Open AccessPhase I Study of Nintedanib Incorporating Dynamic Contrast‐Enhanced Magnetic Resonance Imaging in Patients With Advanced Solid Tumors
Author(s) -
Lee Chooi Peng,
Taylor N. Jane,
Attard Gerhardt,
Pacey Simon,
Nathan Paul D.,
Bono Johann S.,
Temple Graham,
Bell Susan,
Stefanic Martin,
Stopfer Peter,
Tang Adrian,
Koh DowMu,
Collins David J.,
d'Arcy James,
Padhani Anwar R.,
Leach Martin O.,
Judson Ian R.,
Rustin Gordon J.
Publication year - 2015
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2014-0250
Subject(s) - medicine , nausea , vomiting , magnetic resonance imaging , asymptomatic , pharmacokinetics , nintedanib , gastroenterology , toxicity , diarrhea , nuclear medicine , radiology , idiopathic pulmonary fibrosis , lung
Background. This open‐label phase I dose‐escalation study investigated the safety, efficacy, pharmacokinetics (PK), and dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) effects of the oral angiokinase inhibitor nintedanib in patients with advanced solid tumors. Methods. Nintedanib was administered once daily continuously, starting at 100 mg and later amended to allow evaluation of 250 mg b.i.d. The primary endpoint was maximum tolerated dose (MTD). DCE‐MRI studies were performed at baseline and on days 2 and 28. Results. Fifty‐one patients received nintedanib 100–450 mg once daily ( n = 40) or 250 mg b.i.d. ( n = 11). Asymptomatic reversible liver enzyme elevations (grade 3) were dose limiting in 2 of 5 patients at 450 mg once daily. At 250 mg b.i.d., 2 of 11 patients experienced dose‐limiting toxicity (grade 3 liver enzyme elevation and gastrointestinal symptoms). Common toxicities included fatigue, diarrhea, nausea, vomiting, and abdominal pain (mainly grade ≤2). Among 45 patients, 22 (49%) achieved stable disease; 7 remained on treatment for >6 months. DCE‐MRI of target lesions revealed effects in some patients at 200 and ≥400 mg once daily. Conclusion. Nintedanib is well tolerated by patients with advanced solid malignancies, with MTD defined as 250 mg b.i.d., and can induce changes in DCE‐MRI. Disease stabilization >6 months was observed in 7 of 51 patients.