Advanced (>second) line chemotherapy in the treatment of patients with recurrent epithelial ovarian cancer

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Abstract

Objective

To explore the pattern of chemotherapy (beyond the second-line) used to treat patients with recurrent epithelial ovarian cancer (including primary peritoneal carcinoma).

Study design

This retrospective study included 156 patients with recurrent epithelial ovarian cancer and primary peritoneal carcinoma who were treated in the Gynecologic Oncologic Department at Meir Medical Center between November 1995 and December 2003. Clinical characteristics and data regarding the surgery, chemotherapy, and response to treatment were abstracted from the patients’ medical records to determine patient response to advanced lines of chemotherapy for recurrent epithelial ovarian cancer.

Results

Of the 156 patients, 63 (40%) were treated beyond second-line chemotherapy. Clinical response to third-line chemotherapy was 11.9% (6.8% had complete clinical response and 5.1% partial clinical response) and 3.4% had stable disease. A total of 17% did not show immediate progression, with a median progression free-interval of 1.5 months. A drastic decline in clinical response rates was shown beyond third-line chemotherapy. Any response to treatment in more advanced lines was consistently under 5%.

Conclusion

These results imply that advanced lines of chemotherapy are associated with low response rates, although a small percentage of patients showed some clinical response or remained with stable disease at the end of treatment. Along with patient preferences, the advantages and disadvantages of continued therapy should be considered, for the side effects of each treatment cannot be overlooked.

Introduction

Epithelial ovarian cancer (EOC) is the most commonly occurring gynecological cancer and the most common cause of death among women with gynecologic malignancies. The lifetime risk of ovarian cancer in the general population is 1.7% [1], with an age adjusted incidence rate of 13.5 cases per 100,000 women. Most patients are diagnosed with advanced disease and have very poor long-term survival [2], [3]. The currently recommended therapy for advanced-stage ovarian cancer is surgical cytoreduction followed by adjuvant chemotherapy based on carboplatin and taxane. Despite a high initial response rate to the primary treatment, eventually 75% of patients relapse and die of the disease [2], [4], [5]. The progression-free interval between the end of the initial treatment and recurrence is difficult to predict. The intent of treatment in the setting of recurrent disease is palliative and mainly consists of additional chemotherapy lines with lower response rates compared to that noted in the adjuvant first-line [6]. The choice of second-line chemotherapy agent is based on the treatment-free interval. Non-platinum drugs including doxil (liposomal doxorubicin), topotecan (hycamtin), taxol (paclitaxel), gemzar (gemcitabine), cytoxan, (cyclophosphamide), and VP-16 (oral etoposide), administered as a single agent are optional for short platinum-free interval recurrences (≤6 months) [6], [7]. Re-induction with a combined platinum-based regimen may be effective in chemosensitive patients (treatment-free interval >6 months) [8], [9]. A response to second-line therapy is observed in up to 60% of platinum-sensitive patients, with as many as 25% achieving complete response [8], [10]. The median progression-free survival (PFS) in these patients is 8–13 months, with a median survival of 15–29 months. The outcomes are best in women with a platinum-free interval of more than 24 months [11]. Response rates in patients with platinum resistance is lower; in the range of 20–40%, with a median PFS of 4–6 months and median survival of 12–15 months [12], [13], [14], [15]. Many patients are provided with further chemotherapy lines because the disease course is characterized by repeated episodes of recurrence or progression following limited periods of stable disease. Unlike the extensively published results of various second-line chemotherapy options, very limited information is available regarding response to chemotherapy beyond the second-line. The lack of evidence-based data limits the depth of discussion and informed consent before launching further treatment interventions following failure of second-line chemotherapy. The aim of the current study was to quantitatively characterize the results of advanced (>2) line chemotherapy.

Section snippets

Materials and methods

A retrospective analysis was conducted of patients with progression of EOC or primary peritoneal carcinoma (PPC) treated at Meir Medical Center, Kfar Saba, Israel, between January 1995 and December 2003. All patients had previously undergone cytoreductive surgery and completed 6 cycles of carboplatin (AUC = 6) and taxol (175 mg/m2) every 3 weeks. Patients were followed at the Gynecologic Oncology Clinic every 3–4 months for the first 3 years, then every 6 months, with a yearly follow-up after 5

Results

A total of 156 patients with recurrent disease following initial treatment were evaluable. The mean age at diagnosis was 62 years (range 31–88). The cohort included 42 (26.9%) patients above the age of 70 years and six younger than 40 years of age. Information regarding the pre-treatment WHO PS was recorded in two thirds of the files (n = 106) and showed that 83% of the patients had a PS of 0–2. Serous papillary adenocarcinoma was found in 76 patients (49%), and 48 tumors (31%) were defined as

Comment

The current study population included 156 patients with EOC or PPC, with epidemiological (age at diagnosis, origin, risk factors) and clinical (grading and staging) characteristics similar to those discussed in the literature [16], [17], [18], [19]. Examination of the study population histology subtype showed 48.7% EOC and 30.7% PPC. These results differ from the findings of other research groups such as Armstrong and colleagues [16], who found 85.5% EOC and 11.1% PPC in a study population of

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    These authors contributed equally to this work.

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