The role of hormonal therapy in patients with uterine carcinoma

Česká verzia

Authors: P. Vinklerová ¹ ; Luboš Minář ¹ ; Michal Felsinger ¹ ; Matěj Anton ¹ ; P. Ventruba ¹; Markéta Bednaříková ² ; J. Hausnerová ³; E. Jandáková ³; M. Číhalová ³; Vít Weinberger ¹
Authors place of work: Gynekologicko-porodnická klinika LF MU a FN, Brno, npřednosta prof. MUDr. P. Ventruba, DrSc., MBA ¹; Interní hematologická a onkologická klinika LF MU a FN, Brno, přednosta prof. MUDr. J. Mayer, CSc. ²; Ústav patologie LF MU a FN, Brno, přednosta doc. MUDr. L. Křen, Ph. D. ³
Published in the journal: Ceska Gynekol 2018; 83(4): 263-270
Category:

Summary

Objective: The aim of the study was to describe the role of hormonal therapy in the treatment of malignant uterine tumors, indications, the effect of the treatment and to verify its safety in our study cohort. We also present an overview of recent studies on that topic.

Design: Unicentric retrospective observational study and review of recent literature.

Setting: Department of Obstetrics and Gynecology, Masaryk University, University Hospital Brno.

Methods: The results of recent relevant studies and reviews published in English until December 2017 were used for the review. The publications were searched using the PubMed server. All patients diagnosed in our oncogynecological center between 2010 and 2016 and who were treated hormonally – either in primary therapy or in relapse settings, were included in our study. We were interested in age, BMI, stage of disease, histological type and grade of tumor, occurrence of adverse effects, duration of survival, reasons for choosing hormonal therapy. Medroxyprogesterone-acetate or megestrol-acetate was used in the treatment.

Results: Between 2010 and 2016, 415 malignant tumors of the uterus were diagnosed in our oncology center. Recurrence of the disease occurred in 31 patients (8%), on average 16 months after primary treatment. Primary hormonal therapy was used in only 19 patients (5%), mostly because of contraindications of another treatment due to high age, comorbidities or obesity. Median age of patients was 83 years, mean BMI 41, median survival of patients who died was 8 months. Five patients (16%) were treated hormonally for the recurrence. Median survival from diagnosis of recurrence was 20 months. One patient (4%) experienced partial pulmonary embolism.

Conclusion: Hormonal therapy plays an irreplaceable role in uterine cancer patients, especially in primary non-operable patients, in treatment of a relapse, or in a fertility-sparing procedure. This treatment option is safe, with minimal adverse effects.

Keywords: endometrial carcinoma, hormone therapy, medroxyprogesterone-acetate, megestrol-acetate, palliative therapy, fertility-sparing treatment

Zdroje

1.   Amant, F., Mirza, MR., Koskas, M., Creutzberg, CL. Cancer of the corpus uteri. In J Gynaecol Obstet, 2015, 131, 2, p. 96–104.
2.   Baker, WD., Pierce, SR., Mills, AM., et al. Nonoperative management of atypical endometrial hyperplasia and grade 1 endometrial cancer with the levonorgestrel intrauterine device in medically ill post-menopausal women. Gynecol Oncol, 2017, 146, 1, p. 34–38.
3.   Colombo, N., Creutzberg, C., Amant, F., et al. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: diagnosis, treatment and follow-up. Ann Oncol, 2016, 27, p. 16–41.
4.   Creasman, WT., Odicino, F., Maisonneuve, P., et al. Carcinoma of the corpus uteri. FIGO 6th annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet, 2006, 95, p. 105–143.
5.   Decruze, SB., Green, JA. Hormone therapy in advanced and recurrent endometrial cancer: a systematic review. Int J Gynecol Cancer, 2007, 17, p. 964–978.
6.   Dursun, P., Erkanli, S., Güzel, AB., et at. A Turkish Gynecologic Oncology Group study of fertility-sparing treatment for early-stage endometrial cancer. Int J Gynaecol Obstet, 2012, 119, 3, p. 270–273.
7.   Dušek, L., Mužík, J., Kubásek, M., et al. Epidemiologie zhoubných nádorů v České republice [online]. http://www.svod.cz. [cit. 2018-02-01].
8.   Emons, G., Gunthert, A., Thiel, FC., et al. Phase II study of fulvestrant 250 mg/month in patients with recurrent or metastatic endometrial cancer: a study of the Arbeitsgemeinschaft Gynakologische Onkologie. Gynecol Oncol, 2013, 129, p. 495–499.
9.   Ethier, JL., Desautels, DN., Amir, E., MacKay, H. Is hormonal therapy effective in advanced endometrial cancer? A systematic review and meta-analysis. Gynecol Oncol, 2017, 147, 1, p. 158–166.
10.   Erkanli, S., Ayhan, A. Fertility-sparing therapy in young women with endometrial cancer: 2010 update. Int J Gynecol Cancer, 2010, 20, p. 1170–1187.
11.   Felsinger, M., Minář, L., Weinberger, V., Hudeček, R. Radikální fertilitu zachovávající operační výkony u gynekologických maginit – pětiletý soubor. Čes Gynek, 2015, 80, 5, s. 339–344.
12.   Fiorica, JV., Brunetto, VL., Hanjani, P., et al. Phase II trial of alternating courses of megestrol acetate and tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol, 2004, 92, 1, p. 10–14.
13.   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, 11, p. 2159–2166.
14.   Frühauf, F., Dvořák, M., Haaková, L., et al. Ultrazvukový staging karcinomu endometria – doporučená metodika vyšetření. Čes Gynek, 2014, 79, 6, s. 466–476.
15.   Gunderson, CC., Fader, AN., Carson, KA., et al. Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma: A systematic review. Gynecol Oncol, 2012, 125, p. 477–482.
16.   Chen, M., Jin, Y., Li, Y., et al. Oncologic and reproductive outcomes after fertility-sparing management with oral progestin for women with complex endometrial hyperplasia and endometrial cancer. Int J Gynaecol Obstet, 2016, 132, 1, p. 34–38.
17.   Chiva, L., Lapuente, F., González-Cortijo, L., et al. Sparing fertility in young patients with endometrial cancer. Gynecol Oncol, 2008, 111, p. 101–104.
18.   Karagol, H., Saip, P., Uygun, K., et al. Evaluation of prognostic factors and comparison of systemic treatment modalities in patients with recurrent or metastatic endometrial carcinoma. Med Oncol, 2006, 23, 4, p. 543–548.
19.   Kim, MK., Seong, SJ. Conservative treatment for atypical endometrial hyperplasia: What is the most effective therapeutic method? J Gynecol Oncol, 2014, 25, p. 164–165.
20.   Kim, MK., Seong, SJ., Song, T., et al. Comparison of dilatation & curettage and endometrial aspiration biopsy accuracy in patients treated with high-dose oral progestin plus levonorgestrel intrauterine system for early-stage endometrial cancer. Gynecol Oncol, 2013, 130, p. 470–473.
21.   Kitchener, H., Swart, AM., Qian, Q., et al. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomized study. Lancet, 2009, 373, 9658, p. 125–136.
22.   Lee, NK., Cheung, MK., Shin, JY., et al. Prognostic factors for uterine cancer in reproductive-aged women. Obstet Gynecol, 2007, 109, p. 655–662.
23.   Lindemann, K., Malander, S., Christensen, RD., et al. Examestane in advanced or recurrent endometrial carcionoma: prospective phase II study by the Nordic Society of Gynecologic Oncology (NSGO). BMC Cancer, 2014, 5, 14, p. 68.
24.   Ma, BB., Oza, A., Eisenhauer, E., et al. The activity of letrozole in patients with advanced or recurrent endometrial cancer and correlation with biological markers – a study of the National Cancer Institute of Canada Clinical Trials Group. Int J Gynecol Cancer, 2004, 14, p. 650–658.
25.   Moore, TD., Phillips, PH., Nerenstone, SR., Cheson, BD. Systemic treatment of advanced and recurrent endometrial carcinoma: current status and future directions. J Clin Oncol, 1991, 9, 6, p. 1071–1088.
26.   Park, JY., Kim, DY., Kim, JH., et al. Long-term oncologic outcomes after fertility-sparing management using oral progestin for young women with endometrial cancer (KGOG 2002). Eur J Cancer, 2013, 49, p. 868–874.
27.   Park, JY., Kim, DY., Kim, TJ., et al. Hormonal therapy for women with stage IA endometrial cancer of all grades. Obstet Gynecol, 2013, 122, p. 7–14.
28.   Park, JY., Lee, SH., Seong, SJ., et al. Progestin retreatment in patients with recurrent endometrial adenocarcinoma after successful fertility-sparing management using progestin. Gynecol Oncol, 2013, 129, p. 7–11.
29.   Pronin, SM., Novikova, OV., Andreeva, JY., et al. Fertility-sparing treatment of early endometrial cancer and complex atypical hyperplasia in young women of childbearing potential. Int J Gynecol Cancer, 2015, 25, p. 1010–1014.
30.   Rodolakis, A., Biliatis, I., Morice, P., et al. European Society of Gynecological Oncology Task Force for Fertility Preservation: clinical recommendations for fertility-sparing management in young endometrial cancer patients. Int J Gynecol Cancer, 2015, 25, p. 1258–1265.
31.   Rose, PG., Brunetto, VL., VanLe, L., et al. A phase II trial of anastrozole in advanced recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol, 2000, 78, p. 212–216.
32.   Tangen, IL., Onyango, TB., Kopperud, R., et al. Androgen receptor as potential therapeutic target in metastatic endometrial cancer. Oncotarget, 2016, 7, 31, p. 49289–49298.
33.   Tangen, IL., Werner, HM., Berg, A., et al. Loss of progesterone receptor links to high proliferation and increases from primary to metastatic endometrial cancer lesions. Eur J Cancer, 2014, 50, p. 3003–3010.
34.   Thigpen, JT., Brady, MF., Alvarez, RD., et al. Oral medroxyprgesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. J Clin Oncol, 1999, 17, 6, p. 1736–1744.
35.   Thigpen, JT., Brady, MF., Homesley, HD., et al. Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol, 2001, 15, 19, p. 364–367.
36.   van der Putten, LJM., van Weelden, WJ., de Inda, MA., et al. Estrogen receptor pathway activity in endometrial carcinomas and its relation to tumor grade and recurrence. Abstract submitted to AACR, manuscript in progress.
37.   Verhaegh, W., van Ooijen, H., Inda, MA., et al. Selection of personalized patient therapy through the use of knowledge-based computational models that identify tumor-driving signal transduction pathways. Cancer Res, 2014, 74, 11, p. 2936–2945.
38.   Wang, CB., Wang, CJ., Huang, HJ., et al. Fertility preserving treatment in young patients with endometrial adenocarcinoma. Cancer, 2002, 94, p. 2192–2198.