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Erschienen in: Targeted Oncology 3/2014

01.09.2014 | Original Research

Low level of baseline circulating VEGF-A is associated with better outcome in patients with vascular sarcomas receiving sorafenib: an ancillary study from a phase II trial

verfasst von: Nicolas Penel, Isabelle Ray-Coquard, Christine Bal-Mahieu, Christine Chevreau, Axel Le Cesne, Antoine Italiano, Emmanuelle Bompas, Stéphanie Clisant, Brigitte Baldeyrou, Amélie Lansiaux, Yves-Marie Robin, Jacques-Olivier Bay, Sophie Piperno-Neumann, Jean-Yves Blay, Charles Fournier

Erschienen in: Targeted Oncology | Ausgabe 3/2014

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Abstract

We have carried out a stratified phase II study of sorafenib (So) in patients with advanced angiosarcoma (n = 32) and epithelioid hemangioendothelioma (n = 13). This report concerns the correlative analysis of the predictive values of circulating pro/anti-angiogenetic biomarkers. Using the ELISA method (R&D Systems), circulating biomarkers (VEGF-A, in picograms per milliliter), thrombospondin-1 (TSP1, in micrograms per milliliter), stem cell factor (SCF, in picograms per milliliter), placental growth factor (PlGF, in picograms per milliliter), VEGF-C (in picograms per milliliter), and E-selectin (in nanograms per milliliter) were measured before So treatment and after 7 days. VEGF-A (mean value 475 vs. 541, p = 0.002), TSP1 (16 vs. 24, p = 0.0002), and PlGF (20.9 vs. 40.7, p = 0.0001) significantly increased during the treatment. Treatment did not affect the levels of SCF, VEGF-C, and E-selectin. Only two biomarkers were associated with better outcome as follows: VEGF-A and PlGF. Best objective response and non-progression at 180 days were associated with low level of VEGF-A at baseline (p = 0.04 and 0.03, respectively). There was a correlation between the circulating level of VEGF-A and time to progression (TTP) (r = −0.47, p = 0.001). Best objective response and non-progression at 180 days were not associated with baseline level of PIGF, but there was a correlation between the circulating level of PIGF at baseline and TTP. Low level of VEGF-A at baseline (<500) was significantly associated with better outcome.
Literatur
1.
Zurück zum Zitat Penel N, Marreaud S, Robin YM, Hohenberger P (2011) Angiosarcoma: state of the art and perspectives. Crit Rev Oncol Hematol 80:257–263PubMedCrossRef Penel N, Marreaud S, Robin YM, Hohenberger P (2011) Angiosarcoma: state of the art and perspectives. Crit Rev Oncol Hematol 80:257–263PubMedCrossRef
2.
Zurück zum Zitat Penel N, Bui BN, Bay JO, Cupissol D, Ray-Coquard I, Piperno-Neumann S, Kerbrat P, Fournier C, Taieb S, Jimenez M, Isambert N, Peyrade F, Chevreau C, Bompas E, Brain EG, Blay JY (2008) Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX study. J Clin Oncol 26:5269–5274PubMedCrossRef Penel N, Bui BN, Bay JO, Cupissol D, Ray-Coquard I, Piperno-Neumann S, Kerbrat P, Fournier C, Taieb S, Jimenez M, Isambert N, Peyrade F, Chevreau C, Bompas E, Brain EG, Blay JY (2008) Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX study. J Clin Oncol 26:5269–5274PubMedCrossRef
3.
Zurück zum Zitat Mehrabi A, Kashfi A, Fonouni H, Schemmer P, Hallscheidt P, Schirmacher P, Weitz J, Friess H, Buchler MW, Schmidt J (2006) Primary malignant hepatic epithelioid hemangioendothelioma. Cancer 107:2108–2121PubMedCrossRef Mehrabi A, Kashfi A, Fonouni H, Schemmer P, Hallscheidt P, Schirmacher P, Weitz J, Friess H, Buchler MW, Schmidt J (2006) Primary malignant hepatic epithelioid hemangioendothelioma. Cancer 107:2108–2121PubMedCrossRef
4.
Zurück zum Zitat Kitaichi M, Nagai S, Nishimura K, Itoh H, Asamoto H, Izumi T, Dail DH (1998) Pulmonary epithelioid haemangioendothelioma in 21 patients, including three with partial spontaneous regression. Eur Respir J 12:89–96PubMedCrossRef Kitaichi M, Nagai S, Nishimura K, Itoh H, Asamoto H, Izumi T, Dail DH (1998) Pulmonary epithelioid haemangioendothelioma in 21 patients, including three with partial spontaneous regression. Eur Respir J 12:89–96PubMedCrossRef
5.
Zurück zum Zitat Flaherty KT (2007) Sorafenib: delivering a targeted drug to the right targets. Expert Rev Anticancer Ther 7:617–626PubMedCrossRef Flaherty KT (2007) Sorafenib: delivering a targeted drug to the right targets. Expert Rev Anticancer Ther 7:617–626PubMedCrossRef
6.
Zurück zum Zitat Adnane L, Trail PA, Taylor I, Wilhelm SM (2006) Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature. Methods Enzymol 407:597–612PubMedCrossRef Adnane L, Trail PA, Taylor I, Wilhelm SM (2006) Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature. Methods Enzymol 407:597–612PubMedCrossRef
7.
Zurück zum Zitat Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, Cao Y, Shujath J, Gawlak S, Eveleigh D, Rowley B, Liu L, Adnane L, Lynch M, Auclair D, Taylor I, Gedrich R, Voznesensky A, Riedl B, Post LE, Bollag G, Trail PA (2004) BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64:7099–7109PubMedCrossRef Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, Cao Y, Shujath J, Gawlak S, Eveleigh D, Rowley B, Liu L, Adnane L, Lynch M, Auclair D, Taylor I, Gedrich R, Voznesensky A, Riedl B, Post LE, Bollag G, Trail PA (2004) BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64:7099–7109PubMedCrossRef
8.
Zurück zum Zitat Brown L, Tognazzi K, Dvorak HF, Harrist TJ (1996) Strong expression of kinase insert domain-containing receptor, a vascular permeability factor/vascular endothelial growth factor receptor in AIDS-associated Kaposi and cutaneous angiosarcoma. Am J Pathol 148:1065–1074PubMedCentralPubMed Brown L, Tognazzi K, Dvorak HF, Harrist TJ (1996) Strong expression of kinase insert domain-containing receptor, a vascular permeability factor/vascular endothelial growth factor receptor in AIDS-associated Kaposi and cutaneous angiosarcoma. Am J Pathol 148:1065–1074PubMedCentralPubMed
9.
Zurück zum Zitat Naito S, Shimizu K, Nakashima M, Ito T, Ito M, Yamashita S, Sekine I (2000) Overexpression of Ets-1 transcription factor in angiosarcoma of the skin. Pathol Res Pract 196:103–109PubMedCrossRef Naito S, Shimizu K, Nakashima M, Ito T, Ito M, Yamashita S, Sekine I (2000) Overexpression of Ets-1 transcription factor in angiosarcoma of the skin. Pathol Res Pract 196:103–109PubMedCrossRef
10.
Zurück zum Zitat Itakura E, Yamaoto H, Oda Y, Tsuneyoshi M (2008) Detection and characterization of vascular endothelia growth factors and their receptors in a series of angiosarcoma. J Surg Oncol 97:74–81PubMedCrossRef Itakura E, Yamaoto H, Oda Y, Tsuneyoshi M (2008) Detection and characterization of vascular endothelia growth factors and their receptors in a series of angiosarcoma. J Surg Oncol 97:74–81PubMedCrossRef
11.
Zurück zum Zitat LaMontagne KR Jr, Moses MA, Wiederschain D, Mahajan S, Holden J, Ghazizadeh H, Frank DA, Arbiser JL (2000) Inhibition of MAP kinases causes morphological reversion and dissociation between soft agar growth and in vivo tumorigenesis in angiosarcoma cells. Am J Pathol 157:1937–1945PubMedCrossRef LaMontagne KR Jr, Moses MA, Wiederschain D, Mahajan S, Holden J, Ghazizadeh H, Frank DA, Arbiser JL (2000) Inhibition of MAP kinases causes morphological reversion and dissociation between soft agar growth and in vivo tumorigenesis in angiosarcoma cells. Am J Pathol 157:1937–1945PubMedCrossRef
12.
Zurück zum Zitat Antonescu CR, Yoshida A, Guo T, Chang NE, Zhang L, Agaram NP, Qin LX, Brennan MF, Singer S, Maki RG (2009) KDR activating mutations in human angiosarcomas are sensitive to specific kinase inhibition. Cancer Res 69:71–79CrossRef Antonescu CR, Yoshida A, Guo T, Chang NE, Zhang L, Agaram NP, Qin LX, Brennan MF, Singer S, Maki RG (2009) KDR activating mutations in human angiosarcomas are sensitive to specific kinase inhibition. Cancer Res 69:71–79CrossRef
13.
Zurück zum Zitat Lahat G, Dhuka AR, Hallevi H, Xiao L, Zou C, Smith KD, Phung TL, Pollock RE, Benjamin R, Hunt KK, Lazar AJ, Lev D (2010) Angiosarcoma: clinical and molecular insights. Ann Surg 251:1098–1106PubMedCrossRef Lahat G, Dhuka AR, Hallevi H, Xiao L, Zou C, Smith KD, Phung TL, Pollock RE, Benjamin R, Hunt KK, Lazar AJ, Lev D (2010) Angiosarcoma: clinical and molecular insights. Ann Surg 251:1098–1106PubMedCrossRef
14.
Zurück zum Zitat Emamaullee JA, Edgar R, Toso C, Thiesen A, Bain V, Bigam D, Kneteman N, Shapiro AM (2010) Vascular endothelial growth factor expression in hepatic epithelioid hemangioendothelioma: implications for treatment and surgical management. Liver Transpl 16:191–197PubMedCrossRef Emamaullee JA, Edgar R, Toso C, Thiesen A, Bain V, Bigam D, Kneteman N, Shapiro AM (2010) Vascular endothelial growth factor expression in hepatic epithelioid hemangioendothelioma: implications for treatment and surgical management. Liver Transpl 16:191–197PubMedCrossRef
15.
Zurück zum Zitat Hatva E, Böhling T, Jääskeläinen J, Persico MG, Haltia M, Alitalo K (1996) Vascular growth factors and receptors in capillary hemangioblastomas and hemangiopericytomas. Am J Pathol 148:763–775PubMedCentralPubMed Hatva E, Böhling T, Jääskeläinen J, Persico MG, Haltia M, Alitalo K (1996) Vascular growth factors and receptors in capillary hemangioblastomas and hemangiopericytomas. Am J Pathol 148:763–775PubMedCentralPubMed
16.
Zurück zum Zitat Ray-Coquard I, Italiano A, Bompas E, Le Cesne A, Robin YM, Chevreau C, Bay JO, Bousquet G, Piperno-Neumann S, Isambert N, Lemaitre L, Fournier C, Gauthier E, Collard O, Cupissol D, Clisant S, Blay JY, Penel N, French Sarcoma Group (GSF/GETO) (2012) Sorafenib for patients with advanced angiosarcoma : a phase II trial from the French Sarcoma Group (GSF/GETO). Oncologist 17:260–266PubMedCentralPubMedCrossRef Ray-Coquard I, Italiano A, Bompas E, Le Cesne A, Robin YM, Chevreau C, Bay JO, Bousquet G, Piperno-Neumann S, Isambert N, Lemaitre L, Fournier C, Gauthier E, Collard O, Cupissol D, Clisant S, Blay JY, Penel N, French Sarcoma Group (GSF/GETO) (2012) Sorafenib for patients with advanced angiosarcoma : a phase II trial from the French Sarcoma Group (GSF/GETO). Oncologist 17:260–266PubMedCentralPubMedCrossRef
17.
Zurück zum Zitat Chevreau C, Le Cesne A, Ray-Coquard I, Italiano A, Cioffi A, Isambert N, Robin YM, Fournier C, Clisant S, Chaigneau L, Bay JO, Bompas E, Gauthier E, Blay JY, Penel N (2013) Sorafenib in patients with progressive epithelioid hemangioendothelioma: a phase 2 study by the Fench Sarcoma Group (GSF/GETO). Cancer. doi:10.1002/cncr.28109 PubMed Chevreau C, Le Cesne A, Ray-Coquard I, Italiano A, Cioffi A, Isambert N, Robin YM, Fournier C, Clisant S, Chaigneau L, Bay JO, Bompas E, Gauthier E, Blay JY, Penel N (2013) Sorafenib in patients with progressive epithelioid hemangioendothelioma: a phase 2 study by the Fench Sarcoma Group (GSF/GETO). Cancer. doi:10.​1002/​cncr.​28109 PubMed
18.
Zurück zum Zitat Tokuyama W, Mikami T, Masuzawa M, Okayasu I (2010) Autocrine and paracrine roles of VEGF/VEGFR-2 and VEGF-C/VEGFR63 signaling in angiosarcomas of the scalp and face. Hum Pathol 41:407–414PubMedCrossRef Tokuyama W, Mikami T, Masuzawa M, Okayasu I (2010) Autocrine and paracrine roles of VEGF/VEGFR-2 and VEGF-C/VEGFR63 signaling in angiosarcomas of the scalp and face. Hum Pathol 41:407–414PubMedCrossRef
19.
Zurück zum Zitat Lovet JM, Pena CE, Lathia CD, Shan M, Meinherdt G, Bruix J, SHARP Investigators Study Group (2012) Plasma biomarkers as predictors of outcome in patients with advanced hepatocellular carcinoma. Clin Cancer Res 18:2290–2300CrossRef Lovet JM, Pena CE, Lathia CD, Shan M, Meinherdt G, Bruix J, SHARP Investigators Study Group (2012) Plasma biomarkers as predictors of outcome in patients with advanced hepatocellular carcinoma. Clin Cancer Res 18:2290–2300CrossRef
20.
Zurück zum Zitat Pena C, Lathia C, Shan M, Escudier B, Bukowski RM (2010) Biomarkers predicting outcome in patients with advanced renal cell carcinoma: results from sorafenib phase III treatment approaches in renal cancer global evaluation trial. Clin Cancer Res 16:4853–4863PubMedCrossRef Pena C, Lathia C, Shan M, Escudier B, Bukowski RM (2010) Biomarkers predicting outcome in patients with advanced renal cell carcinoma: results from sorafenib phase III treatment approaches in renal cancer global evaluation trial. Clin Cancer Res 16:4853–4863PubMedCrossRef
21.
Zurück zum Zitat Raut CP, Boucher Y, Duda DG, Morgan JA, Quek R, Ancukiewicz M et al (2012) Effects of sorafenib on intra-tumoral interstitial fluid pressure and circulating biomarkers in patients with refractory sarcomas (NCI protocol 6948). PLoS One 7:e26331PubMedCentralPubMedCrossRef Raut CP, Boucher Y, Duda DG, Morgan JA, Quek R, Ancukiewicz M et al (2012) Effects of sorafenib on intra-tumoral interstitial fluid pressure and circulating biomarkers in patients with refractory sarcomas (NCI protocol 6948). PLoS One 7:e26331PubMedCentralPubMedCrossRef
22.
Zurück zum Zitat Sleijfer S, Gorlia T, Lamers C, Burger H, Blay JY, Le Cesne A et al (2012) Cytokine and angiogenic factors associated with efficacy and toxicity of pazopanib in advanced soft tissue sarcoma: an EORTC-STBSG study. Eur J Cancer 107:639–645 Sleijfer S, Gorlia T, Lamers C, Burger H, Blay JY, Le Cesne A et al (2012) Cytokine and angiogenic factors associated with efficacy and toxicity of pazopanib in advanced soft tissue sarcoma: an EORTC-STBSG study. Eur J Cancer 107:639–645
23.
Zurück zum Zitat Sleijfer S, Ouali M, Van Glabbeke M, Krarup-Hansen A, Rodenhuis S, Le Cesne A et al (2010) Prognostic and predictive factors for outcome to first-line ifosfamide-containing chemotherapy for adult patients with advanced soft tissue sarcomas: an exploratory, retrospective analysis on large series from the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG). Eur J Cancer 46:72–83PubMedCrossRef Sleijfer S, Ouali M, Van Glabbeke M, Krarup-Hansen A, Rodenhuis S, Le Cesne A et al (2010) Prognostic and predictive factors for outcome to first-line ifosfamide-containing chemotherapy for adult patients with advanced soft tissue sarcomas: an exploratory, retrospective analysis on large series from the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG). Eur J Cancer 46:72–83PubMedCrossRef
Metadaten
Titel
Low level of baseline circulating VEGF-A is associated with better outcome in patients with vascular sarcomas receiving sorafenib: an ancillary study from a phase II trial
verfasst von
Nicolas Penel
Isabelle Ray-Coquard
Christine Bal-Mahieu
Christine Chevreau
Axel Le Cesne
Antoine Italiano
Emmanuelle Bompas
Stéphanie Clisant
Brigitte Baldeyrou
Amélie Lansiaux
Yves-Marie Robin
Jacques-Olivier Bay
Sophie Piperno-Neumann
Jean-Yves Blay
Charles Fournier
Publikationsdatum
01.09.2014
Verlag
Springer International Publishing
Erschienen in
Targeted Oncology / Ausgabe 3/2014
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-013-0299-0

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