A uterus-sparing therapy that combines delivery of progesterone via an intrauterine device with injections of gonadotropin-releasing hormone appears to have preserved fertility in a majority of women treated for early endometrial cancer in a small prospective study.
Data on 34 patients younger than 43 years were published online Sept. 28 in the Annals of Oncology.
Previous studies had examined oral progestins as fertility-preserving therapies for younger women with atypical endometrial hyperplasia (AEH) and endometrial cancer, but neither the dose nor the schedule were standardized, said Dr. Lucas Minig of Hospital Universitario Madrid Norte Sanchinarro in Madrid, Spain, and coauthors.
In this study, Dr. Minig and colleagues tested the combination of a levonorgestrel-release intrauterine device (Mirena) and a gonadotropin-releasing hormone (GnRH) analog as a fertility-preserving treatment for AEH and well-differentiated endometrial cancer (EC-G1). “The progesterone-releasing intrauterine device (IUD) is a newly available delivery system for treatment of estrogen-dependent endometrial cancer,” the researchers said.
A total of 43 patients were selected between January 1996 and June 2009. Three patients dropped out, and five remain under treatment, leaving 20 women with AEH and 14 with EC-G1 in the current analysis. They received 20 mcg of levonorgestrel released daily by the IUD for up to 5 years and monthly depot injections of 3.75 mg of the GnRH for 6 months. The IUDs were removed after 1 year.
After 1 year of treatment, the complete response rate was 95% in the AEH patients and 57% in the EC-G1 patients, with 19 of 20 patients and 8 of 14 patients, respectively, responding in each group. Disease progression was noted in one AEH patient (5%) and four EC-G1 patients (28%).
Recurrence of disease occurred in 4 AEH patients and 2 EC-GI patients after an average of 36 months. They were staged surgically and received adjuvant chemotherapy and/or radiation. With the exception of one patient lost to follow-up, all were alive and disease free at last follow-up.
The researchers noted no major side effects or complications caused by the IUD-delivered hormonal treatment.
Of the 27 patients who had a complete response, 9 achieved 11 spontaneous pregnancies after their IUDs were removed. Seven of these had reached full term at the time of the report, and two ended in miscarriages.
The average age of the women was 34 years, and the median follow-up time was 29 months. Prior to the study, five women (14%) were diagnosed with concomitant early-stage ovarian cancer, but none of these patients underwent adjuvant chemotherapy, and two of them had full-term pregnancies (Ann. Onc. 2010 Sept. 28 [doi:10.1093/annonc/mdq463]).
The study was limited by its small size, but the trial is the first known to test the combination of IUD and GnRH in women with endometrial cancer who want to preserve fertility, the researchers noted. Longer follow-up data are needed to reinforce the findings, but the results suggest that the treatment can be effective in some patients. However, “given the risks of disease progression or relapse, only those patients with significant expected benefit from uterine retention should be considered and then only following an adequate pretreatment evaluation,” the researchers said.
Disclosures: The researchers said they had no financial conflicts to disclose.