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Updated: May 24, 2026
Spatial Measurements of Perfusion, Interstitial Fluid Pressure and Liposomes Accumulation in Solid Tumors
Published on: August 18, 2016
Effects of sorafenib on intra-tumoral interstitial fluid pressure and circulating biomarkers in patients with
Chandrajit P Raut1, Yves Boucher, Dan G Duda
1Department of Surgery, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, United States of America. craut@partners.org
Purpose:
Sorafenib is a multi-targeted tyrosine kinase inhibitor with therapeutic efficacy in several malignancies. Sorafenib may exert its anti-neoplastic effect in part by altering vascular permeability and reducing intra-tumoral interstitial hypertension. As correlative science with a phase II study in patients with advanced soft-tissue sarcomas (STS), we evaluated the impact of this agent on intra-tumor interstitial fluid pressure (IFP), serum circulating biomarkers, and vascular density.
Patients And Methods:
Patients with advanced STS with measurable disease and at least one superficial lesion amenable to biopsy received sorafenib 400 mg twice daily. Intratumoral IFP and plasma and circulating cell biomarkers were measured before and after 1-2 months of sorafenib administration. Results were analyzed in the context of the primary clinical endpoint of time-to-progression (TTP).
Results:
In 15 patients accrued, the median TTP was 45 days (range 14-228). Intra-tumoral IFP measurements obtained in 6 patients at baseline showed a direct correlation with tumor size. Two patients with stable disease at two months had post-sorafenib IFP evaluations and demonstrated a decline in IFP and vascular density. Sorafenib significantly increased plasma VEGF, PlGF, and SDF1α and decreased sVEGFR-2 levels. Increased plasma SDF1α and decreased sVEGFR-2 levels on day 28 correlated with disease progression.
Conclusions:
Pretreatment intra-tumoral IFP correlated with tumor size and decreased in two evaluable patients with SD on sorafenib. Sorafenib also induced changes in circulating biomarkers consistent with expected VEGF pathway blockade, despite the lack of more striking clinical activity in this small series.
Trial Registration:
ClinicalTrials.gov NCT00330421.
Insights
Sorafenib treatment in advanced soft-tissue sarcomas showed decreased tumor interstitial fluid pressure and altered biomarkers. However, these changes did not lead to significant clinical activity in this small patient group.
Area of Science:
- Oncology
- Pharmacology
- Biomarker Research
Background:
- Sorafenib is a multi-targeted tyrosine kinase inhibitor used in various cancers.
- Its anti-neoplastic effects may involve altering vascular permeability and reducing tumor interstitial hypertension.
- This study investigates sorafenib's impact on tumor interstitial fluid pressure (IFP) and biomarkers in advanced soft-tissue sarcomas (STS).
Purpose of the Study:
- To evaluate the effect of sorafenib on intra-tumor interstitial fluid pressure (IFP) in patients with advanced STS.
- To assess changes in serum circulating biomarkers and vascular density in response to sorafenib treatment.
- To correlate these findings with the clinical endpoint of time-to-progression (TTP).
Main Methods:
- A phase II study involving 15 patients with advanced STS receiving sorafenib 400 mg twice daily.
- Measurement of intratumoral IFP and plasma biomarkers before and after 1-2 months of sorafenib.
- Analysis of results in the context of TTP.
Main Results:
- Median TTP was 45 days. Baseline IFP correlated with tumor size.
- Two patients with stable disease showed decreased IFP and vascular density post-sorafenib.
- Sorafenib increased plasma VEGF, PlGF, and SDF1α, and decreased sVEGFR-2. Increased SDF1α and decreased sVEGFR-2 correlated with disease progression.
Conclusions:
- Pretreatment IFP correlated with tumor size and decreased in evaluable patients with stable disease on sorafenib.
- Sorafenib induced biomarker changes consistent with VEGF pathway blockade.
- Despite biomarker changes, striking clinical activity was not observed in this small cohort.
