This review shows that a significant proportion of patients in curative-intent clinical trials experience toxicities that result in dose modifications-dose reduction , dose delays or missed doses-despite strict selection criteria and intense monitoring .
Toxicities of systemic cancer therapies are often less frequently observed in clinical trials than in clinical practice , due to the careful selection of patients with fewer comorbidities .
Although guidelines exist for the estimation of chemotherapy dose , clinical factors like age , comorbid illness and extremes of body habitus are not considered in the method of dose calculation , which can result in significant toxicity .
Lack of Cumulative Toxicity Associated With Cabazitaxel Use in Prostate Cancer
Abstract Cabazitaxel provided a survival advantage compared with mitoxantrone in patients with castration-resistant prostate cancer refractory to docetaxel .  Grade 3 to 4 ( G3–4 ) neutropenia and febrile neutropenia were relatively frequent in the registrative XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer ( TROPIC ) trial , but their incidence was lower in the Exp and ed Access Program ( EAP ) . Although cumulative doses of docetaxel are associated with neuropathy , the effect of cumulative doses of cabazitaxel is unknown . In this retrospective review of prospect ively collected data , the authors assessed “ per cycle ” incidence and predictors of toxicity in the Italian cohort of the EAP , with a focus on the effect of cumulative doses of cabazitaxel . The study population consisted of 218 Italian patients enrolled in the cabazitaxel EAP . The influence of selected variables on the most relevant adverse events identified was assessed using a Generalized Estimating Equations model at univariate and multivariate analysis .“Per cycle ” incidence of G 3 to 4 neutropenia was 8.7 % , whereas febrile neutropenia was reported in 0.9 % of cycles . All events of febrile neutropenia occurred during the first 3 cycles . Multivariate logistic regression analysis showed that higher prior dose of cabazitaxel was associated with decreased odds of having G3 to 4 neutropenia ( OR = 0.90 ; 95 % CI : 0.86–0.93 ; P < 0.01 ) , febrile neutropenia ( OR = 0.52 ; 95 % CI : 0.34–0.81 ; P < 0.01 ) and G3 to 4 anemia ( OR = 0.93 ; 95 % CI : 0.86–1 ; P = 0.07 ) . Patients with a body surface area > 2 m2 presented increased odds of having G 3 to 4 neutropenia ( OR = 0.93 ; 95 % CI : 0.86–1 ; P = 0.07 ) , but decreased odds of having G3 to 4 anemia . Among the toxicities assessed , the authors did not identify any that appeared to be associated with a higher number of cabazitaxel cycles delivered . Prior cumulative dose was associated with reduced G3 to 4 neutropenia and anemia . The apparent protective effect associated with higher doses of cabazitaxel is likely to be affected by early dose reduction and early toxicity-related treatment discontinuation . Because this analysis is limited by its retrospective design , prospect i ve trials are required to assess the optimal duration of cabazitaxel treatment
This review shows that a significant proportion of patients in curative-intent clinical trials experience toxicities that result in dose modifications-dose reduction , dose delays or missed doses-despite strict selection criteria and intense monitoring .
Toxicities of systemic cancer therapies are often less frequently observed in clinical trials than in clinical practice , due to the careful selection of patients with fewer comorbidities .
Although guidelines exist for the estimation of chemotherapy dose , clinical factors like age , comorbid illness and extremes of body habitus are not considered in the method of dose calculation , which can result in significant toxicity .