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 .
Relationship between toxicity and obesity in women receiving adjuvant chemotherapy for breast cancer: results from cancer and leukemia group B study 8541.
PURPOSE We examined data from a large clinical trial to determine if chemotherapy dosing according to actual body weight places obese patients at greater risk of toxicity . PATIENTS AND METHODS Cancer and Leukemia Group B ( CALGB ) study 8541 , a r and omized study of schedule and dose of adjuvant cyclophosphamide , doxorubicin , and fluorouracil ( CAF ) for stage II breast cancer patients with positive regional lymph nodes , provided data on 1,435 women for analysis . Using body-mass index ( BMI ) , we classified a woman as obese if her BMI was > or = 27.3 kg/m2 ; doses were considered weight-based if within 5 % of values calculated using actual weight . Our primary analysis concerned toxicity risks during cycle 1 . RESULTS Among women who received weight-based doses of the most dose-intensive CAF regimen , 47 % of obese and 51 % of nonobese women experienced severe hematologic toxicity ( grade > or = 3 ) during cycle 1 ( P = .51 , two-tailed ) . The overall risk ratio ( obese v nonobese ) of treatment failure among women who received weight-based doses during cycle 1 was 1.02 ( 95 % confidence interval , 0.83 to 1.26 ) , stratified by treatment and adjusted for number of positive nodes , menopausal status , hormone receptor status , and tumor size . The overall adjusted failure risk ratio ( weight-based v reduced initial doses ) was 0.73 ( 95 % confidence interval , 0.53 to 1.00 ) among obese women . CONCLUSION Obese patients initially dosed ( within 5 % ) by actual weight did not experience excess cycle 1 toxicity or worse outcome compared with nonobese women dosed similarly . The data suggest that obese women who received reduced doses in cycle 1 experienced worse failure-free survival . We recommend that initial doses of CAF be computed according to actual body weight
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 .