OBJECTIVES: The optimal treatment for women with recurrent epithelial ovarian 
cancer is evolving. The objective of this review is to outline the transition 
away from platinum doublets toward nonplatinum combinations and review emerging 
data on antiangiogenesis therapy in this setting.
MATERIALS AND METHODS: Recently published and presented data as well as ongoing 
clinical trials are discussed.
RESULTS: Current clinical practice largely harmonizes with a paradigm that 
outlines a treatment algorithm for recurrent ovarian cancer based on the 
duration of platinum-free exposure. In this model, patients whose penultimate 
platinum compound exposure (platinum-free interval [PFI]) is longer than 6 
months are generally offered a platinum agent or a platinum-containing doublet; 
those with a shorter interval are usually treated with a single nonplatinum 
agent. This is based on the simple contention that better clinical outcomes will 
be realized with platinum in those deemed platinum sensitive (PFI >6 months). 
However, it is becoming clear from various phase II and phase III clinical 
studies that the performance of many nonplatinum chemotherapeutic agents is also 
influenced by this parameter (PFI). Indeed, although definitive comparisons of 
nonplatinum drugs to novel cytotoxic agents are lacking, the clinical activity 
of these compounds might approach or exceed that of platinum agents. Although 
recognized by clinicians, the dichotomy that determines therapy based on PFI has 
not been formally accepted by the US Food and Drug Administration in all cases 
of drug labeling. For instance, whereas the combination of gemcitabine and 
carboplatin is now approved for patients with platinum-sensitive recurrent 
ovarian cancer, traditionally used platinum-resistant (PFI <6 months) agents 
such as topotecan and pegylated liposomal doxorubicin are also approved by the 
US Food and Drug Administration as single agents in platinum-sensitive patients. 
Furthermore, the nonplatinum doublet pegylated liposomal doxorubicin and 
trabectedin has recently documented comparable activity to platinum combinations 
among patients with a PFI of longer than 6 months. To that end, the most 
prolific developmental therapeutics arena in ovarian cancer is biologically 
targeted therapy, particularly angiogenesis inhibitors. Although it is unknown 
if the clinical activity from these new agents will respect the 
chemotherapy-sensitive dichotomy, it is clear that they have the potential to 
augment efficacy, possibly in both traditionally chemosensitive and 
chemoresistant phenotypes.
CONCLUSIONS: The term platinum sensitive should probably be replaced by 
chemotherapy sensitive, particularly as new nonplatinum agents and combinations 
are identified as active in this setting. Nonplatinum doublets are effective in 
treating platinum-sensitive recurrent disease, and adding antiangiogenesis 
agents to these combinations is a research priority.