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.
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.
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Sung-Bae
SB
Kim
Changhoon
C
Yoo
Jungsil
J
Ro
Seock-Ah
SA
Im
Young-Hyuck
YH
Im
Jee Hyun
JH
Kim
Jin-Hee
JH
Ahn
Kyung Hae
KH
Jung
Hong Suk
HS
Song
Seok Yun
SY
Kang
Hee Sook
HS
Park
Hyun-Cheol
HC
Chung
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D018943:Anthracyclines / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D000078183:Oxindoles; D011422:Propionates / Q000008:administration & dosage / Q000009:adverse effects; D011758:Pyrroles; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
D020533:Angiogenesis Inhibitors; D018943:Anthracyclines; D000970:Antineoplastic Agents; D007211:Indoles; D000078183:Oxindoles; D011422:Propionates; D011758:Pyrroles; D043823:Taxoids; D000077143:Docetaxel; C412603:orantinib