Cytokine and angiogenic factors associated with efficacy and toxicity of pazopanib in advanced soft-tissue sarcoma: an EORTC-STBSG study
Background:Pazopanib has activity in relapsed non-adipocytic soft-tissue sarcomas (STS). A series of serum cytokines and angiogenic factors (CAFs) at baseline and changes in soluble vascular endothelial growth factor receptor-2 (sVEGFR2) or placental-derived growth factor (PlGF) levels during treatm...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
17 July 2012
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| In: |
British journal of cancer
Year: 2012, Volume: 107, Issue: 4, Pages: 639-645 |
| ISSN: | 1532-1827 |
| DOI: | 10.1038/bjc.2012.328 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1038/bjc.2012.328 Verlag, Volltext: https://www.nature.com/articles/bjc2012328 
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| Author Notes: | S. Sleijfer, T. Gorlia, C. Lamers, H. Burger, J.-Y. Blay, A. Le Cesne, M. Scurr, F. Collin, L. Pandite, S. Marreaud, P. Hohenberger |
| Summary: | Background:Pazopanib has activity in relapsed non-adipocytic soft-tissue sarcomas (STS). A series of serum cytokines and angiogenic factors (CAFs) at baseline and changes in soluble vascular endothelial growth factor receptor-2 (sVEGFR2) or placental-derived growth factor (PlGF) levels during treatment were explored for their association with outcome.Methods:Twenty-three baseline CAFs, and sVEGFR2 and PlGF changes were measured in 85 and 32 patients, respectively. Associations between baseline CAF levels and efficacy parameters, plus between-week 12 sVEGFR2 and PlGF levels and pazopanib-specific toxicities were investigated.Results:At baseline, low interleukin (IL)-12 p40 subunit and MPC3 levels were associated with better progression-free survival (PFS) at 12 weeks (PFS12wks), low basic nerve growth factor and hepatocyte growth factor with a better PFS, and low inter-cellular adhesion molecule-1 and IL-2 receptor alpha with prolonged overall survival (OS; all P<0.05). Pazopanib decreased sVEGFR2 and increased PlGF levels. Low sVEGFR2 and high PlGF levels at week 12 were associated with higher-grade hypertension, with TSH elevations and with poorer PFS12wks, and OS (both P<0.05).Conclusion:Several baseline CAFs were related to outcome parameters. Low sVEGFR2 and high PlGF at week 12 associate with several pazopanib-specific toxicities and poorer efficacy. If confirmed, these factors may be used as early markers for response to and toxicity from pazopanib, enabling further individualisation of STS treatment. |
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| Item Description: | Gesehen am 18.10.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1532-1827 |
| DOI: | 10.1038/bjc.2012.328 |