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Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Twenty percent of women with endometrial cancer will die from it, predominantly from systemic spread. Chemotherapy is, therefore, needed both for “high risk” women at diagnosis (stages III and IV–all histologies; stage II Clear Cell or grade 3; Papillary Serous or MMMT, irrespective of stage) and for relapsers, unless grade 1, when hormones are a preferable initial option. The most active single agents are: the anthracyclines, taxanes and platins; response rates 17–37, 21–67 and 13–14%, respectively. Combinations have proven to be superior in terms of relapse but not survival. Taxane-/platin-containing regimens are the phase III proven best combinations.

The GOG is currently comparing the two “winning combinations”, doxorubicin/ cisplatin + paclitaxel + GCSF and carboplatin-paclitaxel. As carboplatin-paclitaxel is a more convenient and less toxic regimen, it would be preferable if equally efficacious. It is likely that other platinum doublets are equally good. Platin/vinorelbine or carboplatin-pegylated liposomal doxorubicin have similar RRs to platin/taxane in phase II studies.

Chemotherapy, predominantly cisplatin–doxorubicin, has improved survival in 3 of the 4 phase III studies conducted, in comparison to irradiation.

Progression still was seen in up to 50% (dependant upon stage). Using “platin/ taxane” should improve this somewhat, but adding agents directed at molecular targets, e.g., EGFR, VEGF, AKt will be required.

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References

  1. FIGO. Annual report on the results of treatment in gynecologic cancers–vol 23. J Epidemiol Biostat 1998;3:335–61.

    Google Scholar 

  2. McCluggage WG. Uterine carcinosarcomas (malignant mixed Mullerian tumors) are meta-plastic carcinomas. Int J Gynecol Cancer 2002;12:687–90.

    Article  PubMed  CAS  Google Scholar 

  3. Fleming GF. Systemic chemotherapy for uterine carcinoma: metastatic and adjuvant. J Clin Oncol 2007;25:2983–90.

    Article  PubMed  CAS  Google Scholar 

  4. Elit L, Hirte H. Novel strategies for systemic treatment of endometrial cancer. Expert Opin Investig Drugs 2000;9: 2831–53.

    Article  PubMed  CAS  Google Scholar 

  5. Thigpen JT, Blessing JA, DiSaia PJ, Yordan E, Carson LF, Evers C. A randomized comparison of doxorubicin alone versus doxorubicin plus cyclophosphamide in the management of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 1994;12:1408–14.

    PubMed  CAS  Google Scholar 

  6. Aapro MS, van Wijk FH, Bolis G, et al. Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group. Ann Oncol 2003;14:441–8.

    Article  PubMed  CAS  Google Scholar 

  7. Thigpen JT, Brady MF, Homesley HD, et al. Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: a gynecologic oncology group study. J Clin Oncol 2004;22:3902–8.

    Article  PubMed  CAS  Google Scholar 

  8. Fleming GF, Brunetto VL, Cella 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.

    Article  PubMed  CAS  Google Scholar 

  9. Weber B, Mayer F, Bougnoux P, et al. What is the best chemotherapy regimen in recurrent or advanced endometrial carcinoma? Preliminary results. Proc Am Soc Clin Oncol 2003;22:453 (abstract).

    Google Scholar 

  10. Gallion HH, Brunetto VL, Cibull M, et al. Randomized phase III trial of standard timed doxorubicin plus cisplatin versus circadian timed doxorubicin plus cisplatin in stage III and IV or recurrent endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol 2003;21:3808–13.

    Article  PubMed  CAS  Google Scholar 

  11. Fleming GF, Filiaci VL, Bentley RC, et al. Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study. Ann Oncol 2004;15:1173–8.

    Article  PubMed  CAS  Google Scholar 

  12. Long HJ, Nelimark RA, Cha SS. Comparison of methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) vs doxorubicin and cisplatin (AC) in advanced endometrial carcinoma. Proc Am Soc Clin Oncol 1995;12:1408–14 (abstract).

    Google Scholar 

  13. Kristensen GB, Vergote I, Eisenhauer E, et al. First line treatment of ovarian/tubal/ peritoneal cancer FIGO stage II or without epirubicin (TEC vs. TC). A Gynecologic Cancer Intergroup and NCIC CTG. Results on progression free survival. Proc Am Soc Clin Oncol 2004;23:A5003 (abstract).

    Google Scholar 

  14. Hoskins PJ, Swenerton KD, Pike JA, et al. Paclitaxel and carboplatin, alone or with irradiation, in advanced or recurrent endometrial cancer: a phase II study. J Clin Oncol 2001;19: 4048–53.

    PubMed  CAS  Google Scholar 

  15. Le LH, Swenerton KD, Elit L, et al. Phase II multicenter open-label study of carboplatin and pegylated liposomal doxorubicin in uterine and cervical malignancies. Int J Gynecol Cancer 2005;15:799–806.

    Article  PubMed  CAS  Google Scholar 

  16. Pignata S, Scambia G, Savarese A, et al. Carboplatin plus paclitaxel versus carboplatin plus Stealth liposomal doxorubicin in patients with ovarian cancer (AOC): preliminary activity results o the MITO-2 randomized trial. Proc Am Soc Clin Oncol 2007;A5532 (abstract).

    Google Scholar 

  17. Hilpert F, Loibi S, Huober J, et al. Combination therapy with pegylated liposomal doxorubicin and carboplatin in malignant gynecologic tumors: a prospective multicenter phase II trial of the AGO-OVAR and the AGO Kommission Uterus (AGO-K-Ut). J Clin Oncol 2006;24:279s (abstract).

    Google Scholar 

  18. Gebbia V, Testa A, Borsellino N, Ferrera P, Tirrito M, Palmeri S. Cisplatin and vinorelbine in advanced and/or metastatic adenocarcinoma of the Endometrium: a new highly active chemo-therapeutic regimen. Ann Oncol 2001;12:767–72.

    Article  PubMed  CAS  Google Scholar 

  19. Santoro A. Carboplatin and vinorelbine combination for treatment of advanced endometrial cancer. Proc Am Soc Clin Oncol 1998;17:A1444 (abstract).

    Google Scholar 

  20. Hogberg T, Rosenberg P, Kristensen G, et al. A randomized phase III study on adjuvant treatment with radiation (RT) ± chemotherapy in early stage high risk endometrial cancer. Proc Am Soc Clin Oncol 2007:A5503.

    Google Scholar 

  21. Randall ME, Filiaci VL, Muss H, 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.

    Article  PubMed  CAS  Google Scholar 

  22. Maggi R, Lissoni A, Spina F, et al. Adjuvant chemotherapy vs. radiotherapy in high-risk endometrial carcinoma: results of a randomized trial. Br J Cancer 2006;95:266–71.

    Article  PubMed  CAS  Google Scholar 

  23. Susumu N, Sagae S, Udagawa Y, 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.

    Article  PubMed  CAS  Google Scholar 

  24. Wolfson AH, Brady MF, Rocereto T, et al. A gynecologic oncology group randomized phase III trial of whole abdominal irradiation (WAI) vs cisplatin–ifosfamide and mesna (CIM) as post-surgical therapy in stage I-IV carcinosarcoma (CS) of the uterus. Gynecol Oncol 2007;107:177–85.

    Article  PubMed  CAS  Google Scholar 

  25. Sutton G, Brunetto VL, Kilgore L, et al. A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: a Gynecologic Oncology Group Study. Gynecol Oncol 2000;79:147–53.

    Article  PubMed  CAS  Google Scholar 

  26. Homesley HD, Filiaci V, Markman M, et al. Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group Study. J Clin Oncol 2007; 25:526–31.

    Article  PubMed  CAS  Google Scholar 

  27. Hoskins PJ, Le N, Ellard S, et al. Carboplatin plus paclitaxel for advanced or recurrent uterine malignant mixed mullerian tumors. The British Columbia Cancer Agency experience. Gynecol Oncol 2008;108:58–62.

    Article  PubMed  CAS  Google Scholar 

  28. Gadducci A, Cosio S, Genazzani AR. Old and new perspectives in the pharmacological treatment of advanced or recurrent endometrial cancer: hormonal therapy, chemotherapy and molecularly targeted therapies. Crit Rev Oncol Hematol 2006;58:242–56.

    Article  PubMed  Google Scholar 

  29. Scudder SA, Liu P Y, Wilcynski SP, Smith HO, Jiang C, Hallum III AV, Smith GB, Hannigan E V, Markman M, Alberts DS. Paclitaxel and carboplatin with amifostine in advanced, recurrent, or refractory endometrial adenocarcinoma: a phase II study of SWOG. Gynecologic Oncology 2005;96:610–615.

    Article  PubMed  CAS  Google Scholar 

  30. Sovak MA, Dupont J, Hensley ML, et al. Paclitaxel and carboplatin in the treatment of advanced or recurrent endometrial cancer: a large retrospective study. Int J Gynecol Cancer 2007;17:197–203.

    Article  PubMed  CAS  Google Scholar 

  31. Akram T, Maseelall P, Fanning J. Carboplatin and paclitaxel for the treatment of advanced or recurrent endometrial cancer. Am J Obstet Gynecol 2005;192:1365–1367.

    Article  PubMed  CAS  Google Scholar 

  32. Price F V, Edwards RP, Kelley JL et al. A trail of outpatient paclitaxel and carboplatin to advanced, recurrent, and histologic high risk endometrial carinoma: a preliminary report. Seminars in Oncology 1997;24:S15-78–S15-82.

    Google Scholar 

  33. Nakamura T, Onishi Y, Yamamoto F, et al. Evaluation of paclitaxel and carboplatin in patients with endometrial cancer. Gan To Kagaku Ryoho 2000;27:257–262.

    PubMed  CAS  Google Scholar 

  34. Trudeau M, Stanmir G, Langleben G, Letendre E, Gagne G. Paclitaxel and cisplatin: an active regimen in metastatic cancer of the endometrium. Int J Gynecol Cancer 1999;9(suppl 1):69.

    Google Scholar 

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Hoskins, P.J. (2009). The Role of Platins in Newly Diagnosed Endometrial Cancer. In: Bonetti, A., Leone, R., Muggia, F.M., Howell, S.B. (eds) Platinum and Other Heavy Metal Compounds in Cancer Chemotherapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-459-3_34

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