Late phase II study of S-1 in patients with taxane resistant breast cancer

Abstract

745 Background: S-1 is a novel oral anticancer agent, contains tegafur (FT: prodrug of 5-fluorouracil), 5-chloro-2,4-dihydroxypyridine (CDHP: dehydropyrimidine dehydrogenase inhibitor), and potassium oxonate (Oxo: orotate phosphoribosyl transferase inhibitor) at a molar ratio of FT:CDHP:Oxo = 1:0.4:1. We conducted this study to evaluate the efficacy and safety of S-1, in patients (pts) with taxane resistant breast cancer (BC). Methods: Eligibility criteria were as follows: informed consent was obtained, age >=20 to <75, had histologicaly confirmed BC, had metastatic BC, had received one or two prior chemotherapeutic regimens one of which had to have contained paclitaxel or docetaxel, progression or relapse was confirmed within 6 months after taxane treatment, has one or more measurable region, has adequate organ function, PS 0–2, life expectancy more then 3 months. S-1 was given orally at 40mg/m2 b.i.d. for 28 consecutive days followed by 14 days rest period and repeated in 42 day cycles. The cycles were continued until disease progressed. Results: Between November 2001 and April 2003, 56 pts were registered on the trial, and 55 pts received treatment with S-1. All pts had received taxane treatment, and 40 (72.7%) of 55 pts had received anthracycline containing chemotherapy. Response was evaluated based on RECIST criteria at independent review committee. Twelve (21.8%) of the 55 pts (95% CI 11.8 – 35.0%) were confirmed partial responders and there was no complete responder. The median overall survival period was 470 days (Follow-up is being continued). The grade (G) 4 treatment-related adverse event (AE) wasn't observed. The most common G3 treatment-related AEs were neutoropenia (10.9%), leucopenia (9.1%), diarrhea (5.5%) and anorexia (5.5%). There was no G3–4 hand-foot syndrome, even G2 was 5.5%. Almost all AEs were manageable with brief drug interruption or dose reduction. Conclusions: S-1 is an active drug in the treatment of taxane resistant BC and has favorable toxicity profiles. No significant financial relationships to disclose.