Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, Morsani College of Medicine, University of South Florida; Tampa, FL; Department of Gynecologic Oncology, H. Lee Moffitt Cancer Center and Research Institute; Tampa, FL.
Am J Obstet Gynecol. 2023 Jun;228(6):724.e1-724.e9. doi: 10.1016/j.ajog.2023.02.029. Epub 2023 Mar 11.
The optimal treatment of recurrent ovarian granulosa cell tumors is not known. Preclinical studies and small case series have suggested direct antitumor activity of gonadotropin-releasing hormone agonists in the treatment of this disease, but little is known about the efficacy and safety of this approach.
This study aimed to describe patterns of use and clinical outcomes of leuprolide acetate in a cohort of patients with recurrent granulosa cell tumors.
This was a retrospective cohort study of patients enrolled in the Rare Gynecologic Malignancy Registry at a large cancer referral center and affiliated county hospital. Patients meeting inclusion criteria had a diagnosis of recurrent granulosa cell tumor and received either leuprolide acetate or traditional chemotherapy as cancer treatment. Outcomes were separately examined for leuprolide acetate used as adjuvant treatment, maintenance therapy, and the treatment of gross disease. Demographic and clinical data were summarized using descriptive statistics. Progression-free survival was calculated from the initiation of treatment to the date of disease progression or death, and compared between groups with the log-rank test. The 6-month clinical benefit rate was defined as the percentage of patients without disease progression 6 months after starting therapy.
Sixty-two patients received a total of 78 leuprolide acetate-containing therapy courses, owing to 16 instances of retreatment. Of these 78 courses, 57 (73%) were for treatment of gross disease, 10 (13%) were adjuvant to tumor reductive surgery, and 11 (14%) were for maintenance therapy. Patients had received a median of 2 (interquartile range, 1-3) systemic therapy regimens before their first leuprolide acetate treatment. Tumor reductive surgery (100% [62/62]) and platinum-based chemotherapy (81% [50/62]) were common before first leuprolide acetate exposure. The median duration of leuprolide acetate therapy was 9.6 months (interquartile range, 4.8-16.5). Nearly half of the therapy courses were single-agent leuprolide acetate (49% [38/78]). Combination regimens most often included an aromatase inhibitor (23% [18/78]). Disease progression was the most common cause of discontinuation (77% [60/78]); only 1 patient (1%) discontinued leuprolide acetate because of adverse events. In the treatment of gross disease, the 6-month clinical benefit rate for first use of leuprolide acetate was 66% (95% confidence interval, 54-82). Median progression-free survival was not statistically different compared with that which followed chemotherapy (10.3 months [95% confidence interval, 8.0-16.0] vs 8.0 months [95% confidence interval, 5.0-15.3]; P=.3).
In a large cohort of patients with recurrent granulosa cell tumors, the 6-month clinical benefit rate of first-time leuprolide acetate treatment of gross disease was 66% and progression-free survival was comparable to patients treated with chemotherapy. Leuprolide acetate regimens were heterogeneous, but significant toxicity was rare. These results support leuprolide acetate as safe and effective for the treatment of relapsed adult granulosa cell tumors in the second line and beyond.
复发性卵巢颗粒细胞瘤的最佳治疗方法尚不清楚。临床前研究和小病例系列研究表明，促性腺激素释放激素激动剂在治疗这种疾病方面具有直接的抗肿瘤活性，但关于这种方法的疗效和安全性知之甚少。
本研究旨在描述在一组复发性颗粒细胞瘤患者中使用醋酸亮丙瑞林的模式和临床结局。
这是一项回顾性队列研究，纳入了一家大型癌症转诊中心和附属县医院的罕见妇科恶性肿瘤登记处的患者。符合纳入标准的患者诊断为复发性颗粒细胞瘤，并接受醋酸亮丙瑞林或传统化疗作为癌症治疗。分别观察醋酸亮丙瑞林作为辅助治疗、维持治疗和治疗大体疾病的疗效和安全性。使用描述性统计方法总结人口统计学和临床数据。无进展生存期从治疗开始到疾病进展或死亡的日期计算，并使用对数秩检验比较组间差异。6 个月临床获益率定义为开始治疗后 6 个月内无疾病进展的患者百分比。
62 例患者共接受了 78 次含醋酸亮丙瑞林的治疗疗程，其中 16 例为复治。在这 78 个疗程中，57 个（73%）用于治疗大体疾病，10 个（13%）用于肿瘤减瘤手术后的辅助治疗，11 个（14%）用于维持治疗。患者在首次接受醋酸亮丙瑞林治疗前平均接受了 2 种（中位数，1-3 种）系统治疗方案。肿瘤减瘤手术（100%[62/62]）和铂类化疗（81%[50/62]）是首次使用醋酸亮丙瑞林前的常见治疗方法。醋酸亮丙瑞林治疗的中位持续时间为 9.6 个月（中位数，4.8-16.5）。近一半的治疗疗程为单一药物醋酸亮丙瑞林（49%[38/78]）。联合治疗方案最常包括芳香化酶抑制剂（23%[18/78]）。疾病进展是最常见的停药原因（77%[60/78]）；只有 1 例（1%）患者因不良事件停止使用醋酸亮丙瑞林。在治疗大体疾病时，首次使用醋酸亮丙瑞林的 6 个月临床获益率为 66%（95%置信区间，54-82）。无进展生存期与化疗后相比无统计学差异（10.3 个月[95%置信区间，8.0-16.0]与 8.0 个月[95%置信区间，5.0-15.3]；P=.3）。
在一组复发性颗粒细胞瘤患者中，首次使用醋酸亮丙瑞林治疗大体疾病的 6 个月临床获益率为 66%，无进展生存期与接受化疗的患者相当。醋酸亮丙瑞林的治疗方案具有异质性，但严重毒性罕见。这些结果支持醋酸亮丙瑞林作为二线及以上复发性成人颗粒细胞瘤安全有效的治疗方法。
