TY - JOUR
T1 - A Phase I Study of Concurrent Individualized, Isotoxic Accelerated Radiotherapy and Cisplatin-Vinorelbine-Cetuximab in Patients With Stage III Non-Small-Cell Lung Cancer
AU - Dingemans, Anne-Marie C.
AU - Bootsma, Gerben
AU - van Baardwijk, Angela
AU - Reymen, Bart
AU - Wanders, Rinus
AU - Brans, Boudewijn
AU - Das, Marco
AU - Hochstenbag, Monique
AU - van Belle, Arne
AU - Houben, Ruud
AU - Lambin, Philippe
AU - de Ruysscher, Dirk
PY - 2014/5
Y1 - 2014/5
N2 - Background: In this open-label phase I study, the maximum-tolerated dose of cetuximab with concurrent chemoradiotherapy (C-CRT) in stage III non-small-cell lung cancer together with individualized, isotoxic accelerated radiotherapy (RT) was investigated. Methods: Patients with stage III non-small-cell lung cancer, World Health Organization performance status 0-1, forced expiratory volume in 1 second more than 50%, carbon monoxide diffusing capacity more than 50%, weight loss less than 10%, and no severe comorbidity were enrolled. Patients without progression after one to two cycles of gemcitabine-carboplatin were included and treated with cetuximab 400 mg/kg d7 and 250 mg/kg weekly together with RT and cisplatin (50 mg/m(2) d1, 8; 40 mg/m(2) d22)-vinorelbine for 5 weeks. Vinorelbine was escalated in three steps; (1) 10 mg/m(2) d1, 8 and 8 mg/m(2) d22, 29; (2) 20 mg/m(2) d1, 8 and 8 mg/m(2) d22, 29; (3) 20 mg/m(2) d1, 8; 15 mg/m(2) d22, 29. An individualized prescribed RT dose based on normal tissue dose constraints was applied (e.g., mean lung dose 19 Gy). The primary endpoint was the maximum-tolerated dose 3 months after the end of C-CRT; secondary endpoints were toxicity and metabolic response as assessed by positron emission tomography. Results: Between September 2007 and October 2010, 25 patients (12 men, 13 women, mean age 59 years) were included. The mean RT dose was 62 +/- 6.6 Gy. The vinorelbine dose could be escalated to dose level 3. Twelve of 25 patients experienced greater than or equal to grade 3 toxicity (esophagitis 3, rash 1, diarrhea 1, cough 1, dyspnea 1, vomiting 1, and pulmonary embolism 1). No dose-limiting toxicities were observed. One patient with a complete pathological response in dose level 3 developed a fatal hemoptysis 4 months after RT. Metabolic remissions were observed in 19 of 22 patients. Conclusion: C-CRT with cetuximab and cisplatin-vinorelbine is safe to deliver at full dose. The recommended phase II dose is therefore cetuximab 400 mg/m(2) d7 and 250 mg/m(2) weekly, cisplatin 50 mg/m(2) d1, 8; 40 mg/m(2) d22 and vinorelbine 20 mg/m(2) d1, 8; 15 mg/m(2) d22, 29 for 5 weeks together with RT.
AB - Background: In this open-label phase I study, the maximum-tolerated dose of cetuximab with concurrent chemoradiotherapy (C-CRT) in stage III non-small-cell lung cancer together with individualized, isotoxic accelerated radiotherapy (RT) was investigated. Methods: Patients with stage III non-small-cell lung cancer, World Health Organization performance status 0-1, forced expiratory volume in 1 second more than 50%, carbon monoxide diffusing capacity more than 50%, weight loss less than 10%, and no severe comorbidity were enrolled. Patients without progression after one to two cycles of gemcitabine-carboplatin were included and treated with cetuximab 400 mg/kg d7 and 250 mg/kg weekly together with RT and cisplatin (50 mg/m(2) d1, 8; 40 mg/m(2) d22)-vinorelbine for 5 weeks. Vinorelbine was escalated in three steps; (1) 10 mg/m(2) d1, 8 and 8 mg/m(2) d22, 29; (2) 20 mg/m(2) d1, 8 and 8 mg/m(2) d22, 29; (3) 20 mg/m(2) d1, 8; 15 mg/m(2) d22, 29. An individualized prescribed RT dose based on normal tissue dose constraints was applied (e.g., mean lung dose 19 Gy). The primary endpoint was the maximum-tolerated dose 3 months after the end of C-CRT; secondary endpoints were toxicity and metabolic response as assessed by positron emission tomography. Results: Between September 2007 and October 2010, 25 patients (12 men, 13 women, mean age 59 years) were included. The mean RT dose was 62 +/- 6.6 Gy. The vinorelbine dose could be escalated to dose level 3. Twelve of 25 patients experienced greater than or equal to grade 3 toxicity (esophagitis 3, rash 1, diarrhea 1, cough 1, dyspnea 1, vomiting 1, and pulmonary embolism 1). No dose-limiting toxicities were observed. One patient with a complete pathological response in dose level 3 developed a fatal hemoptysis 4 months after RT. Metabolic remissions were observed in 19 of 22 patients. Conclusion: C-CRT with cetuximab and cisplatin-vinorelbine is safe to deliver at full dose. The recommended phase II dose is therefore cetuximab 400 mg/m(2) d7 and 250 mg/m(2) weekly, cisplatin 50 mg/m(2) d1, 8; 40 mg/m(2) d22 and vinorelbine 20 mg/m(2) d1, 8; 15 mg/m(2) d22, 29 for 5 weeks together with RT.
KW - NSCLC
KW - Concurrent chemoradiotherapy,
KW - Cetuximab
KW - Phase I
U2 - 10.1097/JTO.0000000000000151
DO - 10.1097/JTO.0000000000000151
M3 - Article
C2 - 24722157
SN - 1556-0864
VL - 9
SP - 710
EP - 716
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 5
ER -