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 .
Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. The Cancer and Leukemia Group B.
BACKGROUND Both total dose and dose intensity of adjuvant chemotherapy are postulated to be important variables in the outcome for patients with operable breast cancer . The Cancer and Leukemia Group B study 8541 examined the effects of adjuvant treatment using conventional-range dose and dose intensity in female patients with stage II ( axillary lymph node-positive ) breast cancer . METHODS Within 6 weeks of surgery ( radical mastectomy , modified radical mastectomy , or lumpectomy ) , 1550 patients with unilateral breast cancer were r and omly assigned to one of three treatment arms : high- , moderate- , or low-dose intensity . The patients received cyclophosphamide , doxorubicin , and 5-fluorouracil on day 1 of each chemotherapy cycle , with 5-fluorouracil administration repeated on day 8 . The high-dose arm had twice the dose intensity and twice the drug dose as the low-dose arm . The moderate-dose arm had two thirds the dose intensity as the high-dose arm but the same total drug dose . Disease-free survival and overall survival were primary end points of the study . RESULTS At a median follow-up of 9 years , disease-free survival and overall survival for patients on the moderate- and high-dose arms are superior to the corresponding survival measures for patients on the low-dose arm ( two-sided P<.0001 and two-sided P = .004 , respectively ) , with no difference in disease-free or overall survival between the moderate- and the high-dose arms . At 5 years , overall survival ( average + /- st and ard error ) is 79 % + /- 2 % for patients on the high-dose arm , 77 % + /- 2 % for the patients on the moderate-dose arm , and 72 % + /- 2 % for patients on the low-dose arm ; disease-free survival is 66 % + /- 2 % , 61 % + /- 2 % , and 56 % + /- 2 % , respectively . CONCLUSION Within the conventional dose range for this chemotherapy regimen , a higher dose is associated with better disease-free survival and overall survival
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 .