Preview

Bone and soft tissue sarcomas, tumors of the skin

Advanced search

Antiangiogenic therapy in the treatment of soft tissue sarcomas

Abstract

Soft tissue sarcomas are tumors with high level of vascularization, so angiogenesis plays important role in tumor development and metastasis. Inhibitors of angiogenesis: bevacisumab, sunitinib, sorafenib were studied in clinical trials for the treatment of soft tissue sarcomas. During phase II clinical study the lack of efficacy of monotherapy with bevacisumab, sunitinib, sorafenib was proved. Phase III study PALETTE showed efficacy and safety of pazopanib usage in patients with advanced soft tissue sarcomas who were pretreated with chemotherapy (noGIST, noadipocytic sarcomas). It seems promising to continue the study of efficacy and safety of combination of targeted agents and conventional chemotherapy.

About the Authors

A. A. Fedenko
Moscow, Russian Federation
Russian Federation


V. A. Gorbunova
Moscow, Russian Federation
Russian Federation


References

1. Carmeliet P., Jain R.K. Angiogenesis in cancer and other diseases. Nature. 2000, v. 407, p. 249-257.

2. Dirix L.Y., Vermeulen P., De Wever I., Van Oosterom A.T. Soft tissue sarcoma in adults. Curr. Opin. Oncol. 1997, v. 9, p.348-359.

3. Pakosi E., Goussia A.C., Tsekerisi G. et al. Expression of vascular endothelial growth factor and its receptor, KDR/ Flk-1, in soft tissue sarcomas. Anticancer Res. 2005, v. 25, p.3591-3596.

4. DuBois S., Demetri G. Markers of angiogenesis and clinical features in patients with sarcoma. Cancer. 2007, v. 109 (5), p. 813-819.

5. Hayes A.J., Mostyn-Jones A., Koban M.U. et al. Serum vascular endothelial growth factor as a tumour marker in soft tissue sarcoma. Br. J. Surg. 2004, v. 91, p. 242-247.

6. Kilvaer T.K., Valkov A., Sorbye S. et al. Profiling of VEGFs and VEGFRs as prognostic factors in soft tissue sarcoma: VEGFR-3 is an independent predictor of poor prognosis. PLoS ONE. 2010, v. 5 (12), E15368.

7. Sleijfer S., Ray-Coquard I., Papai Z. et al. Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a Phase II study from the European Organization for Research and Treatment

8. Casali P.G., Blay J.Y Soft tissue sarcomas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2010, v. 21 (Suppl. 5), р. 198-203.

9. Potti A., Ganti A.K., Tendulkar K. et al. Determination of vascular endothelial growth factor (VEGF) overexpression in soft tissue sarcomas and the role of overexpression in leiomyosarcoma. J. Cancer Res. Clin. Oncol. 2004, v. 130, p. 52-56.

10. Hayes A.J., Mostyn-Jones A., Koban M.U. et al. Serum vascular endothelial growth factor as a tumour marker in soft tissue sarcoma. Br. J. Surg. 2004, v. 91, p. 242-247.

11. Rini B.I. Vascular endothelial growth factor-targeted therapy in renal cell carcinoma: current status and future directions. Clin. Cancer Res. 2007, v. 13, p. 1098-1106.

12. D’Adamo D.R., Anderson S.E., Albritton K. et al. Phase II study of doxorubicin and bevacizumab for patients with metastatic soft tissue sarcomas. J. Clin. Oncol. 2005, v. 23, p. 7135-7142.

13. Robert G. Maki et al. Phase II study of Sorafenib in Patients With Metastatic or Recurrent Sarcomas JCO. 2009, July 1, v. 27, No. 19, p. 3133-3140.

14. Vigil C.E., Chiaporri A.A., Williams C.A. et al: Phase II study of sunitinib malate (SM) in patients with metastatic and/or surgically unresectable nonGIST soft tissue sarcomas. J. Clin. Oncol. 2008, v. 26 (May 20, suppl.; abstr. 10535).

15. Keohan M.L. et al. Continuous daily dosing (CDD) of sunitinib (SU) in patients with metastatic soft tissue sarcomas (STS) other than GIST: Results of a phase II trial. J. Clin. Oncol. 2008, v. 26 (May 20, suppl.; abstr. 10533).

16. Hamberg P., Verweij J., Sleijfer S. (Pre-)clinical pharmacology and activity of pazopanib, a novel multikinase angiogenesis inhibitor. Oncologist. 2010, v. 15, p. 539-547.

17. Kumar R., Knick V.B., Rudolph S.K. et al. Pharmacokinetic - pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity. Mol. Cancer Ther. 2007, v. 6, p. 2012-2021.

18. Gotink K.J., Verheul H.M.W. Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism of action? Angiogenesis. 2010, v. 13 (1), p. 1-14.

19. Hurwitz H.I., Dowlati A., Saini S. et al. Phase I trial of pazopanib in patients with advanced cancer. Clin. Cancer Res. 2009, v. 15, p. 4220-4227.

20. Hutson T.E., Davis I.D., Machiels J.P. et al. Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. J. Clin. Oncol. 2010, v. 28, p. 475-480.

21. Sternberg C.N., Davis I.D., Mardiak J. et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized Phase III trial. J. Clin. Oncol. 2010, v. 28, p. 1061-1068.

22. Van Der Graaf W.T., Blay J., Chawla S.P et al. PALETTE: a randomized, double-blind, Phase III trial of pazopanib versus placebo in patients (pts) with soft-tissue sarcoma (STS) whose disease has progressed during or following prior chemotherapy - an EORTC STBSG Global Network Study (EORTC 62072). J. Clin. Oncol. 2011, v. 29 (18 suppl.; abstract LBA10002).

23. Van Der Graaf W.T., Blay J., Chawla S.P et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomized, double-blind, placebo-controlled phase 3 trial Lancet. 2012, May 19, v. 379 (9829), p. 1879-1886. Epub. 2012, May 16.

24. Kuhnen C., Lehnhardt M., Tolnay E. et al. Patterns of expression and secretion of vascular endothelial growth factor in malignant soft-tissue tumours. J. Cancer Res. Clin. Oncol. 2000, v. 126, p. 219-225.

25. Sleijfer S., van der Graaf W.T., Blay J.Y. Angiogenesis Inhibition in Non-GIST Soft Tissue Sarcomas. Oncologist. 2008, v. 13, p. 1193-1200.

26. Jain R.K. Normalizing tumor vasculature with anti-angiogenic therapy: A new paradigm for combination therapy. Nat. Med. 2001, v. 7, p. 987-989.

27. Wildiers H. et al. Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11. Br. J. Cancer. 2003, v. 88, p. 1979-1986.


Review

For citations:


Fedenko A.A., Gorbunova V.A. Antiangiogenic therapy in the treatment of soft tissue sarcomas. Bone and soft tissue sarcomas, tumors of the skin. 2012;(3):33-39. (In Russ.)

Views: 113


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2219-4614 (Print)
ISSN 2782-3687 (Online)