Medical Oncology, vol. 24, no. 1, 39–43, 2007 © Copyright 2007 by Humana Press Inc. All rights of any nature whatsoever reserved. 1357-0560/(Online)1559-131X/07/24:39–43/$30.00
Original Article
The Efficacy of Tamoxifen in Patients with Advanced Epithelial Ovarian Cancer Hakan Karagol,1 Pinar Saip,2 Kazim Uygun,1 Murat Caloglu,3 Yesim Eralp,2 Faruk Tas,2 Adnan Aydiner,2 and Erkan Topuz2 1Department
of Medical Oncology and 3Department of Radiation Oncology, Faculty of Medicine, Trakya University and 2Department of Medical Oncology, Institute of Oncology, Istanbul University, Turkey
Abstract Background: Activity of tamoxifen as a salvage therapy in patients with advanced epithelial ovarian cancer was evaluated by a number of studies. In this study, we evaluated efficacy of tamoxifen in our patients with platinum-resistant epithelial ovarian carcinoma. Patients and Methods: A retrospective analysis was conducted of patients who received tamoxifen at a dose 20 mg twice daily for the treatment of advanced epithelial ovarian cancer. Results: Twenty-nine eligible patients were included to the study. There were 1 (3%) complete response, 2 (7%) partial response, 6 (21%) stable disease, and 20 (69%) progressive disease. All patients were progressed after initiation of tamoxifen. Median progression-free survival was 4 mo (95% CI: 2.98–5.02). Disease progression of 19 (65%) patients were shown within the first 6 mo after initiation of tamoxifen. Progression-free survival was between 6 and 12 mo for 7 (24%) patients and ≥12 mo for 3 (10%) patients. The median survival after initiation of tamoxifen was 15 mo (95% CI: 7.2–22.8). No toxicity attributable to tamoxifen was seen in any of the patients. The only independent prognostic factor that had a significant predictive value for progression-free survival was the response to tamoxifen treatment (p = 0.043, hazard ratio: 0.12, 95% CI: 0.01–0.94). Conclusion: Considering minimal side effects and ability to cause objective responses, there is a place for tamoxifen in treatment of patients with platinum-resistant ovarian cancer. A phase III trial is required to confirm the value of the drug in patients presenting these clinical settings. Key Words: Ovarian cancer; tamoxifen.
Despite this fact, a majority of women with the advanced disease will ultimately relapse and develop drug-resistant disease (1,2). Several second-line treatment options are available in the setting of recurrent disease, which includes re-treatment with the original drugs and use of other cytotoxic agents (2). Although responses to second-line chemotherapy is not unusual, responses tend to be brief and long-term survival rare (3). Activity of tamoxifen, a nonsteroidal triphenylethylene derivative, as a salvage therapy in patients with
Introduction Ovarian cancer is one of the most sensitive of all solid tumors to chemotherapy, and responses are expected in over 80% of women who received standart platinum and paclitaxel-based treatment.
Received August 7, 2006; Accepted October 26, 2006. Hakan Karagol, Trakya Universitesi Tip Fakultesi Ic Hastaliklari Tibbi Onkoloji Bilim Dali, 22030, Edirne, Turkey. E-mail:
[email protected]
39
40 advanced epithelial ovarian cancer was evaluated by a number of studies (4–8). The therapeutic efficacy of tamoxifen in cancer therapy is thought to arise primarily from its antiproliferative action by binding competitively to the estrogen receptor, thereby blocking the mitogenic effect of estradiol. Tamoxifen is also able to induce apoptosis by induction of oxidative stress, followed by mitochondrial dysfunction and activation of caspases (9,10). Moreover, tamoxifen has been shown to delay the development of resistance to cisplatin in vitro for an ovarian carcinoma cell line (11). In this study, we evaluated the efficacy of tamoxifen in our patients with platinum-resistant epithelial ovarian carcinoma.
Materials and Methods Patient Characteristics Patients selected for inclusion in this study had to satisfy all of following criteria; (a) patients with histologically confirmed epithelial ovarian carcinoma, (b) patients with platinum-resistant disease (responded to platinum-based chemotherapy but demonstrated recurrence within 6 mo of completing platinum-based chemotherapy or progressed during platinum-based chemotherapy). During the period from January 1990 to December 2003, 31 patients with platinum-resistant epithelial ovarian carcinoma received tamoxifen at a dose 20 mg twice daily for the treatment of the disease in our medical oncology department. Two of 31 patients were excluded from the study because of lack of data in their files. Table 1 shows characteristics of 29 eligible patients.
Response Assessment, Survival, and Statistical Analysis Complete response was defined as the disappearance of all signs of the disease in response to treatment. Partial response was defined as at least a 50% reduction in the product of the two diameters of measurable disease or at least a 50% fall in the CA125 titer, comfirmed by a second measurement 4 wk later. Progressive disease was defined as a progressive rise in the CA-125 titer, taken on two different occasions at least 4 wk apart, and/or any increase in the size of measurable disease. All other
Medical Oncology
Karagol et al. Table 1 Patient Characteristics Characteristics
n(%)
Median age (min–max) 56 (26–71) Menapousal status Pre Peri Post Histology Serous Endometrioid Undifferentiated Mucinous Clear Cell Mixed Grade I II III Unknown FIGO stage at diagnosis I II III IV Number of prior chemotherapeutic regimen 1 2 3
29 (100) 4 (14) 4 (14) 21 (72) 21 (72.5) 3 (10) 2 (7) 1 (3.5) 1 (3.5) 1 (3.5) 0 11 (38) 9 (31) 9 (31) 1 (3.5) 0 18 (62) 10 (34.5) 3 (10) 12 (41) 14 (49)
situations were called stable disease. Progressionfree survival was accepted as the period from the first day of tamoxifen treatment to the first evidence of progression or death without progression. Survival after initiation of tamoxifen was defined as the period from first day of tamoxifen treatment to death. Age, histologic subtype, tumor grade, FIGO stage, number of prior chemotherapeutic regimen, and response to tamoxifen treatment were evaluated as prognostic factors related with progression-free interval. Survival analysis was performed with the Kaplan–Meier method. Univariate associations with the survival were analyzed by the log-rank test. Cox regression analysis was applied to identify independent prognostic factors. A p value 55) Histology (Serous vs Others) Grade (I–II vs III) FIGO Stage at diagnosis (I–III vs IV) Number of prior chemotherapeutic regimen (≤2 vs >2) Response to tamoxifen treatment (Complete or partial vs stable or progressive)
Univariate (p value)
Multivariate (p value)
NS (>0.1)
—
NS (0.064)
NS*
NS(>0.1)
—
NS(>0.1)
—
NS (0.082) 0.012
NS* 0.043*
* Prognostic factors that univarite analysis showed a p value
