Advanced stage mucinous epithelial ovarian cancer: The Hellenic Cooperative Oncology Group experience

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Abstract

Objective

Mucinous epithelial ovarian cancer (mEOC) representing about 10% of all EOC are known to be possibly resistant to platinum-based chemotherapy and bear a poorer prognosis with respect to other subtypes of EOC. This study was undertaken to compare response and survival to platinum-based chemotherapy between patients with advanced stages III and IV mEOC and serous EOC (sEOC).

Methods

A retrospective analysis was performed in 47 patients with advanced stage of mEOC treated with first-line platinum-based chemotherapy in the context of several study protocols of the Hellenic Cooperative Oncology Group (HeCOG) between 6/7/1983 and 25/2/2003. The outcome was compared to that of 94 patients with sEOC treated with the same protocols during the same study period (ratio mucinous: serous 1:2).

Results

One hundred forty-one patients (47 stages III and IV mEOC, 94 stages III and IV sEOC) treated with platinum-based chemotherapy were analyzed. The overall response rate for mEOC was 38.5% (complete remission 18%) (95% CI 23.4–55.4%) and 70% (complete remission 47%) (95% CI 58.5–80.3%) for sEOC (P = 0.001). After a median follow-up of 77.8 months, median survival and time to tumor progression (TTP) were not significantly different between the two groups (33.2 months [95% CI 23.3–43.1 months] vs. 38.0 months [95% CI 26.8–49.2 months], P = 0.46, 11.8 months [95% CI 7.2–16.4 months] vs. 20.0 months [95% CI 15.7–24.2 months], P = 0.18, respectively).

Conclusion

Patients with mEOC have significantly lower response to first-line platinum-based chemotherapy compared to patients with sEOC. This low response to platinum-based chemotherapy was not translated in inferior TTP or survival. Our data indicate that a new strategy for chemotherapy in mEOC should be adopted, one that focuses on new agents without cross-resistance to platinum agents.

Introduction

Ovarian cancer is a major cause of morbidity and mortality among gynecological malignancies [1]. The current standard treatment of epithelial ovarian cancer (EOC) of all histological subtypes involves primary optimal debulking surgery followed by cisplatin-based chemotherapy. Despite, however, the significant advances in surgery and chemotherapy achieved over the past decades, the resulting overall 5-year survival rate remains quite low, approximately 30–40% [2], [3], [4]. This is mainly attributed to the fact that patients usually present with advanced stage disease as well as to the lack of effective therapies [5].

Mucinous epithelial ovarian cancer (mEOC) of all stages accounts for 11.2–19.9% of primary EOC [6]. In randomized clinical trials using platinum-based chemotherapy, the incidence of patients with advanced mEOC ranged from 2.4% to 5.2% [7], [8], [9], [10], [11]. Little is known about the variation of response and survival rates in women with mEOC, as only few studies have assessed the mucinous subtype of ovarian cancer [12], [13], [14]. Two or three studies have reported a poorer outcome of platinum-based chemotherapy in patients with mEOC compared to those with other histological subtypes [12], [13], [14], [15]. However, McGuire et al. [7] and ICON3 collaborators [11] concluded that they did not modify the management of mEOC when the histological subgroups were analyzed separately.

Since mEOC seems to have a different biological behavior than sEOC, which represents the most common histopathological subtype, we retrospectively investigated the outcome of platinum-based chemotherapy in stages III and IV mEOC patients.

Section snippets

Patients and methods

Between July 1983 and February 2003, a total of 1446 patients with EOC underwent primary treatment at different centers of the Hellenic Cooperative Oncology Group (HeCOG). Of this group of patients, 47 were originally diagnosed with stages III and IV mEOC through the medical records and the electronic tumor registry of HeCOG. All pathologic specimens from primary surgery were examined by expertise pathologists of the referral centers with a great experience in gynecological malignancies.

Results

Patients' characteristics are demonstrated in Table 1. The median age was 62 years (range 30–79 years) for the study group and 61 years (range 25–77 years) for the control group; this difference was not statistically significant. The median duration of follow-up was 77.8 months (range 0.3–225.8 months). The rates of stage III (64% vs. 64%) and stage IV (36% vs. 36%) were similar in both groups. At the completion of primary surgery, 27% of patients had residual disease <2 cm in the study group

Discussion

Our study was undertaken to compare response and survival to platinum-based chemotherapy between patients with advanced stages III and IV mEOC and sEOC. Recently, a body of evidence has been accumulated to support the contention that mEOC possibly demonstrates a distinctly different clinical behavior from the other EOC. Few clinical studies have evaluated the response to platinum-based regimens in mEOC. The Gynecological Oncology Group (GOG) evaluating cisplatin, cyclophosphamide ± doxorubicin

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