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Oncologist. 2015 Apr;20(4):368-9. doi: 10.1634/theoncologist.2014-0250. Epub 2015 Mar 20.

Phase I study of nintedanib incorporating dynamic contrast-enhanced magnetic resonance imaging in patients with advanced solid tumors.

Author information

1
Royal Marsden Hospital and Institute of Cancer Research, Sutton, United Kingdom; chooi.lee@boehringer-ingelheim.com.
2
Mount Vernon Cancer Centre, Northwood, United Kingdom;
3
Royal Marsden Hospital and Institute of Cancer Research, Sutton, United Kingdom;
4
Department of Oncology, The University of Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom;
5
Boehringer Ingelheim Ltd, Bracknell, United Kingdom;
6
Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany;
7
Royal Marsden Hospital and Institute of Cancer Research, Sutton, United Kingdom; Cancer Research UK and Engineering and Physical Sciences Research Council Cancer Imaging Centre, Royal Marsden Hospital and Institute of Cancer Research, Sutton, United Kingdom.

Abstract

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02182206.

PMID:
25795637
PMCID:
PMC4391762
DOI:
10.1634/theoncologist.2014-0250
[Indexed for MEDLINE]
Free PMC Article

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