In the study of 34 women, almost all of the patients with atypical endometrial hyperplasia (AEH) were cured by a year's exposure to the implantable intrauterine device (IUD) along with six months of gonadotropin-releasing hormone therapy, reported Lucas Minig, MD, of the Hospital Universitario Madrid Sanchinarro in Madrid, and colleagues. Minig was formerly at the European Institute of Oncology in Milan, Italy, where the study was carried out.
As well, 57.1% of women with well-differentiated endometrial cancer limited to the endometrium had a complete response to the therapy, Minig and co-authors wrote online in Annals of Oncology .The finding offers the possibility of therapy that would allow many women to avoid a hysterectomy and have children.
Indeed, the researchers reported, of 27 women who had a complete response to the treatment, nine went on to have a total of 11 spontaneous pregnancies.
For women, the researchers noted, endometrial cancer is the sixth most common cancer worldwide, with nearly 290,00 cases in 2008 and nearly 75,000 deaths.
The usual therapy is hysterectomy, although some patients have been treated with systemic hormone therapy, which has a set of adverse reactions including rashes, headaches, and abnormal uterine bleeding.
The advantage of the IUD approach, Minig said in a statement, is that it "allows us to deliver a much higher dose of the hormone levonorgestrel to the endometrial surface than would be possible via a pill."
Because blood concentrations remain low, many of the side effects can be avoided, he added.
"Progestin acts directly on endometrial cancer by inducing endometrial epithelial apoptosis and indirectly on withdrawal by physical shedding of tumor tissue," the researchers explained in their discussion. "There is some evidence that interrupted, rather than continuous, progestin therapy may have added benefit."
To test the idea of using progestin therapy via an IUD, they analyzed results from 34 patients, ages 20 through 40 (including 20 with AEH and 14 with carcinoma) who had the device implanted for a year. Depot injections of gonadotropin-releasing hormone were given monthly for the first six months.
Of the 20 patients with AEH, Minig and colleagues reported, 19 -- or 95% -- had a complete response to the treatment at the end of the year, although four had later relapses and required further therapy.Of the 14 patients with early stage endometrial cancer, eight -- or 57.1% -- had a complete response, two had stable disease, and the cancers progressed in four.
Relapses or recurrences were treated either with the IUD approach or by hysterectomy and all the women survived with no evidence of disease at their last follow-up (mean 29 months), Minig and colleagues reported.
"The response rate we achieved in this trial was in the same range as other methods of conservatively treating endometrial cancer," Minig said. "We think that treatment with levonorgestrel-releasing IUDs is ideally suited to young patients who may not want to have children immediately but would like to have the opportunity to have them in the future."
The researchers said the key to successful treatment is careful selection and evaluation of the patients.
"Patient qualification to exclude preexisting myoinvasive or distant disease is a crucial, although imperfect, prerequisite. 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," Minig and co-authors wrote. "Close follow-up during and after treatment to monitor failures is crucial for timely triage into alternative, usually surgical, therapies."
A key limitation to the study was its small sample size.
