Multicenter phase II study of fertility-sparing treatment with medroxyprogesterone acetate for endometrial carcinoma and atypical hyperplasia in young women.
OBJECTIVE
To assess the efficacy of fertility-sparing treatment using medroxyprogesterone acetate (MPA) for endometrial carcinoma (EC) and atypical endometrial hyperplasia (AH) in young women.


METHODS
This multicenter prospective study was carried out at 16 institutions in Japan. Twenty-eight patients having EC at presumed stage IA and 17 patients with AH at younger than 40 years of age were enrolled. All patients were given a daily oral dose of 600 mg of MPA with low-dose aspirin. This treatment continued for 26 weeks, as long as the patients responded. Histologic change of endometrial tissue was assessed at 8 and 16 weeks of treatment. Either estrogen-progestin therapy or fertility treatment was provided for the responders after MPA therapy. The primary end point was a pathologic complete response (CR) rate. Toxicity, pregnancy rate, and progression-free interval were secondary end points.


RESULTS
CR was found in 55% of EC cases and 82% of AH cases. The overall CR rate was 67%. Neither therapeutic death nor irreversible toxicities were observed; however, two patients had grade 3 body weight gain, and one patient had grade 3 liver dysfunction. During the 3-year follow-up period, 12 pregnancies and seven normal deliveries were achieved after MPA therapy. Fourteen recurrences were found in 30 patients (47%) between 7 and 36 months.


CONCLUSIONS
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.
Ushijima
Kimio
K
Japan Gynecologic Cancer Study Group, Tokyo, Japan. kimi@med.kurume-u.ac.jp
Yahata
Hideaki
H
Yoshikawa
Hiroyuki
H
Konishi
Ikuo
I
Yasugi
Toshiharu
T
Saito
Toshiaki
T
Nakanishi
Toru
T
Sasaki
Hiroshi
H
Saji
Fumitaka
F
Iwasaka
Tsuyoshi
T
Hatae
Masayuki
M
Kodama
Shoji
S
Saito
Tsuyoshi
T
Terakawa
Naoki
N
Yaegashi
Nobuo
N
Hiura
Masamichi
M
Sakamoto
Atsuhiko
A
Tsuda
Hitoshi
H
Fukunaga
Masaharu
M
Kamura
Toshiharu
T
D000328:Adult; D001241:Aspirin / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy*; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000188:drug therapy*; D004717:Endometrium / Q000473:pathology*; D005260:Female; D005298:Fertility / Q000187:drug effects*; D006801:Humans; D006965:Hyperplasia / Q000188:drug therapy*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011446:Prospective Studies; D016896:Treatment Outcome; D014591:Uterine Diseases / Q000188:drug therapy*
D017258:Medroxyprogesterone Acetate; D001241:Aspirin