On subgroup analysis, suboptimally debulked patients with residual disease of >1 cm (n = 342) had a significantly higher median overall survival in the dose dense arm (51.2 versus 33.5 months, HR-0.75, 95% CI 0.57 0.97, p = 0.027).
The dose-dense arms of MITO-7 and JGOG-3016 as well as the ethnic heterogeneity will be further addressed.
Median PFS did not differ significantly (17.3 months and 18.3 months; p = 0.66) between the standard and dose-dense arms, respectively.
There were no neutropaenia-related deaths, and fewer cases of grade 4 neutropaenia were encountered in the dose-dense arms of the study.
Citron et al (2003) however showed a significant improvement in overall survival with dose-dense therapy (risk ratio=0.69, P=0.013), with 3-year overall survival of 92% in the dose-dense arms and 90% in the 3 weekly arms.
In addition, there were comparable rates of haematological and non-haematological toxicities, and only 12% Grade 3/4 diarrhoea observed in the dose-dense arm.
Quality of life was reported to be significantly better in the dose-dense arm (p < 0.0001), which was discordant with the JGOG-3016 quality of life data [ 25].
This translated into an estimated 5-year PFS of 71% in the triple-negative cohort treated by high-dose compared with only 26% in the dose-dense arm.
Patients in the dose-dense arm (N=641 evaluated) were additionally randomised to receive or not receive epoetin alfa (haemoglobin at 12.5 13 g dl−1).
The most pronounced benefit of dose-intensified chemotherapy was observed in triple-negative tumors: In this subgroup, median PFS was not reached in the high-dose arm, whereas it was only 32.3 months in the dose-dense arm.
In the Arbeitsgemeinschaft Gynäkologische Onkologie phase III study, the rate of grade 3 4 skin toxicity observed in the intense sequential dose-dense arm (epirubicin, paclitaxel, followed by cyclophosphamide) was less than 5%, though the rates of grade 1 and 2 events reported as high as 31 and 15% cannot be ignored (Moebus et al, 2010).
