Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Surgery

Cytoreduction is often employed,[1] but such intervention has not been studied in the setting of a randomized clinical trial.

Systemic treatment options for patients with recurrent disease are subdivided as follows:

1. Platinum-sensitive recurrence: for patients whose disease recurs more than 6 months after cessation of the induction (usually retreated with a platinum and referred to as potentially platinum sensitive).
2. Platinum-refractory or platinum-resistant recurrence: for patients who progress prior to cessation of induction (platinum refractory) or within 6 months after cessation (platinum resistant); in these patients, platinums are deemednot useful.

Considerably higher response rates and response durations are achievable at retreatment with platinums alone or in combination when the disease is potentially platinum sensitive rather than when it is platinum resistant.

PLATINUM-SENSITIVE RECURRENCE

A small randomized study showed a significant difference in response rates and in duration of response in favor of a platinum-containing regimen over paclitaxel.[2] Several larger randomized trials have addressed whether the use of a platinum in combination is superior to single agents (see Table 2). A platinum-plus-paclitaxel combination yielded a superior outcome in terms of response rates, progression-free survival (PFS), and overall survival (OS) in comparison to carboplatin as a single agent or other platinum-containing combinations as control in an analysis of data analyzing jointly the results of three trials performed by the Medical Research Council/Arbeitsgemeinschaft Gynaekologische Onkologie (MRC/AGO) and ICON investigators (known as ICON4). These trials differed with respect to platinum-free interval, number of prior regimens allowed, and whether exposure to a prior taxane was required. Platinum plus paclitaxel was compared to several control regimens, though 71% used carboplatin as a single agent in the control, and 80% used carboplatin plus paclitaxel. Prolonged PFS (hazard ratio [HR] = 0.76; 95% confidence interval [CI], 0.66–0.89; P = .004) and overall survival (HR = 0.82; 95% CI, 0.69–0.97; P = .023) were improved in the platinum-plus-paclitaxel arm.[3][Level of evidence: 1iiA]

Table 2. Platinums and Platinum-based Drug Combinations Studied in Second-line Randomized Trials

The combination of carboplatin plus epirubicin has also been tested in randomized trials, but a survival advantage has not been observed for the combination versus carboplatin alone. Carboplatin plus pegylated liposomal doxorubicin has been studied in phase II trials but the results are only available in abstract form.[7] While platinum plus taxane is considered the standard option for a platinum-sensitive recurrence, particularly in the absence of residual neurotoxicity, the superior results might have as readily been achieved with this combination by using the single agents given sequentially, or with any of the combinations shown in Table 2.