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 .
Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial.
CONTEXT Adjuvant fluorouracil has been shown to be of benefit for patients with resected pancreatic cancer .  Gemcitabine is known to be the most effective agent in advanced disease as well as an effective agent in patients with resected pancreatic cancer . OBJECTIVE To determine whether fluorouracil or gemcitabine is superior in terms of overall survival as adjuvant treatment following resection of pancreatic cancer . DESIGN , SETTING , AND PATIENTS The European Study Group for Pancreatic Cancer (ESPAC)-3 trial , an open-label , phase 3 , r and omized controlled trial conducted in 159 pancreatic cancer centers in Europe , Australasia , Japan , and Canada . Included in ESPAC-3 version 2 were 1088 patients with pancreatic ductal adenocarcinoma who had undergone cancer resection ; patients were r and omized between July 2000 and January 2007 and underwent at least 2 years of follow-up . INTERVENTIONS Patients received either fluorouracil plus folinic acid ( folinic acid , 20 mg/m(2 ) , intravenous bolus injection , followed by fluorouracil , 425 mg/m(2 ) intravenous bolus injection given 1 - 5 days every 28 days ) ( n = 551 ) or gemcitabine ( 1000 mg/m(2 ) intravenous infusion once a week for 3 of every 4 weeks ) ( n = 537 ) for 6 months . MAIN OUTCOME MEASURES Primary outcome measure was overall survival ; secondary measures were toxicity , progression-free survival , and quality of life . RESULTS Final analysis was carried out on an intention-to-treat basis after a median of 34.2 ( interquartile range , 27.1 - 43.4 ) months ' follow-up after 753 deaths ( 69 % ) . Median survival was 23.0 ( 95 % confidence interval [ CI ] , 21.1 - 25.0 ) months for patients treated with fluorouracil plus folinic acid and 23.6 ( 95 % CI , 21.4 - 26.4 ) months for those treated with gemcitabine ( chi(1)(2 ) = 0.7 ; P = .39 ; hazard ratio , 0.94 [ 95 % CI , 0.81 - 1.08 ] ) . Seventy-seven patients ( 14 % ) receiving fluorouracil plus folinic acid had 97 treatment-related serious adverse events , compared with 40 patients ( 7.5 % ) receiving gemcitabine , who had 52 events ( P < .001 ) . There were no significant differences in either progression-free survival or global quality -of-life scores between the treatment groups . CONCLUSION Compared with the use of fluorouracil plus folinic acid , gemcitabine did not result in improved overall survival in patients with completely resected pancreatic cancer . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00058201
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 .