The choice of chemotherapy in women with relapsed epithelial ovarian cancer (EOC) is influenced by the duration of the platinum-free interval, the length of time from the last platinum-based cycle to the time of disease progression. Women who relapse within one month of receiving platinum therapy or who progress on therapy are considered to be platinum-refractory; women who relapse between one and six months after platinum therapy are considered to be platinum-resistant; and women who relapse more than six months after platinum therapy are considered to be platinum-sensitive. The latter group is further subgrouped by women who relapse between six and 12 months after platinum therapy (partially platinum-sensitive) and those who relapse after 12 months.
Doxirubicin hydrochloride is an anti-cancer drug that works by interfering with cancer cell DNA. A newer form of doxorubicin called pegylated liposomal doxorubicin (PLD) has been developed with a coating that allows it to reach higher concentrations in cancer cells and with less adverse effects on the heart.
We conducted this review to determine whether PLD was effective and safe compared with other drugs used for relapsed EOC.
We searched electronic databases and other resources for studies of PLD for relapsed ovarian cancerEOC, and included 14 studies up to October 2012. Most of these studies (12/14) were funded by drug manufacturers with a commercial interest in PLD (two studies) or the comparator drugs (10 studies). For women with platinum-sensitive relapsed EOC, we pooled data from two studies (1164 participants) that compared carboplatin plus PLD (PLD/carbo) with standard treatment (paclitaxel plus carbo (PAC/carbo)). Women survived for a similar length of time overall on these two treatments but the cancer took longer to progress in those receiving PLD/carbo. Women who received PLD experienced more severe low blood cell counts than the standard treatment. By comparison, women in the standard treatment group experienced more severe hair loss, nerve damage, allergic reactions, and joint and muscle pain. More women in the standard treatment group stopped treatment early suggesting that PLD/carbo was better tolerated than standard treatment. We concluded that PLD/carbo was a better treatment option than PAC/carbo for platinum-sensitive relapsed EOC.
Five studies compared PLD to five other chemotherapy drugs. The numbers of participants in these studies ranged from 97 to 829 women and we did not pool these data. PLD worked as least as well as the other agents and was comparatively well-tolerated. In all studies, hand-foot syndrome (HFS: swollen, painful, red, cracked and peeled soles and palms) occurred more frequently in the PLD group.
Three studies compared PLD plus another drug (canfosfamide (CAN), vintafolide (EC145) or trabectedin (TBD)) to PLD alone. The final results of the CAN study were not reported. The numbers of participants in the other studies ranged from 149 to 672 women and we did not pool these data. Women receiving the PLD/TBD combination treatment progressed six weeks later than those getting PLD only, however they did not live longer overall, and the combination treatment was associated with additional harmful effects. EC145 may improve survival in women with platinum-resistant relapsed ovarian cancer when combined with PLD; this combination is currently under investigation in a large trial. Although HFS can be severely disabling, we noted that it occurred much less frequently when lower doses of PLD were used.
Quality of the evidence
We consider the evidence related to the longer time to cancer progression with PLD/carbo for platinum-sensitive relapsed ovarian cancer to be of a high quality. There is currently insufficient evidence to support the use of other PLD combination treatments in relapsed EOC.