Case ReportAnastrozole therapy in recurrent ovarian adult granulosa cell tumors: A report of 2 cases
Introduction
Sex cord stromal tumors account for approximately 6 to 7% of all ovarian tumors and adult granulosa cell tumors represent about 70–85% of the stromal tumors [1], [2]. Granulosa cell cancers are typically indolent tumors with a 10-year survival of 85 to 95%. These tumors may be hormonally active and patients often present with symptoms of either estrogen or androgen excess. Granulosa cell tumors are also known for the production of excess estrogen, follicle regulating protein, folliculin, and inhibin [2]. Inhibin is a glycoprotein hormone that is composed of one alpha and two beta subunits; elevations of inhibin are frequently found in ovarian cancer, most notably granulosa cell tumors and mucinous epithelial tumors [3], [4]. Of note, normal postmenopausal women have undetectable inhibin levels [5]. Inhibin has been evaluated as a potential biomarker for this disease as levels of inhibin can be increased up to seven fold pre-operatively in patients with granulosa cell tumors and inhibin B levels may be more accurate than inhibin A levels [6], [7]. Inhibin levels can also be monitored over time after surgery and may be elevated prior to clinical evidence of recurrence [1], [2], [6], [8].
Initial treatment includes surgery for removal and staging of the granulosa cell tumor. Over 90% of adult granulosa tumors are stage I at the time of surgery [1]; thus, many patients can be treated initially with surgery alone. Though no standard chemotherapy regimen exists for advanced or recurrent tumors, various chemotherapy regimens have been reported with variable response rates [2], [9], [10], [11], [12], [13]. The most promising regimens for advanced stage disease appear to be platinum-based therapies, with the combination of bleomycin, cisplatin, and etoposide (BEP) showing both effectiveness and manageable toxicity and this has been largely adopted as the standard of care [11]. More recently, there has been increasing data on the potential effectiveness of paclitaxel and carboplatin [9], [10].
As these are hormonally active tumors, there is interest in evaluating hormonal manipulation as a potential treatment regimen. GnRH agonists and other hormonally active agents have previously been shown to be moderately active in treating both epithelial [14] and stromal ovarian tumors yet definitive data are lacking [15], [16], [17], [18], [19]. Anastrozole, is an aromatase inhibitor that is given orally in a once a day dosing. Aromatase inhibitors work by inhibiting the conversion of androstendione to estrone [20]. It is a well tolerated drug that has begun to supplant tamoxifen in the adjuvant setting for women with estrogen receptor positive breast cancer and as a first line agent in receptor positive tumors [20]. Here, we present two cases in which anastrozole (Arimidex®) has been successfully used to treat recurrent disease in women with adult granulosa cell tumors who had received multiple other treatment modalities.
Section snippets
Case 1
PB was a 48-year-old female who previously underwent hysterectomy for a benign indication. In May 1999, she underwent bilateral salpingo-oophorectomy and staging for chronic pelvic pain. At that time the left ovary was found to be grossly abnormal, and the pathology revealed a stage IC adult granulosa cell tumor. The patient was treated with surgery alone for this initial tumor and was followed clinically for 2 years before being lost to follow-up. In January 2003, she had increasing pain, and
Discussion
Standard treatment of stromal cell ovarian malignancies consists of surgical staging/debulking followed by platinum-based chemotherapy for advanced stage disease. Most women will be cured by this therapy, but the recommended chemotherapy regimen for adjuvant treatment and recurrence remain debated. For years, BEP has been the accepted regimen with 33% complete response and 50% partial response rates, however; durable remission was seen in less than half of these patients [2]. Emerging data show
Acknowledgment
Supported in part by a Building Interdisciplinary Research Careers in Women's Health (BIRCWH) Grant: NIDA 2K12DA14040-06.
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2018, Gynecologic Oncology ReportsCitation Excerpt :Freeman reported two cases of recurrent ovarian GCT treated with anastrozole. In both cases, after debulking and initiation of anastrozole, inhibin levels normalized (Freeman and Modesitt, 2006). While our patient's inhibin levels never fully normalized she returned to levels in the 200 s–300 s and has remained thus for 4 years.
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2017, Critical Reviews in Oncology/HematologyCitation Excerpt :This was the case of a patient with recurrent oestrogen receptor negative and progesterone receptor positive GrCT who achieved an impressive complete response of 22 months and a DFS of 5 years with the alternative treatment of biweekly cycles of megestrol and tamoxifen (Hardy et al., 2005). The use of anastrozole and letrozole in recurrent GrCT resulted in remissions ranging from 12 to 54 months (Freeman and Modesitt, 2006; Abdul Munem et al., 2012; Korach et al., 2009; Alhilli et al., 2012). The role of anastrozole in GrCT is being evaluated in the international multicenter phase II PARAGON trial, run by the Australia New Zealand Gynaecological Oncology Group.
Retreatment with aromatase inhibitor therapy in the management of granulosa cell tumor
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