Multicenter Phase II Study of Fertility-Sparing Treatment With Medroxyprogesterone Acetate for Endometrial Carcinoma and Atypical Hyperplasia in Young Women

Ushijima, Kimio; Yahata, Hideaki; Yoshikawa, Hiroyuki; Konishi, Ikuo; Yasugi, Toshiharu; Saito, Toshiaki; Nakanishi, Tōru; Sasaki, Hiroshi; Saji, Fumitaka; Iwasaka, Tsuyoshi; Hatae, Masayuki; Kudoh, Shoji; Saito, Tsuyoshi; Terakawa, Naoki; Yaegashi, Nobuo; Hiura, Masamichi; Sakamoto, Atsuhiko; Tsuda, Hitoshi; Fukunaga, Masao; Kamura, Toshiharu

doi:10.1200/jco.2006.08.8344

Cited by 363 publications

(297 citation statements)

References 18 publications

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“…Studies at various institutions have reported the results of fertility-sparing treatment for EC using progesterone preparations (8)(9)(10)(11)(12)(13)(14)(15)(16)(17). However, as the number of cases have been low, the efficacy of such treatment has yet to be clarified.…”

Section: Introductionmentioning

confidence: 99%

Fertility-sparing treatment using medroxyprogesterone acetate for endometrial carcinoma

et al. 2012

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Abstract. The purpose of this study was to present the results of fertility-sparing treatment using medroxyprogesterone acetate (MPA) for endometrial carcinoma (EC), and to clarify patient characteristics by investigating patient background factors. A total of 59 patients with EC, who received MPA as fertility-sparing therapy at two institutions over a 21-year period between 1987 and 2008, were studied retrospectively. Patients were administered oral MPA at 400-600 mg/day for 16-24 weeks as long as they responded. Endometrial tissue was assessed twice, at 8-12 weeks (during treatment) and shortly after treatment. The overall complete response (CR) rate was 71%. A total of 22 (52%) of 42 responders later developed relapse. A total of 19 cases became pregnant, and 25 infants were born. Eighty percent of recurrences occurred within 2 years. For stages Ⅰa and Ⅰb-Ⅱa (FIGO, 1988), initial CR rates were 80.0 and 42.9%, respectively (p<0.01), demonstrating a significant difference. Total hysterectomy was performed for 26 patients (44%) due to recurrence or failure to respond to the initial treatment. Among these 26 patients, postoperative stages were more advanced in 10 patients (38%). The grade advanced (became more poorly differentiated) postoperatively in 2 patients (8%). Premenopausal females with EC can be treated successfully with MPA, however patients should be informed of the risks and limitations of this conservative treatment. IntroductionIn Western countries, endometrial carcinoma (EC) is the most common type of malignant tumor in the field of gynecology (1,2). A state of persistent high estrogen, as observed with ovulation disorders and obesity, is considered a risk factor (3-5). The standard treatments for EC are total hysterectomy and bilateral adnexectomy.EC is a disease that frequently affects perimenopausal females, however approximately 10% of affected females are ≤40 years old, and the incidence in young females has recently been on the increase (6). As in Western countries, the number of ≤40-year-old females with EC in Japan is on the rise (7). Thus, the number of patients who select to undergo fertilitysparing treatment is growing.Studies at various institutions have reported the results of fertility-sparing treatment for EC using progesterone preparations (8-17). However, as the number of cases have been low, the efficacy of such treatment has yet to be clarified. Furthermore, few studies have closely described the clinical background of young females with early-stage EC wishing to undergo fertility-sparing treatment.The present study investigated the effects of treatment, prognosis, pregnancy status and other factors, in order to demonstrate the therapeutic outcomes of current fertility-sparing treatment. Furthermore, patient background factors were investigated to elucidate the characteristics of the patient group. Patients and methods Patients.A total of 59 patients with EC who underwent fertilitysparing treatment, at either the Jichi Medical University Hospital or the Kitasato University Hospit...

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Section: Introductionmentioning

confidence: 99%

Fertility-sparing treatment using medroxyprogesterone acetate for endometrial carcinoma

et al. 2012

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“…Cases in which extrauterine metastasis occurred during conservative therapy, such as those reported by Imai et al and Ota et al, were also excluded because such cases can be treated by standard surgery. Thus, 13 cases of extrauterine recurrence after temporary remission are listed in Table 2 [3,[8][9][10][11][12][13][14]. Six of these cases had ovarian lesions as the extrauterine site.…”

Section: Discussionmentioning

confidence: 99%

“…This therapy is indicated for patients with grade 1 endometrioid histology and very early stage cancer. Good hormonal response rates between 57% and 75% have been achieved, but the relapse rates after remission are also high, varying between 47% in follow-up of 7 to 22 months and 89% after follow-up of over 30 months [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Relapse as Advanced Carcinosarcoma Following Uterus-Preserving Therapy in a Patient with Early-Staged and Grade 1 Endometrioid Adenocarcinoma: A Case Report and Review of the Literature

Takeshita¹

2014

Gynecol Obstet (sunnyvale)

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Fertility-sparing treatment with high-dose progestin is now used in many young patients with early stage, grade 1 endometrioid adenocarcinoma. The response rate of this therapy is quite good, but the relapse rate is relatively high. If the site of recurrence is limited to the uterus, this may be treated with additional hormone therapy or hysterectomy. We recently experienced a case of a 30-year-old primigravida patient in whom intraperitoneal dissemination of carcinosarcoma occurred during follow-up after apparent complete remission of early-stage grade 1 endometrioid adenocarcinoma. We report the case as an example of a rare high-grade histology tumor that relapsed in an extrauterine site after primary remission had been achieved with high-dose progestin therapy. In a review of the literature through a MEDLINE search, we found 13 articles describing relapse in an extrauterine site, including 6 ovarian metastases, 4 retroperitoneal lymph node metastases, and 3 metastases to organs other than the ovary. Early stage, well-differentiated endometrioid adenocarcinoma of the uterine corpus is generally considered to have a good prognosis, but counseling of patients regarding life decisions is important, with provision of sufficient information on the possibility of extrauterine progression or disseminated recurrence.

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“…To summarize the domestic and overseas reports on progestin therapy applied as fertility-preserving therapy in 1997 through 2008, the lesions disappeared in 164 (75%) of the 218 cases of endometrial cancer (corresponding to G1 endometrioid adenocarcinoma, FIGO 1988 surgical stage Ia) in response to progestin therapy. Among these 164 cases showing disappearance of lesions, recurrence was later noted in 53 (36%) of the 148 cases where information on the presence/absence of recurrence was available (Table I) (14,(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). When progestin therapy was applied to 47 cases of atypical endometrial hyperplasia, 42 cases (89%) showed disappearance of lesions, and 8 (19%) of these 42 cases later showed recurrence (Table II) (26,27,31,35).…”

Section: Progestin Therapy For Endometrial Cancermentioning

confidence: 99%

“…Among these 164 cases showing disappearance of lesions, recurrence was later noted in 53 (36%) of the 148 cases where information on the presence/absence of recurrence was available (Table I) (14,(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). When progestin therapy was applied to 47 cases of atypical endometrial hyperplasia, 42 cases (89%) showed disappearance of lesions, and 8 (19%) of these 42 cases later showed recurrence (Table II) (26,27,31,35). Regarding the efficacy of progestin therapy on endometrial cancer, Montz et al reported that when progestin therapy was administered to cases of G1 endometrial cancer (FIGO 1988 surgical stage Ia) not indicated for surgery for reasons of influence of complications or preservation of fertility, the tumor was histologically rated as negative in 7 of the 11 cases at 6 months and 6 of the 8 cases at 12 months after the start of treatment (36).…”

Section: Progestin Therapy For Endometrial Cancermentioning

confidence: 99%

Progestin therapy for endometrial cancer: The potential of fourth-generation progestin (Review)

et al. 2012

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Abstract. Progestin preparations are made of synthetic progesterone and have often been used for hormone therapy in gynecological patients with endometriosis or endometrial cancer. Hormone therapy using progestin is considered to be one of the effective means of treatment particularly when dealing with endometrial cancer (an estrogen-dependent tumor). Numerous reports have been published concerning its efficacy in advanced or recurrent cases of atypical endometrial hyperplasia or endometrial cancer. Dienogest has been developed as a fourth-generation progestin for hormone therapy for endometriosis that can be used with high safety for long periods of time. In Japan, dienogest has been recommended as a first-line drug for endometriosis-associated pain. However, its antitumor activity has also been attracting close attention following a report that this drug suppressed the proliferation in vitro of endometrial cancer-derived cell lines which failed to respond to other progestins such as medroxyprogesterine acetate (MPA). The mechanism for antitumor activity of dienogest is considered to differ from the mechanism for antitumor activity of conventional progestin preparations used for treatment of endometrial cancer. This drug is expected to be clinically applicable as a new drug for the treatment of endometrial cancer. Contents

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Multicenter Phase II Study of Fertility-Sparing Treatment With Medroxyprogesterone Acetate for Endometrial Carcinoma and Atypical Hyperplasia in Young Women

Abstract: The efficacy of fertility-sparing treatment with a high-dose of MPA for EC and AH was proven by this prospective trial. Even in responders, however, close follow-up is required because of the substantial rate of recurrence.

Cited by 363 publications

References 18 publications

Fertility-sparing treatment using medroxyprogesterone acetate for endometrial carcinoma

Fertility-sparing treatment using medroxyprogesterone acetate for endometrial carcinoma

Relapse as Advanced Carcinosarcoma Following Uterus-Preserving Therapy in a Patient with Early-Staged and Grade 1 Endometrioid Adenocarcinoma: A Case Report and Review of the Literature

Progestin therapy for endometrial cancer: The potential of fourth-generation progestin (Review)

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