Controversies on the treatment of ovarian cancer with dose-dense chemotherapy

Epithelial ovarian cancer is the most lethal gynaecological malignancy with an estimated 295,414 new cases and 184,799 deaths around the world. Cytoreductive surgery and combination chemotherapy have remained a standard therapy for decades. The majority of women diagnosed with ovarian cancer will receive systemic chemotherapy for recurrent or advanced diseased. In recent years, therapies such as anti- angiogenics, PARP inhibitors, and dose-dense chemotherapy have emerged as novel strategies against ovarian cancer. Dose-dense chemotherapy, usually with a carboplatin and paclitaxel regimen, has been proposed as an alternative to conventional chemotherapy for these patients. However, the results for different trails are inconsistent and dose-dense chemotherapy remains controversial. Results from the JGOG 3016 study showed a progression free survival and overall survival benefit, with increased neurotoxicity and anaemia. While the GOG 262, MITO-7, GOG 252 and ICON8 studies found no benefit on progression free survival, with a recent meta-analysis concluding that three weekly chemotherapy remains the standard of care. Ovarian cancer molecular subtypes and differences in pharmacogenetics between populations may explain the differences in response to dose dense chemotherapy, however our understanding of this factors is still lacking. Here, we reviewed the evidence for and against dose-dense chemotherapy and the possible factors for the different results among trials.