Circulating Plasma Biomarkers for TSU-68, an Oral Antiangiogenic Agent, in Patients with Metastatic Breast Cancer

• Published in: Cancer research and treatment Vol. 48; no. 2; pp. 499 - 507
• Main Authors: Yoo, Changhoon, Kim, Sung-Bae, Ro, Jungsil, Im, Seock-Ah, Im, Young-Hyuck, Kim, Jee Hyun, Ahn, Jin-Hee, Jung, Kyung Hae, Song, Hong Suk, Kang, Seok Yun, Park, Hee Sook, Chung, Hyun-Cheol
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Cancer Association 01-04-2016; 대한암학회
• Subjects: Adult; Aged; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - therapeutic use; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor - blood; Breast Neoplasms - blood; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; C-Reactive Protein - analysis; Enzyme-Linked Immunosorbent Assay; Female; Fibroblast Growth Factors - blood; Humans; Indoles - administration & dosage; Indoles - pharmacology; Indoles - therapeutic use; Interleukin-6 - blood; Middle Aged; Neoplasm Metastasis - drug therapy; Original; Propionates - administration & dosage; Propionates - pharmacology; Propionates - therapeutic use; Taxoids - administration & dosage; Taxoids - pharmacology; Taxoids - therapeutic use; Vascular Endothelial Growth Factor A - blood; 의약학; Angiogenesis; TSU-68; Breast neoplasms; Pharmacology; Biological markers
• ISSN: 1598-2998; 2005-9256
• DOI: 10.4143/crt.2015.089

This study analyzed the role of plasma biomarkers for TSU-68 in a previous phase II trial comparing TSU-68 plus docetaxel and docetaxel alone in patients with metastatic breast cancer.
A total of 77 patients were eligible for this study (38 in the TSU-68 plus docetaxel arm and 39 in the docetaxel alone arm). Blood samples were collected prior to the start of each cycle, and vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)-AA, -AB, -BB, fibroblast growth factor, M30, C-reactive protein (CRP), and interleukin 6 (IL-6) levels were measured using enzyme linked immunosorbent assay. The primary endpoint was progression-free survival (PFS).
In patients with baseline PDGF-AA ≥ median, median PFS was significantly worse in the TSU-68 plus docetaxel group than in the docetaxel alone group (5.4 months vs. 13.7 months, p=0.049), while a trend toward a PFS benefit was observed in those with baseline PDGF-AA < median (9.7 months vs. 4.0 months, p=0.18; p for interaction=0.03). In the TSU-68 plus docetaxel group, PFS showed significant association with fold changes in CRP (p=0.001), IL-6 (p < .001), PDGF-BB (p=0.02), and VEGF (p=0.047) following the first treatment cycle.
Baseline PDGF-AA levels and dynamics of VEGF, PDGF-BB, CRP, and IL-6 levels were predictive for the efficacy of TSU-68.