Abstract P6-11-13: Phase I Study of Combined S-1 Plus Weekly Paclitaxel Therapy in Patients with Metastatic Breast Cancer

Abstract

Abstract Introduction: S-1, a novel anticancer compound, contains tegafur, a prodrug of fluorouracil (FU), 5-chloro-2.4-dihydroxypyridine, which prevents FU degradation, and potassium oxonate, which prevents drug-induced diarrhea, has a broad spectrum of activity against gastric, colorectal, head & neck, and breast cancers. While combined S-1 with cisplatin or paclitaxel (PAC) therapy is feasible and highly active against gastrointestinal cancer, the feasibility in breast cancer patients has not yet been clarified. We conducted a phase I study of combined S-1 plus weekly PAC therapy (S-1/PAC) to determine the maximum tolerated dose (MTD), recommended dose (RD) and dose-limiting toxicities (DLT) in patients (pts) with HER2-negative, taxane-naïve metastatic breast cancer (MBC). Methods: S-1 was administered orally from day 1 through day 14 and PAC was administered intravenously on days 1, 8 and 15 of each 28-day cycle. Since S-1 is prescribed at the dose of 80mg/m2 in monotherapy, the primary dose levels (level 1) were set at 65 and 70mg/m2, respectively. The final dose (level 3) was set at 80mg/m2 for each drugs. DLT was defined over 2 cycles. Results: Ten MBC pts were enrolled in the study. No DLTs were documented. Although grade 1 or 2 adverse events were seen in all pts, no cases of febrile neutropenia or Gr 4 neutropenia were observed. Of the 8 evaluable pts, 3 pts achieved partial response and 4 pts had stable disease. Conclusion: Based on the results of this study, RD was determined to be 80mg/m2 for either drugs. We conclude that S-1/PAC was well-tolerated and highly active against HER2-negative MBC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-11-13.