Standard-dose vs fixed-dose capecitabine in patients with advanced gastrointestinal and metastatic breast cancer.

Abstract

1091 Background: Capecitabine at the FDA-approved standard dose (SD) of 1250 mg/m² twice daily for 14 days with a 7-day break, has significant toxicities. We conducted a randomized trial comparing SD and fixed dose (FD) Capecitabine 1500 mg twice daily, 7 days on, 7 days off in patients with metastatic breast cancer (MBC) and advanced gastrointestinal (GI) cancers. We previously reported that in MBC cohort progression-free survival and overall survival were similar, and FD had significantly lower toxicities. We now present time to treatment failure (TTF) and toxicity in MBC and GI cohorts. Methods: Patients with MBC or advanced GI cancers (colorectal, small bowel, gastroesophageal, pancreatic and bile duct) with any prior lines of therapy were randomized 1:1 to either FD-7/7 or SD-14/7. Post hoc analysis was performed to determine TTF, and landmark analysis was performed for Freedom from Treatment Failure (FFTF). Capecitabine-related toxicities [diarrhea, hand foot syndrome (HFS) and stomatitis] were solicited and graded at each visit. Results: 182 patients were enrolled (N=93 FD, N=89 SD) of which 153 had MBC and 29 had an advanced GI cancer. Median TTF was 4.92 months (3.02, 5.93) in FD arm, and 3.11 months (2.49, 3.90) in SD arm (log rank p=0.0111). Landmark analysis of FFTF is shown in Table 1. At 24 months, the FFTF in the FD arm was 15.6%, while in the SD arm it was 2.5% (p=0.0054). Grade 2 and higher toxicities were more common in SD compared to FD, including HFS, diarrhea, and stomatitis (Table 1) Conclusions: Fixed-dose capecitabine at 1500 mg twice daily for 7 days on and 7 days off demonstrates a longer time to treatment failure compared to the standard FDA-approved dosing in patients with MBC and advanced GI cancers and is associated with significantly lower toxicities. Clinical trial information: NCT02595320 . Landmark freedom from treatment failure at 12, 24 and 36 months; solicited adverse events. Time FD-7/7, N=93 SD-14/7, N=89 P-value Survival Probability Estimate 3-month 61.3% 51.4% 0.1917 6-month 39.6% 30.6% 0.2224 12-month 23.8% 14.1% 0.1188 24-month 15.6% 2.5% 0.0054 Adverse Event Number (proportion) Diarrhea         Any Grade         Grade 2-4         Grade ≥ 3      51 (54.8%) 8 (8.6%) 3 (3.2%) 59 (66.3%) 35 (39.3%) 20 (22.5%) 0.1142 <0.0001 <0.0001 HFS       Any Grade         Grade 2-4         Grade ≥ 3  46 (49.5%) 13 (14.0%) 1 (1.08%) 61 (68.5%) 40 (44.9%) 15 (16.9%) 0.0090 <0.0001 0.0002 Stomatitis         Any Grade         Grade 2-4         Grade ≥ 3  24 (25.8%) 2 (2.2%) 0 (0.0%) 48 (53.4%) 13 (14.6%) 6 (6.7%) 0.0001 0.0023 0.0125* *Fisher’s exact test.