Capecitabine (X) and taxanes in patients (pts) with anthracycline-pretreated metastatic breast cancer (MBC): Sequential vs. combined therapy results from a MOSG randomized phase III trial

Abstract

570 Introduction: Capecitabine (Xeloda [X]) shows synergy with taxanes and adding X to docetaxel (T) extends overall survival (OS), response rate (RR) and progression free-survival (PFS) beyond T alone. Sequential single-agent therapy could confer convenience benefits and may be more appropriate than combination chemotherapy for some pts. Methods: Pts with anthracycline-pretreated MBC received 3-weekly cycles of 1 of the following regimens: X→taxane (X 1250mg/m2 bid d1–14, followed after progression (PD) by T 100mg/m2 or paclitaxel [P] 175mg/m2 day 1; X+P (X 825mg/m2 bid days 1–14 + P 175mg/m2 day 1) or X+T (X 825mg/m2 bid days 1–14 + T 75mg/m2 day 1). Results: Of the 368 pts enrolled, 91 are either still on therapy or not evaluable. The table shows baseline characteristics, efficacy and safety in evaluable pts. Median follow up is 15.5 months. Median doses for X in each arm (1st cycle vs. 8th cycle, mg/m2 bid): 1218 vs. 1054; 948 vs. 900; 846 vs. 751. Median doses for P and T (1st cycle vs. 8th cycle, mg/m2): 173 vs. 169 and 75 vs. 72, respectively. In the X→taxane arm, 58 pts (64%) received sequential taxane; the remainder did not receive a taxane, either because they were still on X, had CR or had rapid PD. Conclusions: RR is higher with XP and XT, but PFS and OS are similar at a median follow-up of 15.5 months. All regimens were well tolerated with minimal grade 4 AEs. Because there is no clear superiority of sequential vs. combined therapy, pt characteristics are likely to be used to decide which regimen is the most appropriate. [Table: see text] [Table: see text]

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).…”

Phase 2 trial of a novel capecitabine dosing schedule in combination with bevacizumab for patients with metastatic breast cancer

“…[16][17][18] Prospective randomized studies often have explored reduced-dose capecitabine in doublets with other cytotoxic agents, making these data difficult to interpret for the impact of the modified capecitabine dose alone. 19,[26][27][28] An additional complication arises from data indicating that body surface area-based dosing may not be ideal. 29 We developed a method to predict the optimal dosing of chemotherapy and applied it specifically to capecitabine.…”

“…12,14 Several studies have explored alternative capecitabine doses and schedules as monotherapy and in capecitabine-based combinations for both breast and colorectal cancers. [16][17][18][19][20] However, these dose modifications were derived empirically with unclear impact on patient outcome.…”

Survival Data of Patients with Anthracycline‐ or Taxane Pretreated or Resistant Metastatic Breast Cancer

“…resulted in higher response rates and time to progression, they have not improved overall survival or quality of life. 5,6 In addition, the absence of planned crossover in most studies meant that not all patients in the sequential groups received the second agent, a situation that 25 21-day cycle (n=230) HR = hazard ratio; CI = confidence interval; PFS = progression-free survival; TTP = time to progression; HER2 = human epidermal growth factor receptor-2. a Primary end point.…”