rest) for metastatic breast cancer. S-1 is administered orally twice daily at a dose of 40-60 mg depending on the BSA and creatinine-clearance from Days 1 to 14, which is followed by 7 days’ rest. This treatment is repeated until disease progression.
(Trial registration :UMIN 000014096)
Eligibility criteria
Patients with histologically confirmed breast cancer, and recurrent and /or metastatic disease are included. Patients with HER2-positive (IHC:3+ or FISH+) tumor are excluded. Patients within 2 lines of previous chemotherapy for metastatic disease are allowed. Eligible patients are aged between 20 years and 80 years with a performance status of 0 to 2 and adequate organ function.
Specific aims
The primary endpoint is the response rate, and the secondary endpoints are disease control rate, progression-free survival, time to failure, toxicities and feasibility.
Statistical methods
The sample size was calculated using the Simon method, with a type I error of 5% and a study power of 90%. The unpromising response rate was 15% and the promising rate was 42%. The required number of patients was estimated to be 23.
Target accrual
Accrual of 25 patients was planned to produce a minimum of 23 evaluable patients. Patient accrual started in June 2014.
Citation Format: Akira Hirano, Akinori Hattori, Kaoru Ogura, Hiroaki Inoue, Fumie Okubo, Mari Kamimura, Shiho Sakaguchi, Jun Kinoshita, Reiko Miyamoto, Norie Jibiki, Yoshihiko Naritaka, Tadao Shimizu. A phase II study of S-1 (14 days' administration followed by 7 days' rest) for metastatic breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT2-2-07.