PhaseIStudyofNintedanibIncorporatingDynamicContrast-Enhanced Magnetic Resonance Imaging in Patients With Advanced Solid Tumors

Background.This open-label phase I dose-escalation study investigated the safety, efficacy, pharmacokinetics (PK), and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)effectsoftheoralangiokinaseinhibitornintedanib in patients with advanced solid tumors. Methods. Nintedanib was administered once daily continuously,startingat100mgandlateramendedtoallowevaluation of250 mg b.i.d.The primaryendpointwas maximum tolerated dose (MTD). DCE-MRI studies were performed at baseline and on days 2 and 28. Results. Fifty-onepatientsreceivednintedanib100–450mg oncedaily(n540) or250mgb.i.d.(n 511).Asymptomatic reversible liver enzyme elevations (grade 3) were dose limiting in 2 of 5p atients 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 . 6m onths was observed in 7o f 51 patients. The Oncologist 2015;20:368–369 DISCUSSION