Secondary cytoreduction plus oxaliplatin-based HIPEC in platinum-sensitive recurrent ovarian cancer patients: A pilot study
Introduction
Conventionally, between 60% and 70% of patients with ovarian carcinoma recur [1], [2], [3], [4], [5], and their prognosis and quality of life are obviously poor. Although some advances have been made in order to standardize the best clinical approach to face up the recurrence, such as the definitive role of secondary cytoreductive surgery [6], the need to identify new integrated treatment still remains an important issue in this group of patients with unfavorable prognosis. Among new treatment options, intraperitoneal hyperthermic chemotherapy (HIPEC) has been proposed. The reason is that recurrent ovarian cancer is often a locoregional disease, involving only the peritoneum and adjacent intra-abdominal organs, making it ideally suited for locoregional therapy. Moreover, intraperitoneal delivery of chemotherapy in ovarian cancer has been shown to be effective in front-line treatment [7], [8], [9]. The possible synergy between hyperthermia and chemotherapy agents has sparked clinical trials using this combination in many disease types. With regard to analogous situations with ovarian carcinoma, in which disease may be widespread within the peritoneal cavity, studies in gastric cancer [10], malignant mesothelioma [11], appendix cancer [12], and colorectal cancer have shown promising results [13]. As far as ovarian carcinoma is concerned, the few clinical studies looking at HIPEC following surgical debulking [14], [15], [16] suffer from some limits: relatively small numbers of patients, retrospective studies, different clinical settings and drugs. In order to contribute to a better definition of the role of HIPEC during secondary cytoreduction (CRS), we treated prospectively a selected group of platinum-sensitive recurrent ovarian cancer patients with CRS and oxaliplatin (OXA)-based HIPEC, followed by systemic chemotherapy with OXA and docetaxel (DTX). We considered the choice of OXA as a valid option, due to its efficacy as a single agent in recurrent platinum-sensitive ovarian cancer patients, its synergistic activity with paclitaxel, its favorable toxicity profile and its potential use in case of carboplatin sensitivity [17], [18]. Moreover, it has been still utilized for the intraperitoneal perfusion showing feasibility and safety [19], [20]. As far as DXT is concerned, it is recognized as equiactive and less (neuro)toxic when compared with paclitaxel [21] and we recently showed an encouraging neurotoxicity profile for the combination of DTX/OXA in the same clinical setting, besides its efficacy in terms of overall response rate and duration of response [22]. Feasibility, toxicity and efficacy of the whole treatment are presented.
Section snippets
Study design
This is a single-institutional pilot study aimed at evaluating the activity of the hyperthermic intraperitoneal chemotherapy with oxaliplatin associated with optimal cytoreduction and followed by systemic administration of the combination of DTX and OXA in recurrent platinum-sensitive ovarian cancer patients. The primary end point of the study was the assessment of treatment efficacy in terms of disease free survival (DFS) and time to progression (TtP). Overall survival (OS) as well as the
Results
From May 2005 to September 2008, a total of 28 recurrent ovarian cancer patients were treated with optimal cytoreduction and HIPEC at the Division of Gynecologic Oncology of the Catholic University of the Sacred Heart in Rome and Campobasso. Three patients were treated outside the study. Two of them were enrolled in a phase 2 protocol of HIPEC for platinum-resistant patients, which was promptly closed for the low accrual's rate. They both died within six months from the end of treatment. The
Survival analysis
With a median follow-up time of 18 months (range 3–38), 7 patients (28%) have relapsed after a median time of 10 months (range 6–17) from CRS + HIPEC. Six cases have a serous histological type and 1 has a clear cell carcinoma. The pattern of recurrence was distributed as follows: 2 only intrabdominal with diffuse carcinomatosis, 2 distant lymphnodal metastases. In 3 patients, recurrence was mixed (intra-abdominal and distant or intraparenchimal). All cases were submitted to salvage chemotherapy
Discussion
Results from the 5th International Workshop on Peritoneal Surface Malignancy have validated the definitive potential role of HIPEC and CRS in ovarian cancer [30]. However, although the growing number of studies available in the literature, they fail to reach level I–II of evidence [31] and call for further verifications. Since randomized studies regarding this topic have found some difficulties in the accrual of the patients, at the moment much information should be obtained throughout
Conflict of interest statement
The authors declare that there are no conflicts of interest.
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