Randomized trial of sequence vs. combination of capecitabine (X) and docetaxel (T): XT vs. T followed by X after progression as first-line therapy for patients (pts) with metastatic breast cancer (MBC)

Abstract

571 Background: Capecitabine (Xeloda [X]) and docetaxel (Taxotere [T]) are highly active single agents in MBC. The XT combination leads to superior overall survival (OS), time to progression (TTP) and response rate (RR) vs. T alone in anthracycline-preatreated MBC [O’Shaughnessy et al. J Clin Oncol 2002], although only one third of pts in the T group received X after progression. We designed this study to determine whether XT is better than sequential T→X in first-line MBC. Methods: 100 pts with measurable MBC, prior adjuvant anthracyclines (100%) but no prior chemotherapy for MBC and KPS ≥70 received 3-weekly cycles of either XT (X 1250mg/m2 bid d1–14 + T 75mg/m2 d1) or T→X (T 100mg/m2 d1 followed after progression by X 1250mg/m2 bid d1–14). X monotherapy data were not considered in the RR or TTP analyses but were included for OS and safety. Results: The XT and T→X arms were well balanced for prognostic factors: median age 48 (29–59) vs. 51 (31–64) years; median KPS 100 (70–100) in both arms; hormone-responsive disease 20 vs. 16%; dominant metastatic sites (liver 42 vs. 44%, lymph nodes 34 vs. 36%, lung 28 vs 24%, bone 20 vs 18%); number of involved organs (1 = 58 vs. 52%, >1 = 42 vs. 48%); median interval since prior adjuvant anthracyclines (18.5 vs. 17.0 months). Efficacy findings are shown in the table . 74% of the pts in the T→X arm crossed-over to X on progression. The post-study treatment rate was similar in both arms. The most common grade 3/4 adverse events (>5% of pts) with XT vs. T→X were: hand-foot syndrome 18 vs. 4%; stomatitis 16 vs. 8%; neutropenia 12 vs. 14%; neutropenic fever 12 vs. 14%; diarrhea 12 vs. 8%; fatigue 8 vs. 12%; alopecia 6 vs. 8%; edema 4 vs. 8%. Dose reductions were necessary for 52% of pts on XT and 36% of pts on T→X. Conclusions: XT provides significant RR, TTP and OS advantages over T→X. XT should be the standard therapy in fit poor-prognosis pts with aggressive disease. [Table: see text] No significant financial relationships to disclose.

A Three-Arm Randomized Phase II Study of Oral Vinorelbine Plus Capecitabine Versus Oral Vinorelbine and Capecitabine in Sequence Versus Docetaxel Plus Capecitabine in Patients with Metastatic Breast Cancer Previously Treated with Anthracyclines

“…Eight other small phase II or phase III studies comparing sequential versus combination approaches showed different results. Two (15,16) showed a better response rate in the combination arm, whereas others showed similar efficacy of both approaches (17)(18)(19)(20)(21)(22). Safety profile was better in the sequential arm in three of these eight trials (17)(18)(19), whereas two trials showed similar toxicity (15,20) and in three hematological toxicity was higher in the sequential arm (16,21,22).…”

Metastatic Breast Cancer: Focus on Capecitabine

“…To further study the question of combination versus sequential therapy, Beslija et al conducted a trial with 100 patients who had received prior adjuvant anthacyclines, but no prior chemotherapy for metastatic breast cancer. 27 Patients were randomized to capecitabine and docetaxel, at a reduced dose of docetaxel compared to the O'Shaughnessy trial, 13 or to full-dose docetaxel fol-lowed by capecitabine on progression. The response rates, time to progression and overall survival were superior in the combination arm, (RR 68 vs. 40%, P = 0.004; median TTP 9.3 vs. 7.7 months, P = 0.001; median OS 22 vs. 19 months, P = 0.006).…”

Achievements in Systemic Therapies in the Pregenomic Era in Metastatic Breast Cancer

“…In two other trials using a combination of capecitabine and taxanes with a similar design but differences in type of trial, doses and order of sequence of the two drugs, and taxane used [140,141], a higher ORR was reported, but this translated into a longer TTP and OS only in one trial [141]. Two phase II trials [142,143] and three phase II randomized trials [137][138][139] have compared combination chemotherapy with planned sequential therapy, with no significant differences in activity and efficacy but a better safety profile with sequential therapy in the majority of trials.…”