Combination of docetaxel and TSU-68, an oral antiangiogenic agent, in patients with metastatic breast cancer previously treated with anthracycline: randomized phase II multicenter trial.

Abstract

The novel oral antiangiogenic agent TSU-68 was investigated in patients with

metastatic breast cancer. Patients with anthracycline-pretreated metastatic

breast cancer were randomly assigned to receive either TSU-68 400 mg twice daily

on days 1-21 plus docetaxel 60 mg/m(2) on day 1 every 3 weeks, or docetaxel 60

mg/m(2) on day 1 every 3 weeks. The primary endpoint was progression-free

survival. Between November 2006 and December 2007, 81 patients were included in

this study (41 for TSU-68 plus docetaxel and 40 for docetaxel alone). Median

progression-free survival was 6.8 months (95 % confidence interval [CI] =

5.4-12.5 months) in the TSU-68 plus docetaxel group and 8.1 months (95 % CI =

4.0-13.7 months) in the docetaxel-alone group (hazard ratio [HR] = 1.0; 95 % CI =

0.6-1.8; p = 0.95). There were no significant differences in the overall response

rates and overall survival between groups (p = 0.29 and p = 0.42, respectively).

In subgroup analysis, TSU-68 plus docetaxel was associated with better overall

survival than docetaxel alone in anthracycline-resistant patients (HR = 0.3; 95 %

CI = 0.1-0.8; p = 0.02). The most frequent adverse events were neutropenia and

anorexia in both arms. Although both regimens were well tolerated, grade 3/4

non-hematologic toxicity was more frequently observed in the TSU-68 plus

docetaxel group. Combination of TSU-68 and docetaxel is well tolerated but failed

to demonstrate superior efficacy over docetaxel alone in anthracycline-pretreated

breast cancer patients. As TSU-68 was associated with better survival in the

anthracycline-resistant subgroup, it should be further explored in this subgroup.