Primary and acquired platinum-resistance among women with high grade serous ovarian cancer
Introduction
Though ovarian cancer only accounts for approximately 3% of cancer cases among women, it is one of the most deadly. In 2015, it is estimated that there will be approximately 21,000 new ovarian cancer cases, and more than 14,000 women will die from the disease [1]. Though most patients will achieve remission with front-line platinum-based chemotherapy, up to 80% of these women will recur [2].
Upon relapse, ovarian cancer patients are classified according to the length of time since they last received a platinum agent. Patients who relapse within six months of completing initial platinum therapy are primary platinum-resistant. These women carry a poor prognosis, with response rates to subsequent lines of therapy ranging from 7 to 20%. Patients who relapse more than 6 months following primary platinum therapy are considered to be platinum-sensitive. In contrast to platinum-resistant patients, women who are platinum-sensitive can expect response rates of 30–90% to additional platinum agents, with higher response rates noted in patients with a longer platinum-free interval. Unfortunately, almost all platinum-sensitive patients will eventually develop resistance, at which point they are considered to have acquired platinum-resistance [3], [4], [5], [6].
The poorer prognosis of platinum-resistant ovarian cancer as compared with platinum-sensitive ovarian cancer is well-documented. However, there is no published data evaluating outcomes in the acquired platinum-resistant population. The purpose of this study is to describe survival among women with acquired platinum-resistance as compared with women with primary platinum-resistance in a cohort of patients with high grade serous ovarian cancer.
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Materials and methods
A retrospective review was conducted of women with high grade serous ovarian cancer treated at The University of Oklahoma Health Sciences Center between January 2000 and December 2010. Approval was obtained from the Institutional Review Board (IRB) prior to initiating the study. As no data was collected prospectively, a waiver of informed consent was granted by the IRB. Women were excluded from the study if there was no histologic confirmation of their diagnosis, the status of platinum
Results
Of the 330 women included in the study, the majority presented with stage III (72.4%) or stage IV (15.8%) disease. In total, 81 (25%) women were primary platinum-resistant. Of the remaining 249 patients, 55 (22%) developed acquired platinum-resistance during the study period. Demographic and clinical characteristics of these groups are summarized in Table 1.
Discussion
Given that platinum-based chemotherapy is currently the mainstay of therapy for high-grade serous ovarian cancer, platinum-resistance is a major limitation in the management of this disease. In the present study, 25% of patients had primary platinum-resistant ovarian cancer and an additional 22% developed acquired platinum resistance during the follow-up period. There were few patients identified with acquired platinum resistance. However, this is likely due to the relatively small proportion
Potential conflicts of interest
KMM is on the advisory boards of Astra Zeneca, Immunogen, Clovis, Genentech Roche, and Merrimack. All other authors report no conflicts.
References (16)
- et al.
“Platinum resistant” ovarian cancer: what is it, who to treat and how to measure benefit?
Gynecol. Oncol.
(2014) - et al.
Treatment of relapsed carcinoma of the ovary with cisplatin or carboplatin following initial treatment with these compounds
Gynecol. Oncol.
(1990) - et al.
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eur. J. Cancer
(2009) - et al.
Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy
Gynecol. Oncol
(2016) - et al.
Cancer statistics, 2015
CA Cancer J. Clin.
(2015) Extending the platinum-free interval in recurrent ovarian cancer: the role of topotecan in second-line chemotherapy
The oncologist.
(1999)- et al.
Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin
J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol.
(1991) - et al.
Second-line therapy with paclitaxel and carboplatin for recurrent disease following first-line therapy with paclitaxel and platinum in ovarian or peritoneal carcinoma
J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol.
(1998)
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