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 .
Phase III study of cisplatin, etoposide, and concurrent chest radiation with or without consolidation docetaxel in patients with inoperable stage III non-small-cell lung cancer: the Hoosier Oncology Group and U.S. Oncology.
PURPOSE Concurrent chemoradiotherapy is st and ard treatment for patients with inoperable stage III non-small-cell lung cancer ( NSCLC ) . A phase II study by the Southwest Oncology Group using consolidation docetaxel after cisplatin ( P ) , etoposide ( E ) , and radiation ( XRT ) result ed in a median survival time ( MST ) of 26 months . This r and omized phase III trial evaluated whether consolidation docetaxel was responsible for this improved survival . PATIENTS AND METHODS Eligible patients had stage IIIA or IIIB NSCLC , baseline performance status of 0 to 1 , forced expiratory volume in 1 second > or= 1 L , and less than 5 % weight loss . Patients received P 50 mg/m(2 ) intravenously ( IV ) on days 1 , 8 , 29 , and 36 and E 50 mg/m(2 ) IV on days 1 - 5 and 29 - 33 concurrently with chest XRT to 59.40 Gy . Patients who did not experience progression were r and omly assigned to docetaxel 75 mg/m(2 ) IV every 21 days for three cycles versus observation . The primary end point was to compare overall survival ( Kaplan-Meier analysis ) . RESULTS On the basis of evidence of futility , a data and safety monitoring board recommended early termination after an analysis of the initial 203 patients . Patient characteristics ( n = 203 ) were as follows : 34 % female ; median age , 63 years ; 39.4 % stage IIIA ; and 60.6 % stage IIIB . One hundred forty-seven ( 72.4 % ) of 203 patients were r and omly assigned to docetaxel ( n = 73 ) or observation ( n = 74 ) . Grade 3 to 5 toxicities during docetaxel included febrile neutropenia ( 10.9 % ) and pneumonitis ( 9.6 % ) ; 28.8 % of patients were hospitalized during docetaxel ( v 8.1 % in observation arm ) , and 5.5 % died as a result of docetaxel . The MST for all patients ( n = 203 ) was 21.7 months ; MST was 21.2 months for docetaxel arm compared with 23.2 months for observation arm ( P = .883 ) . CONCLUSION Consolidation docetaxel after PE/XRT results in increased toxicities but does not further improve survival compared with PE/XRT alone in patients with stage III inoperable NSCLC
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 .