Chemotherapy in Endometrial Cancer

  • Domenica Lorusso
  • Mansoor Raza Mirza


Management of endometrial cancer has become more complex during the past 10 years for several reasons: changes in histological classification (type 1 vs. type 2) have affected surgical management, adjuvant therapy strategies deeply modified based on data from randomized trials and indications and modalities of lymphadenectomy have changed, even if therapeutic or simply prognostic role of lymphadenectomy remains to be defined.


  1. 1.
    Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.CrossRefGoogle Scholar
  2. 2.
    Weiderpass E, Antoine J, Bray FI, Oh JK, Arbyn M. Trends in corpus uteri cancer mortality in member states of the European Union. Eur J Cancer. 2014;50:1675–84.CrossRefGoogle Scholar
  3. 3.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29.CrossRefGoogle Scholar
  4. 4.
    Creasman WT, Odicino F, Maisonneuve P, et al. Carcinoma of the corpus uteri. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet. 2006;95(suppl 1):S105–43.CrossRefGoogle Scholar
  5. 5.
    Creutzberg CL, van Putten WL, Koper PC, et al. Surgery and postoperative radiotherapy versus surgery alone for patients with stage 1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post operative radiation therapy in endometrial carcinoma. Lancet. 2000;355:1404–11.CrossRefGoogle Scholar
  6. 6.
    Keys HM, Roberts JA, Brunetto VL, the Gynecologic Oncology Group, et al. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004;92:744–51.CrossRefGoogle Scholar
  7. 7.
    Aalders J, Abeler V, Kolstad P, Onsrud M. Postoperative external irradiation and prognostic parameters in stage I endometrial carcinoma: clinical and histopathologic study of 540 patients. Obstet Gynecol. 1980;56:419–27.Google Scholar
  8. 8.
    Onsrud M, Cvancarova M, Hellebust TP, Tropé CG, Kristensen GB, Lindemann K. Long-term outcomes after pelvic radiation for early-stage endometrial cancer. J Clin Oncol. 2013;31:3951–6.CrossRefGoogle Scholar
  9. 9.
    Creutzberg CL, Nout RA, Lybeert ML, the PORTEC Study Group, et al. Fifteen-year radiotherapy outcomes of the randomized PORTEC-1 trial for endometrial carcinoma. Int J Radiat Oncol Biol Phys. 2011;81:e631–8.CrossRefGoogle Scholar
  10. 10.
    Blake P, Swart AM, Orton J, the ASTEC/EN.5 Study Group, et al. Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis. Lancet. 2009;373:137–46.CrossRefGoogle Scholar
  11. 11.
    Nout RA, Smit VTHB, Putter H, the PORTEC Study Group, et al. Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial. Lancet. 2010;375:816–23.CrossRefGoogle Scholar
  12. 12.
    Sorbe B, Horvath G, Andersson H, Boman K, Lundgren C, Pettersson B. External pelvic and vaginal irradiation versus vaginal irradiation alone as postoperative therapy in medium-risk endometrial carcinoma—a prospective randomized study. Int J Radiat Oncol Biol Phys. 2012;82:1249–55.CrossRefGoogle Scholar
  13. 13.
    Kong A, Johnson N, Kitchener HC, Lawrie TA. Adjuvant radiotherapy for stage I endometrial cancer: an updated Cochrane systematic review and meta-analysis. J Natl Cancer Inst. 2012;104:1625–34.CrossRefGoogle Scholar
  14. 14.
    Morrow CP, Bundy BN, Homesley HD, et al. Doxorubicin as an adjuvant following surgery and radiation therapy in patients with high-risk endometrial carcinoma, stage I and occult stage II: a Gynecologic Oncology Group study. Gynecol Oncol. 1990;36:166Y171.CrossRefGoogle Scholar
  15. 15.
    Susumu N, Sagae S, Udagawa Y, the Japanese Gynecologic Oncology Group, et al. Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- and high-risk endometrial cancer: a Japanese Gynecologic Oncology Group study. Gynecol Oncol. 2008;108:226–33.CrossRefGoogle Scholar
  16. 16.
    Maggi R, Lissoni A, Spina F, et al. Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial. Br J Cancer. 2006;95:266–71.CrossRefGoogle Scholar
  17. 17.
    Randall ME, Filiaci VL, Muss H, the Gynecologic Oncology Group study, et al. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2006;24:36–44.CrossRefGoogle Scholar
  18. 18.
    McMeekin DS, Filiaci VL, Thigpen JT, Gallion HH, Fleming GF, Rodgers WH, the Gynecologic Oncology Group study. The relationship between histology and outcome in advanced and recurrent endometrial cancer patients participating in first-line chemotherapy trials: a Gynecologic Oncology Group study. Gynecol Oncol. 2007;106:16–22.CrossRefGoogle Scholar
  19. 19.
    Hogberg T, Signorelli M, de Oliveira CF, et al. Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer—results from two randomised studies. Eur J Cancer. 2010;46:2422–31.CrossRefGoogle Scholar
  20. 20.
    Kuoppala T, Mäenpää J, Tomas E, et al. Surgically staged high-risk endometrial cancer: randomized study of adjuvant radiotherapy alone vs. sequential chemo-radiotherapy. Gynecol Oncol. 2008;110:190–5.CrossRefGoogle Scholar
  21. 21.
    Johnson N, Bryant A, Miles T, Hogberg T, Cornes P. Adjuvant chemotherapy for endometrial cancer after hysterectomy. Cochrane Database Syst Rev. 2011;(10):CD003175.
  22. 22.
    Matai D, et al. GOG-258: randomized phase III trial of cisplatin and tumor volume–directed irradiation followed by carboplatin and paclitaxel vs carboplatin and paclitaxel for optimally debulked, advanced EC. J Clin Oncol. 2017;35(suppl):Abstract 5505.CrossRefGoogle Scholar
  23. 23.
    De Boer SM, et al. PORTEC-3: adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): an open-label, multicentre, randomised, phase 3 trial. J Clin Oncol. 2017;35(suppl):Abstract 5504.Google Scholar
  24. 24.
    de Boer SM, Powell ME, Mileshkin L, the PORTEC Study Group, et al. Toxicity and quality of life after adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2016; Scholar
  25. 25.
    Mirza, et al. ENGOT-EN2/DGCG: chemotherapy or observation in stage I-II intermediate or high risk endometrial cancer. NCT01244789.Google Scholar
  26. 26.
    Creutzberg CL, van Putten WL, Koper PC, PORTEC Study Group, et al. Survival after relapse in patients with endometrial cancer: results from a randomized trial. Gynecol Oncol. 2003;89:201–9.CrossRefGoogle Scholar
  27. 27.
    Del Carmen MG, Boruta DM II, Schorge JO. Recurrent endometrial cancer. Clin Obstet Gynecol. 2011;54:266–77.CrossRefGoogle Scholar
  28. 28.
    Humber CE, Tierney JF, Symonds RP, et al. Chemotherapy for advanced, recurrent or metastatic endometrial cancer: a systematic review of Cochrane collaboration. Ann Oncol. 2007;18:409–20.CrossRefGoogle Scholar
  29. 29.
    Fleming GF, Brunetto VL, Celia D, et al. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2004;22:2159–66.CrossRefGoogle Scholar
  30. 30.
    Miller D, Filiaci V, Fleming G, et al. Late-breaking abstract 1: randomized phase III noninferiority trial of first line chemotherapy for metastatic or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2012;125:771.CrossRefGoogle Scholar
  31. 31.
    Meric-Bernstam F, Gonzalez-Angulo AM. Targeting the mTOR signaling network for cancer therapy. J Clin Oncol. 2009;27:2278–87.CrossRefGoogle Scholar
  32. 32.
    Oza AM, Elit L, Tsao MS, et al. Phase II study of temsirolimus in women with recurrent or metastatic endometrial cancer: a trial of the NCIC Clinical Trials Group. J Clin Oncol. 2011;29:3278–85.CrossRefGoogle Scholar
  33. 33.
    Slomovitz BM, Lu KH, Johnston T, et al. A phase 2 study of the oral mammalian target of rapamycin inhibitor, everolimus, in patients with recurrent endometrial carcinoma. Cancer. 2010;116:5415–9.CrossRefGoogle Scholar
  34. 34.
    Naing A, Aghajanian C, Raymond E, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics of AZD8055 in advanced solid tumours and lymphoma. Br J Cancer. 2012;107:1093–9.CrossRefGoogle Scholar
  35. 35.
    Aghajanian C, Sill MW, Darcy KM, et al. Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2011;29:2259–65.CrossRefGoogle Scholar
  36. 36.
    O’Malley D, McCann G, Fowler J, et al. A phase II evaluation of carboplatin/paclitaxel/bevacizumab in the treatment of advanced stage endometrial carcinoma. Presented at the 42nd annual meeting on women’s cancer, Austin; 2013.Google Scholar
  37. 37.
    Aghajanian C, Filiaci VL, Dizon DS, et al. A randomized phase II study of paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus and ixabepilone/carboplatin/bevacizumab as initial therapy for measurable stage III or IVA, stage IVB or recurrent endometrial cancer, GOG-86P. J Clin Oncol. 2015;33(suppl):abstr 5500.CrossRefGoogle Scholar
  38. 38.
    Lorusso D, Ferrandina G, Colombo N, et al. Randomized phase II trial of carboplatin-paclitaxel (CP) compared to carboplatin-paclitaxel-bevacizumab (CP-B) in advanced (stage III-IV) or recurrent endometrial cancer: the MITO END-2 trial. J Clin Oncol. 2015;33(suppl):abstr 5502.CrossRefGoogle Scholar
  39. 39.
    Mirza, et al. ENGOT-EN1/FANDANGO: a randomized phase II trial of first-line combination chemotherapy with nintedanib/placebo for patients with advanced or recurrent endometrial cancer. NCT02730416.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Domenica Lorusso
    • 1
  • Mansoor Raza Mirza
    • 2
  1. 1.Fondazione Policlinico Universitario A GemelliRomeItaly
  2. 2.Department of OncologyRigshospitalet, Copenhagen University HospitalCopenhagenDenmark

Personalised recommendations