Guan et alr found that there was no statistically significant difference in 2 year overall survival HR 1.05 including 530 eligible patients (95% CI 0.61-1.81, p=0.85) as well as 3 year overall survival HR 1.12 including 480 eligible patients (95% CI 0.68-1.86, p=0.65). However 5 year overall survival favoured the three weekly regimen HR=1.79 (95%CI 0.97-3.31, p=0.06), although still not statistically significant. Locoregional recurrence free survival did not demonstrate any difference between groups at 1 year (HR=1.26, 95%CI 0.46-3.46, p=0.65) or 2 years (HR= 1.14, 95% CI 0.51-2.56, p=0.74). This meta-analysis is limited by the use of low level evidence such as retrospective and case series data inclusion, but in general suggests no major differences.
Strojan et alr examined the impact of cumulative dose on mortality. They found a relatively linear dose response with the highest benefit occurring with delivery of the greatest amount of cisplatin. For the 100 mg/m2, 3 weekly regimen the maximum dose is 300 mg/m2, for the 40 mg/m2, weekly dose the cumulative maximum is 280 mg/m2. These doses are broadly similar and suggest again that the weekly schedule is not unreasonable, although there is no direct prospective comparative data.
There is controversy regarding the optimal schedule of cisplatin. Recent retrospective datar showed no difference, but a prospective study demonstrated inferiority of lower dose weekly treatment.r There is a direct dose response relationship demonstrated and it is likely that the delivered cumulative dose is the most critical variable.r Overall there is evidence that the total cumulative dose of cisplatin is important. There appears to be a threshold for efficacy at 200 mg/m2, thus maximum doses of cisplatin should be aimed for, with the intention of achieving at least 200 mg/m2.
Forest plots of hazard ratios for OS and LRFSr
Forest plots of hazard ratios for 2-year, 3-year and 5-year OS in patients between weekly and three weekly cisplatin chemoradiotherapy OS=overall survival, CI=confidence interval, I2=index of heterogeneity
Forest plots of hazard ratios for 1-year and 2 -year LRFS in patients between weekly and three weekly cisplatin chemoradiotherapy. LRFS= Locoregional recurrence-free survival. CI= confidence interval, I2=index of heterogeneity.
© Oncotarget 2016