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 Grouping
Stage 1 T1 N0 M0
Stage IA T1a N0 M0
Stage IB T1b N0 M0
Stage IC T1c N0 M0
Stage II T2 N0 M0
Stage IIA T2a N0 M0
Stage IIB T2b N0 M0
Stage IIC T2c N0 M0
Stage III T3 N0 M0
Stage IIIA T3a N0 M0
Stage IIIB T3b N0 M0
Stage IIIC T3c
Any T
Stage IV Any T Any N M1