RT Journal Article
T1 A phase I study of nintedanib combined with cisplatin/gemcitabine as first-line therapy for advanced squamous non-small cell lung cancer (LUME-Lung 3).
A1 Forster, Martin
A1 Hackshaw, Allan
A1 De-Pas, Tommaso
A1 Cobo, Manuel
A1 Garrido, Pilar
A1 Summers, Yvonne
A1 Dingemans, Anne-Marie C
A1 Flynn, Michael
A1 Schnell, David
A1 von-Wangenheim, Ute
A1 Loembe, Arsene-Bienvenu
A1 Kaiser, Rolf
A1 Lee, Siow Ming
K1 Nintedanib
K1 Non-small cell lung cancer
K1 Squamous
AB There are limited treatment options for squamous non-small cell lung cancer (sqNSCLC) and prognosis remains poor. The safety and pharmacokinetics (PK) of nintedanib, a triple angiokinase inhibitor, plus cisplatin/gemcitabine as first-line treatment for advanced sqNSCLC patients, were evaluated. A phase I, dose-escalation study administering drugs in a 21-day cycle: cisplatin (75 mg/m2, Day 1), gemcitabine (1250 mg/m2, Days 1 and 8) and nintedanib (Days 2-7, 9-21) were given for 4-6 cycles, followed by monotherapy until disease progression or adverse events (AEs). Two nintedanib doses were tested, 150 mg twice daily (bid) and 200 mg bid, to determine maximum tolerated dose (MTD) based on occurrence of dose-limiting toxicities (DLTs) during Cycle 1. DLTs were primarily defined as drug-related non-hematologic (Grade ≥3) or hematologic (Grade 4) AEs. Sixteen patients were treated with nintedanib; n = 4 for 150 mg bid, n = 12 for 200 mg bid. No DLTs were observed in Cycle 1; therefore, the MTD was 200 mg bid. In subsequent cycles, two patients had DLTs: renal failure and reduced blood magnesium levels. The most common AEs were gastrointestinal. Three patients discontinued last study medication due to AEs and one had a nintedanib dose reduction. No relevant PK interactions were observed. Five patients had partial responses (31.3%) and eight had stable disease (50.0%); disease control rate was 81.3%. There were three long-term survivors (17-35 months). The safety profile of nintedanib 200 mg bid plus cisplatin/gemcitabine was manageable, with AEs consistent with previous observations. PK data demonstrated no interaction, and preliminary antitumor activity was observed.
PB Elsevier
YR 2018
FD 2018-03-08
LK http://hdl.handle.net/10668/12447
UL http://hdl.handle.net/10668/12447
LA en
NO Forster M, Hackshaw A, De Pas T, Cobo M, Garrido P, Summers Y, et al. A phase I study of nintedanib combined with cisplatin/gemcitabine as first-line therapy for advanced squamous non-small cell lung cancer (LUME-Lung 3). Lung Cancer. 2018 Jun;120:27-33
DS RISalud
RD Apr 17, 2025