Skip to main content

Advertisement

SpringerLink
Log in

Systemic therapy for advanced soft-tissue sarcomas

  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

The field of oncology is experiencing a paradigm shift from broad-spectrum cytotoxic therapies to more specific molecularly based targeted therapies. The activity of imatinib mesylate in chronic myelogenous leukemia and gastrointestinal stromal tumors (GIST) has reinforced our faith in translational research and its potential impact on the cure of cancer and improvement in quality of life for patients. This breakthrough has been particularly exciting for the field of sarcoma and for patients with advanced GIST, for whom no other effective therapy was available. Unfortunately, as is becoming increasingly clear, cancer is a very complex problem with multiple mechanisms and pathways that function either independently or interdependently enabling cell survival. We are therefore far away from having solved the problem. Attempts at refining the currently available therapeutic armamentarium to maximize the therapeutic index (dose intensification with growth factor support) must continue in parallel with laboratory-based research identifying critical targets to be inhibited or blocked. Identification of new agents with some activity, such as gemcitabine and ecteinascidin (ET-743), is also of paramount importance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Miettinen M, Sarlomo-Rikala M, Lasota J: Gastrointestinal stromal tumors: recent advances in understanding of their biology. Hum Pathol 1999, 30:1213–1220. A review of the changes in nomenclature and molecular events in GISTs.

    Article  PubMed  CAS  Google Scholar 

  2. Hirota S, Isozaki K, Moriyama Y, et al.: Gain of function mutation of c-kit in human gastrointestinal stromal tumors. Science 1998, 279:577–580. Describes the pathogenetic event in the development of GISTs that forms the basis for targeted therapy with imatinib mesylate.

    Article  PubMed  CAS  Google Scholar 

  3. Lasota J, Jasinski M, Sarlomo-Rikala M, et al.: Mutations in exon 11 of c-kit occur preferentially in malignant versus benign GISTs and do not occur in leiomyomas or leiomyosarcomas. Am J Pathol 1999, 154:53–60. Defines the distinguishing characteristics of the exon 11 mutations as specific to malignant variants of GISTs.

    PubMed  CAS  Google Scholar 

  4. Lasota J, Wozniak A, Sarlomo-Rikala M, et al.: Mutations in exons 9 and 11 of KIT gene are rare events in GISTs: a study of 200 cases. Am J Pathol 2000, 157:1091–1095.

    PubMed  CAS  Google Scholar 

  5. Plager C, Papadopoulos NEJ, Salem P, Benjamin RS: Adriamycin based chemotherapy for leiomyosarcoma of the stomach and small bowel [abstract]. Proc ASCO 1991, 10:352.

    Google Scholar 

  6. Patel SR, Legha SS, Salem PA, et al.: Evaluation of ifosfamide in metastatic leiomyosarcomas of gastrointestinal origin [abstract]. Proc ASCO 1991, 10:352.

    Google Scholar 

  7. Mavligit GM, Zukiwski AA, Salem PA, et al.: Regression of hepatic metastases from gastrointestinal leiomyosarcoma after hepatic arterial chemoembolization. Cancer 1991, 68:321–323.

    Article  PubMed  CAS  Google Scholar 

  8. Tuveson DT, Fletcher CDM, Singer S, et al.: STI571 inactivation of the GIST c-KIT oncoprotein: biological and clinical implications. Oncogene 2001, 20:5054–5058.

    Article  PubMed  CAS  Google Scholar 

  9. Joensuu H, Roberts PJ, Sarlomo-Rikala M, et al.: Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal tumor. N Engl J Med 2001, 344:1052–1056.

    Article  PubMed  CAS  Google Scholar 

  10. van Oosterom AT, Judson I, Verweij J, et al.: Safety and efficacy of STI 571 in metastatic gastrointestinal stromal tumours: a phase 1 study. Lancet 2001, 358:1421–1423. Phase I toxicity data and evidence of activity in GISTs are presented in this report.

    Article  PubMed  Google Scholar 

  11. Blanke CD, von Mehren M, Joensuu H, et al.: Evaluation of the safety and efficacy of an oral molecularly-targeted therapy STI 571, in patients with unresectable or metastatic gastrointestinal stromal tumors expressing C-KIT (CD 117) [abstract]. Proc ASCO 2001, 20:1a. The phase II data presented in this report confirm activity seen in the phase I study.

    Google Scholar 

  12. O’Bryan R, Baker L, Gottlieb J, et al.: Dose response evaluation of Adriamycin in human neoplasia. Cancer 1977, 39:1940–1948.

    Article  PubMed  CAS  Google Scholar 

  13. Patel SR, Vadhan-Raj S, Papadopoulos N, et al.: High dose ifosfamide in bone and soft tissue sarcomas: results of phase II and pilot studies-dose response and scheduled dependence. J Clin Oncol 1997, 15:2378–2384.

    PubMed  CAS  Google Scholar 

  14. Patel SR, Vadhan-Raj S, Burgess MA, et al.: Results of two consecutive trials of dose intensive chemotherapy with doxorubicin and ifosfamide is highly active in patients with soft tissue sarcomas. Am J Clin Oncol 1998, 21:317–321.

    Article  PubMed  CAS  Google Scholar 

  15. Le Cesne A, Judson I, Crowther D, et al.: Randomized phase 3 study comparing conventional-dose doxorubicin plus ifosfamide versus high-dose doxorubicin plus ifosfamide plus recombinant GM-CSF in advanced soft-tissue sarcomas: a trial of the EORTC/STBSG. J Clin Oncol 2000, 18:2676–2684.

    PubMed  Google Scholar 

  16. Frustaci S, Gherlinzoni F, De Paoli A, et al.: Adjuvant chemotherapy for adult soft-tissue sarcomas of the extremities and girdles: results of the Italian Randomized cooperative group trial. J Clin Oncol 2001, 19:1238–1247. This report gives strong evidence supporting the use of dose-intensive therapy with anthracycline and ifosfamide with growth factor support in appropriately selected patients with high-risk extremity sarcomas.

    PubMed  CAS  Google Scholar 

  17. Patel SR, Gandhi V, Jenkins J, et al.: Phase 2 clinical investigation of gemcitabine in advanced soft-tissue sarcomas and window evaluation of dose rate on gemcitabine triphosphate accumulation. J Clin Oncol 2001, 19:3483–3489. Trial describing encouraging activity in soft-tissue sarcomas.

    PubMed  CAS  Google Scholar 

  18. Delaloge S, Yovine A, Taamma A, et al.: Ecteinascidin-743: a marine-derived compound in advanced, pretreated sarcoma patients. Preliminary evidence of activity. J Clin Oncol 2001, 19:1248–1255. This report describes encouraging activity of another drug in sarcomas.

    PubMed  CAS  Google Scholar 

  19. Lecesne A, Blay JY, Judson I, et al.: A new active drug in adult soft-tissue sarcomas: STBSG-EORTC phase 2 trial [abstract]. Sarcoma 2001, S36:115a.

    Google Scholar 

  20. Demetri GD, Manola J, Harmon D, et al.: Ecteinascidin-743 induces durable responses and promising 1-year survival rates in soft-tissue sarcomas: final results of phase 2 and pharmacokinetic studies in the USA [abstract]. Proc ASCO 2001, 20:352a.

    Google Scholar 

  21. Patel SR, Jenkins J, Papadopoulos NE, et al.: Pilot study of Vitaxin—an angiogenesis inhibitor—in patients with advanced leiomyosarcomas. Cancer 2001, 92:1347–1348.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Sarcoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 450, 77030, Houston, TX, USA

    Shreyaskumar R. Patel MD

Authors
  1. Shreyaskumar R. Patel MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Patel, S.R. Systemic therapy for advanced soft-tissue sarcomas. Curr Oncol Rep 4, 299–304 (2002). https://doi.org/10.1007/s11912-002-0005-3

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11912-002-0005-3

Keywords

Search

Navigation