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 .
Influence of comorbidities and age on risk of death without recurrence: a retrospective analysis of the Arimidex, Tamoxifen Alone or in Combination trial.
PURPOSE The Arimidex , Tamoxifen Alone or in Combination ( ATAC ) study was a double-blind r and omized trial in which postmenopausal women with early-stage breast cancer were assigned to receive anastrozole , tamoxifen , or the combination . We have conducted a retrospective analysis to examine the effects of comorbidities and age on treatment received , breast cancer-related mortality , and competing causes of mortality . PATIENTS AND METHODS The current analyses were based on 10-year median follow-up data in the two monotherapy arms ( anastrozole  , n = 3,092  ; tamoxifen  , n = 3,094 ) of the ATAC study . Baseline comorbidities and tumor and treatment characteristics were compared between women age less than 70 years and women age ≥ 70 years . The cumulative incidence of breast cancer-related and non-breast cancer-related mortality was assessed according to age and comorbidities . RESULTS One thous and six hundred sixty-two patients ( 27 % ) were age ≥ 70 years at study entry . Older women were more likely to undergo mastectomy ( odds ratio [ OR ] , 1.92 ; 95 % CI , 1.71 to 2.16 ) and less likely to receive radiotherapy ( OR , 0.49 ; 95 % CI , 0.44 to 0.55 ) or chemotherapy ( OR , 0.24 ; 95 % CI , 0.18 to 0.29 ) . Women age ≥ 70 years had an increased risk of recurrence compared with women age less than 70 years ( hazard ratio [ HR ] , 1.21 ; 95 % CI , 1.08 to 1.37 ) and a substantially increased risk of death without recurrence ( HR , 4.13 ; 95 % CI , 3.53 to 4.83 ) . The risk of death without recurrence increased with comorbidity score ( 10-year estimates of 8.4 % , 20.0 % , and 30.4 % for Satariano score 0 , 1 , and 2 + , respectively ; P < .001 ) . CONCLUSION Age influences the risk of recurrence , and age and comorbidities significantly influence the risk of death without recurrence . Formal assessment of comorbidities should be incorporated into decisions regarding adjuvant therapies
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 .