A Phase I Study of Dasatinib with Concurrent Chemoradiation for Stage III Non-Small Cell Lung Cancer.
OBJECTIVE
Src family kinases (SFKs) are expressed in non-small cell lung cancer (NSCLC) and may be involved in tumor growth and metastases. Inhibition of SFK may also enhance radiation. The purpose of this study was to evaluate if a maximum dose of 100 mg of dasatinib could be safely administered with concurrent chemoradiation and then continued as maintenance for patients with newly diagnosed stage III NSCLC.


METHODS
Patients with stage III locally advanced NSCLC received paclitaxel, 50 mg/m(2)/week, with carboplatin area under the curve (AUC) = 2, weekly for 7 weeks, and concurrent radiotherapy, 64.8 Gy. Three dose levels of dasatinib 50, 70, and 100 mg/day were planned.


RESULTS
11 patients with locally advanced NSCLC were entered. At the 70 mg dose level 1 patient had grade 5 pneumonitis not responsive to therapy, and one patient had reversible grade 3 pneumonitis and grade 3 pericardial effusion. Due to these toxicities the Brown University Oncology Group Data Safety Monitoring Board terminated the study.


CONCLUSIONS
Dasatinib could not be safely combined with concurrent chemoradiation for stage 3 lung cancer due to pneumonitis.
The Brown University Oncology Group, Providence RI, USA.
Humera
H
Khurshid
Thomas
T
Dipetrillo
Thomas
T
Ng
Kalyan
K
Mantripragada
Ariel
A
Birnbaum
David
D
Berz
Kathy
K
Radie-Keane
Kimberly
K
Perez
Maria
M
Constantinou
Denise
D
Luppe
Andrew
A
Schumacher
Kara
K
Leonard
Howard
H
Safran