A randomized trial of capecitabine (C) given intermittently (IC) rather than continuously (CC) compared to classical CMF as first-line chemotherapy for advanced breast cancer (ABC)

Abstract

1031 Background: Intensive treatment is not indicated for many women having first line chemotherapy for ABC. We sought to determine for such women whether oral C was preferable to classical CMF, and whether C given continuously (CC) was preferable to the same total dose given intermittently for 14 of every 21 days (IC). Methods: 325 women were randomized between June 01 and July 05 to either IC (2,000mg/m2/d for 14 of every 21d), or CC (1,300mg/m2/d for 21 of every 21d), or CMF (cyclophosphamide 100mg/m2/d p.o. d1–14; methotrexate 40mg/m2 and 5-FU 600mg/m2, IV d1&8, every 28d). Treatment was continued until disease progression (PD), unacceptable toxicity, or intolerance. Clinical and quality of life (QOL) assessments were 3–4 wkly, and imaging was 3 monthly, both until PD. The primary endpoint was quality adjusted progression-free survival (QAPFS). Overall survival (OS), PFS, response rates (RR=CR+PR), QOL, acceptability of chemotherapy and adverse events (AE) were secondary endpoints. The analysis plan was to first compare IC v CC, and if p>0.05, then to combine the two arms (C = IC + CC) for comparisons v CMF. Primary analyses were with the logrank test. Cox’s models were used to calculate hazard ratios (HR), 95% confidence intervals (CI), and to adjust for other factors. All p-values and CI are 2-sided. Results: OS was longer with C than CMF (HR .72, CI .55 to .94, p=.02, medians 22 v 18 mo). PFS was similar for C and CMF overall (HR .86, CI .67 to 1.1, p=.2, median 7 mo), and over the first 6 mo (HR 1.15, CI .81 to 1.6), but longer on C than CMF beyond 6 mo (HR .62, CI .44 to .87). Response rates were similar on C and CMF (21% v 18%, p=.8). Febrile neutropenia, infection, and sore mouth were more common on CMF; hand-foot syndrome was more common on C. Chemotherapy was continued beyond 6 mo in 40% on C but only 21% on CMF. PFS, OS, RR and AE were similar for IC and CC (p>0.4). Cox’s models adjusting for baseline factors corroborated all results and conclusions. Analyses of QAPFS, QOL, and acceptability of chemotherapy will be available in June 07. Conclusion: C improved overall survival with less toxicity and greater tolerability than classical CMF. C is a good first line option when more intensive treatment is not indicated. [Table: see text]