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)

Autor: Pilar Garrido, Yvonne Summers, Ute von Wangenheim, Michael Flynn, Allan Hackshaw, Manuel Cobo, Siow Ming Lee, Anne-Marie C. Dingemans, Arsene Bienvenu Loembe, David Schnell, Rolf Kaiser, Martin Forster, Tommaso De Pas
Přispěvatelé: RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Pulmonologie, MUMC+: MA Med Staf Spec Longziekten (9)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Oncology
Male
Cancer Research
PHARMACOKINETICS
Indoles
Lung Neoplasms
PACLITAXEL
Deoxycytidine
ANGIOGENESIS
Squamous
chemistry.chemical_compound
0302 clinical medicine
Non-small cell lung cancer
Carcinoma
Non-Small-Cell Lung
Antineoplastic Combined Chemotherapy Protocols
BIBF 1120
Aged
80 and over
Middle Aged
Prognosis
Treatment Outcome
Paclitaxel
LABEL DOSE-ESCALATION
030220 oncology & carcinogenesis
Nintedanib
Female
CLINICAL-PRACTICE GUIDELINES
medicine.drug
Pulmonary and Respiratory Medicine
medicine.medical_specialty
Bevacizumab
Maximum Tolerated Dose
BEVACIZUMAB
CONTROLLED-TRIAL
Disease-Free Survival
03 medical and health sciences
Pharmacokinetics
Internal medicine
medicine
Humans
Adverse effect
Aged
Neoplasm Staging
TRIPLE ANGIOKINASE INHIBITOR
Cisplatin
CARBOPLATIN
business.industry
Gemcitabine
Carboplatin
030104 developmental biology
chemistry
business
Zdroj: Lung Cancer, 120, 27-33. Elsevier Ireland Ltd
ISSN: 0169-5002
Popis: Background 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. Materials and methods 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. Results 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). Conclusions 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.
Databáze: OpenAIRE
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