Skip to main content

Advertisement

SpringerLink
Log in

Targeted therapies for gynecologic malignancies

  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Despite the enormous promise that targeted therapies hold for patients with gynecologic malignancies, it is far too early to recommend any targeted therapy outside of a clinical trial. There remains considerable work to be done before targeted therapies will have a significant role in this patient population. We have learned that different tumor types express different targets, but that the mere expression of a target does not necessarily correlate with benefit from the use of the targeted agent. No less important is the challenge of determining how these agents should be studied in clinical trials, and what constitutes an active agent. To document efficacy, targeted agents would hopefully produce response (ie, shrinkage of measurable tumor), but as cytostatic agents, the ability to delay tumor growth or slow the development of symptoms would be clinically important. Combining targeted therapies with cytotoxic agents, radiation, or other targeted therapies may be important areas for study, but it is essential to demonstrate the additive or synergistic effect of the targeted therapy to an already established active one. This review covers strategies used to develop targeted agents, reviews available targeted therapies, and suggests potential roles in the treatment of gynecologic cancers.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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. American Cancer Society:Cancer Statistics 2004. Accessible at http://www.cancer.org/docroot/home/index.asp. Accessed November 15, 2004.

  2. Savage D, Antman K:Imatinib mesylate-a new oral targeted therapy. New Engl J Med 2002, 356:683–693. Excellent review of targets and use of imatinib.

    Article  Google Scholar 

  3. Ball HG, Blessing JA, Lentz SS, Mutch DG:A phase II trial of paclitaxel in patients with advanced or recurrent adenocarcinoma of the endometrium:A Gynecologic Oncology Group Study. Gynecol Oncol 1996, 62:278–281.

    Article  PubMed  CAS  Google Scholar 

  4. McMeekin DS, Sill M, Benbrook D, et al.:A phase II study of thalidomide in patients with recurrent or persistent endometrial carcinoma:A Gynecologic Oncology Group (GOG) Study [abstract]. Gynecol Oncol 2004, 92:438.

    Google Scholar 

  5. Eisenhauer E:Phase I and II trials of novel anticancer agents:endpoints, efficacy, and existentialism. Ann Oncol 1998, 9:1047–1052. Interesting discussion of study designs and the best way to evaluate targeted therapies.

    Article  PubMed  CAS  Google Scholar 

  6. Fox E, Curt G, Balis F:Clinical trial design for targetbased therapy. Oncologist 2002, 7:401–409.

    Article  PubMed  CAS  Google Scholar 

  7. Druker B:Molecularly targeted therapy:have the floodgates opened? Oncologist 2004, 9:357–360.

    Article  PubMed  Google Scholar 

  8. Rosner G, Ratain M:Randomized discontinuation design:Applications to cytostatic antineoplastic agents. J Clin Oncol 2002, 20:4478–4484.

    Article  PubMed  CAS  Google Scholar 

  9. Macnard S, Pupa S, Campiglio M, Tagliabue E:Biologic and therapeutic role of HER2 in cancer. Oncogene 2003, 22:6570–6578.

    Article  CAS  Google Scholar 

  10. Cobleigh MA, Vogel CL, Tripathy D, et al.:Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2 overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 1999, 17:2639–2648.

    PubMed  CAS  Google Scholar 

  11. Slamon DJ, Leyland-Jones B, Shak S, et al.:Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. New Engl J Med 2001, 344:783–792.

    Article  PubMed  CAS  Google Scholar 

  12. Langer CJ, Stephenson P, Thor A, et al.:Trastuzumab in the treatment of advanced non-small-cell lung cancer:is there a role? Focus on Eastern Cooperative Oncology Group Study 2598. J Clin Oncol 2004, 22:1180–1187.

    Article  PubMed  CAS  Google Scholar 

  13. Hellstrom I, Goodman G, Pullman J, et al.:Overexpression of HER2 in ovarian carcinomas. Cancer Res 2001, 61:2420–2423.

    PubMed  CAS  Google Scholar 

  14. Bookman MA, Darcy KM, Clark-Pearson D, etal:Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2:a phase II trial of the Gynecologic Oncology Group. J Clin Oncol 2003, 21:283–290.

    Article  PubMed  CAS  Google Scholar 

  15. Grushko TA, Ridderstrale K, Olopade OI: Identification of HER2/NEU oncogene amplification by fluorescence in situ hybridization in endometrial carcinoma from patients included in Gynecologic Oncology Group trial 177 [abstract]. Proc Am Soc Clin Oncol 2003, 22:468.

    Google Scholar 

  16. Santin A:HER2/neu overexpression:has the Achilles’ heel of uterine serous papillary carcinoma been exposed? Gynecol Oncol 2003, 88:263–265.

    Article  PubMed  CAS  Google Scholar 

  17. Slomovitz B, Broaddus R, Burke T, et al.:HER2/neu overexpression and amplification in uterine papillary serous carcinoma. J Clin Oncol 2004, 22:3126–3132.

    Article  PubMed  CAS  Google Scholar 

  18. Fleming GF, Sill MA, Thigpen JT, et al.:Phase II evaluation of trastuzumab in patients with advanced or recurrent endometrial carcinoma:A report on GOG 181B [abstract]. Proc Am Soc Clin Oncol 2003, 22:453.

    Google Scholar 

  19. El Rayes B, LoRusso P:Targeting the epidermal growth factor receptor. Br J Cancer 2004, 91:418–424.

    Article  CAS  Google Scholar 

  20. Shin DM, Donato NJ, Perez-Soler R, et al.:Epidermal growth factor receptor-targeted therapy with C225 and cisplatin in patients with head and neck cancer. Clin Cancer Res 2001, 7:1204–1213.

    PubMed  CAS  Google Scholar 

  21. Burtness BA, Li Y, Flood W, et al.:Phase III trial comparing cisplatin plus placebo to cisplatin plus antiepidermal growth factor antibody C225 in patients with recurrent/metastatic head and neck cancer [abstract]. Proc Am Soc Clin Oncol 2002, 21.

  22. Bartlett JM, Langdon SP, Simpson BJ, et al.:The prognostic value of epidermal growth factor receptor mRNA expression in primary ovarian cancer. Br J Cancer 1996, 73:301–306.

    PubMed  CAS  Google Scholar 

  23. Ilekis JV, Connor JP, Prins GS, et al.:Expression of epidermal growth factor and androgen receptors in ovarian cancer. Gynecol Oncol 1997, 66:250–254.

    Article  PubMed  CAS  Google Scholar 

  24. Kersemakers A, Fleuren G, Kenter G, et al.:Oncogene alterations in carcinomas of the uterine cervix:overexpression of the epidermal growth factor receptor is associated with poor prognosis. Clin Cancer Res 1999, 5:577–586.

    Google Scholar 

  25. Miturski R, Semczuk A, Postawski K, et al.:Epidermal growth factor receptor immunostaining and epidermal growth factor receptor-tyrosine kinase activity in proliferative and neoplastic human endometrium. Tumour Biol 2000, 21:358–366.

    Article  PubMed  CAS  Google Scholar 

  26. Ranson M, Wardell S:Geftinib, a novel, orally administered agent for the treatemtn of cancer. J Clin Pharm Ther 2004, 29:95–103.

    Article  PubMed  CAS  Google Scholar 

  27. Fukuoka M, Yano S, Giaccone G, et al.:Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer. J Clin Oncol 2003, 21:2237–2246.

    Article  PubMed  CAS  Google Scholar 

  28. Kris MG, Natale RB, Herbst RS, et al.:Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer:a randomized trial. JAMA 2003, 290:2149–2158.

    Article  PubMed  CAS  Google Scholar 

  29. Lynch T, Bell D, Sordella R, et al.:Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small cell lung cancer to genfitinib. New Engl J Med 2004, 350:2129–2139.

    Article  PubMed  CAS  Google Scholar 

  30. Herbst RS, Giaccone G, Schiller JH, et al.:Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer:a phase III trial-INTACT-2. J Clin Oncol 2004, 22:785–794.

    Article  PubMed  CAS  Google Scholar 

  31. Giaccone G, Herbst RS, Manegold C, et al.:Gefitinib in combination with gemcitabine and cisplatin in advanced non-small cell lung cancer:a phase III trial-INTACT-1. J Clin Oncol 2004, 22:778–784.

    Article  CAS  Google Scholar 

  32. Ciardiello F, Caputo R, Bianco R, et al.:Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839, an epidermal growth factor receptor-selective tyrosine kinase inhibitor. Clin Cancer Res 2000, 6:2053–63.

    PubMed  CAS  Google Scholar 

  33. Lorusso PM:Phase I studies of ZD1839 in patients with common solid tumors. Sem Oncol 2003, 30(Suppl 1):21–29.

    Article  CAS  Google Scholar 

  34. Finkler N, Gordon A, Crozier M, et al.:Phase II evaluation of OSI-774, a potent antagonist of the EGFR-TK in patients with advanced ovarian carcinoma [abstract]. Proc Am Soc Clin Oncol 2001, 20.

  35. Henriksen R, Funa K, Wilander E, et al.:Expression and prognostic significance of platelet derived growth factor and its receptors in epithelial ovarian neoplasms. Cancer Res 1993, 53:4550–4554.

    PubMed  CAS  Google Scholar 

  36. Slomovitz B, Broaddus R, Schmandt R, et al.:Expression of imatinib mesylate targeted kinases in endometrial cancer. Gynecol Oncol 2004, 95:32–36.

    Article  PubMed  CAS  Google Scholar 

  37. Leath CA, Straughn JM, Conner MG, et al.:Immunohistochemical evaluation of the c-Kit proto-oncogene in sarcomas of the uterus. J Reprod Med 2004, 49:71–75.

    PubMed  Google Scholar 

  38. Zondor P, Medina P:Bevacizumab:an angiogenesis inhibitor with efficacy in colorectal and other malignancies. Ann Pharmacother 2004, 38:1258–1264.

    Article  PubMed  CAS  Google Scholar 

  39. Kabbinavar F, Hurwitz H, Fehrenbacher L, et al.:Phase II, randomized trial comparing bevacizumab plus fluorouracil/leucovorin with fluorouracil/leucovorin alone in patients with metastatic colorectal cancer. J Clin Oncol 2003; 21:60–65.

    Article  PubMed  CAS  Google Scholar 

  40. Johnson DH, Kabbinavar F, Fehrenbacher L, et al.:A phase II, randomized trial comparing bevacizumab plus carboplatin/paclitaxel with carboplatin/ paclitaxel alone in patients with locally advanced or metastatic non-small cell lung cancer. J Clin Oncol 2004, 22:2184–2191.

    Article  PubMed  CAS  Google Scholar 

  41. Yoneda J, Kuniyasu H, Crispens MA, et al.:Expression of angiogenesis-related genes and progression of human ovarian carcinomas in nude mice. J Natl Cancer Inst 1998, 90:447–454.

    Article  PubMed  CAS  Google Scholar 

  42. Nakanishi Y, Kodama J, Yoshinouchi M, et al.:The expression of vascular endothelial growth factor and transforming growth factor-beta associates with angiogenesis in epithelial ovarian cancer. Int J Gynecol Pathol 1997, 16:256–262.

    Article  PubMed  CAS  Google Scholar 

  43. Richardson P:Clinical update:proteasome inhibitors in hematologic malignancies. Cancer Treat Rev 2003, 29(Suppl):33–39.

    Article  PubMed  CAS  Google Scholar 

  44. Franks M, Macpherson G, Figg W: Thalidomide. Lancet 2004, 363:1802–1811. Reviews thalidomide as an anti-angiogenic agent

    Article  PubMed  CAS  Google Scholar 

  45. Singhal S, Mehta J, Desikan R, et al.:Antitumor activity of thalidomide in refractory multiple myeloma. New Engl J Med 1999, 341:1565–1571.

    Article  PubMed  CAS  Google Scholar 

  46. Abramson N, Stokes PK, Luke M, et al.:Ovarian and papillary-serous peritoneal carcinoma:pilot study with thalidomide. J Clin Oncol. 2002;20:1147–1149.

    Article  PubMed  CAS  Google Scholar 

  47. Francisco R, Ezekiel MP, Spencer SA, et al.:Phase I study of anti-epidermal growth factor receptor antibody cetuximab in combination with radiation therapy in patients with advanced head and neck cancer. J Clin Oncol 2001, 19:3234–3243.

    Google Scholar 

  48. Shintani S, Kiyota A, Mihara M, et al.:Enhancement of radiosensitivity in head and neck cancer cells by ZD1839, a selective epidermal growth factor receptor tyrosine kinase inhibitor. Am J Clin Oncol 2003, 26:150–156.

    Article  Google Scholar 

  49. Zhu AX, Willett CG:Chemotherapeutic and biologic agents as radiosensitizers in rectal cancer. Sem Rad Oncol 2003, 13:454–468.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Oklahoma-HSC, PO Box 26901, 73190, Oklahoma City, OK, USA

    D. Scott McMeekin (MD)

Authors
  1. Johnny Hyde
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Scott McMeekin
    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

Hyde, J., McMeekin, D.S. Targeted therapies for gynecologic malignancies. Curr. Treat. Options in Oncol. 6, 121–132 (2005). https://doi.org/10.1007/s11864-005-0020-3

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11864-005-0020-3

Keywords

Search

Navigation