Ovarian Cancer (OC) and its management
Patients are treated over a continuum in which therapeutic choices may impact future therapies, and the management of toxicity is a major goal of therapy [Bukowski 2007].
The fact that most women with advanced ovarian cancer will experience progression after first-line therapy highlights the importance of identifying novel, effective agents for second-line chemotherapy [Vasey 2003; Fung-Kee-Fung 2007]. Few single agents other than platinum compounds are active in relapsed ovarian cancer (ROC), and approved agents include Pegylated Liposomal Doxorubicin (PLD), the topoisomerase I inhibitor topotecan, and the nucleoside analogue gemcitabine. Platinum-based combinations have demonstrated a superior efficacy than the carboplatin monotherapy [Parmar 2003, Pfisterer 2006, Pujade-Lauraine 2010]. Apart from re-induction with platinum compounds based on the duration of prior treatment-free interval [Salzberg 2005], pegylated liposomal doxorubicin is one of the approved standard agents frequently used in ROC [Perez-Lopez 2007; Markman 2004; Colombo 2006; Gordon 2001; Lorusso 2004; Ferrandina 2008; Gordon 2004]. Topotecan has also been commonly used as salvage therapy in these patients [Gordon 2001; McGuire 2000; Bookman 1998; Huinink 2004].
The effectiveness of platinum re-treatment in relapsed ovarian cancer is highly correlated with the platinum-free interval (PFI). A PFI ≥ 6 months predicts platinum sensitivity, but within this group, a PFI of 6-12 months is considered to indicate a partially platinum-sensitive disease [Poveda 2010]. Platinum-based therapy is generally accepted as standard in patients with PFI > 12 months, with response rates ranging from 30 to 60% [Kaye 2008]. Nevertheless, there is a high medical need for new effective therapies in the subset of patients with a PFI of 6 to 12 months [Yondelis® EPAR]. In this subpopulation single-agent PLD is most often recommended [NCCN guidelines 2010; Nice guidelines 2005].
Patients with an earlier relapse after first-line platinum-based chemotherapy (i.e. PFI <6 months) are defined as platinum-resistant [Markman 1991; Markman 1992]. Patients with platinum-resistant disease often have poor performance status, multiple disease sites, large tumour volume and mucinous or clear cell histologies [Poveda 2007], and non-platinum agents are chosen for further treatment. Compared to patients with platinum-sensitive disease, their response rate is lower [Fung-Kee-Fung 2007]. Therefore, in these patients the goal is to achieve adequate palliation [Vermorken 2008].
Table 2 (continued). American Joint Committee on Cancer (AJCC) TNM and FIGO . Staging System for Ovarian and Primary Peritoneal Cancer (7th ed., 2010).
|Stage IV||Any T||Any N||M1|