Cytokine and angiogenic factors associated with efficacy and toxicity of pazopanib in advanced soft-tissue sarcoma: an EORTC-STBSG study.
Br J Cancer
; 107(4): 639-45, 2012 Aug 07.
Article
in En
| MEDLINE
| ID: mdl-22805326
ABSTRACT
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 (PFS(12wks)), 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 PFS(12wks), 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pregnancy Proteins
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Pyrimidines
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Sarcoma
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Sulfonamides
/
Cytokines
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Angiogenesis Inhibitors
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Vascular Endothelial Growth Factor Receptor-2
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Membrane Proteins
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Antineoplastic Agents
Type of study:
Risk_factors_studies
Limits:
Adolescent
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Adult
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Aged
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Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Br J Cancer
Year:
2012
Type:
Article
Affiliation country:
Netherlands