Cancer Res Treat.  2016 Apr;48(2):499-507. 10.4143/crt.2015.089.

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

• Yoo C
• Kim SB
• Ro J
• Im SA
• Im YH
• Kim JH
• Ahn JH
• Jung KH
• Song HS
• Kang SY
• Park HS
• Chung HC

• KMID: 2454326
• DOI: http://doi.org/10.4143/crt.2015.089

Abstract

PURPOSE
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.
MATERIALS AND METHODS
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).
RESULTS
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.
CONCLUSION
Baseline PDGF-AA levels and dynamics of VEGF, PDGF-BB, CRP, and IL-6 levels were predictive for the efficacy of TSU-68.

Keyword

TSU-68; Breast neoplasms; Angiogenesis; Biological markers; Pharmacology

MeSH Terms

Arm
Biomarkers*
Breast Neoplasms*
Breast*
C-Reactive Protein
Disease-Free Survival
Enzyme-Linked Immunosorbent Assay
Fibroblast Growth Factors
Humans
Interleukin-6
Pharmacology
Plasma*
Platelet-Derived Growth Factor
Vascular Endothelial Growth Factor A
Biomarkers
C-Reactive Protein
Fibroblast Growth Factors
Interleukin-6
Platelet-Derived Growth Factor
Vascular Endothelial Growth Factor A

Figure

• 

  Fig. 1. Baseline levels of candidate plasma biomarkers between treatment arms. CRP, C-reactive protein; FGF, fibroblast growth factor; IL, interleukin; PDGF, platelet-derived growth factor; VEGF, vascular endothelial growth factor; DTX, docetaxel.

• 

  Fig. 2. Maximal fold changes in candidate plasma biomarkers during the entire study course between treatment arms. Ratio=(Geometric mean of maximal fold changes in the TSU-68 plus docetaxel group)/(Geometric mean of maximal fold changes in the docetaxel-alone group). CRP, C-reactive protein; FGF, fibroblast growth factor; IL, interleukin; PDGF, platelet-derived growth factor; VEGF, vascular endothelial growth factor; DTX, docetaxel.

• 

  Fig. 3. Progression-free survival according to the baseline plasma platelet-derived growth factor-AA (PDGF-AA) levels. DTX, docetaxel.

• 

  Fig. 4. (A-D) Association between progression-free survival and changes in plasma biomarkers from baseline to the end of the first cycle of the study treatment in the TSU-68 plus docetaxel group. CRP, C-reactive protein; IL, interleukin; PDGF, platelet-derived growth factor; VEGF, vascular endothelial growth factor.

Reference

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