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 .
Docetaxel and carboplatin is an active regimen in advanced non-small-cell lung cancer: a phase II study in Caucasian and Asian patients.
BACKGROUND The purpose of this study was to report response rates , survival and toxicity in advanced non-small-cell lung cancer ( NSCLC ) following docetaxel and carboplatin , and to explore potential differences in these end points between Caucasian and Asian patients . PATIENTS AND METHODS Sixty-eight patients of good performance status with Stage IIIB or IV NSCLC were entered on a phase II study at three sites in Australia and Singapore .  Docetaxel 75 mg/m2 and carboplatin AUC 6 were given every 3 weeks . Response to treatment and toxicity were grade d by st and ard criteria . The Kaplan-Meier method was used to estimate survival rates , and subgroups compared by the log-rank test . Cox 's proportional hazards regression was used to determine which potentially explanatory variables independently affected the outcome . RESULTS The response rate was 39 % ( 95 % confidence interval 27 % to 52 % ) , and 42 % in evaluable patients . Response occurred in 65 % of Asian and 31 % of Caucasian patients ( P = 0.01 ) . Ethnicity was the only significant predictor of response in multivariate analysis . The 1-year survival rate was 53 % . Performance status ( P = 0.021 ) , ethnicity ( P = 0.035 ) and presence of bone or liver metastases ( P = 0.011 ) were independent predictors of overall survival . Neutropenia ( grade IV in 73 % of patients ) , febrile neutropenia ( 26 % patients ) and diarrhea ( grade III/IV in 11 % of patients ) were the major treatment related toxicities . A high rate ( three of six ) of febrile neutropenia in Singapore , including one treatment-related death in the initial patients treated , result ed in a reduction in the carboplatin dose to AUC 4.5 at that site . CONCLUSIONS This regimen is active in advanced NSCLC . The potential impact of ethnicity on efficacy and toxicity of treatment requires further investigation
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 .