Randomized phase II study of axitinib versus physicians best alternative choice of therapy in patients with recurrent glioblastoma

Autor: Johnny Duerinck, A. Van Binst, M. Le Mercier, Vincent Verschaeve, S. Du Four, Alex Michotte, Bart Neyns, Isabelle Salmon, F. Bouttens, Nicky D'Haene, Hendrik Everaert, F Vandervorst
Přispěvatelé: Neuroprotection & Neuromodulation, Clinical sciences, Laboratory of Molecullar and Cellular Therapy, Faculty of Medicine and Pharmacy, Basic (bio-) Medical Sciences, Radiology, Medical Imaging, Supporting clinical sciences, Laboratory of Molecular and Medical Oncology
Rok vydání: 2015
Předmět:
0301 basic medicine
Oncology
Male
Cancer Research
Axitinib
Phases of clinical research
Angiogenesis Inhibitors
0302 clinical medicine
Lomustine
Clinical endpoint
Brain Neoplasms
Imidazoles
Middle Aged
Protein-Tyrosine Kinases
Bevacizumab
Treatment Outcome
Neurology
030220 oncology & carcinogenesis
Female
Steroids
medicine.drug
Adult
medicine.medical_specialty
Randomized phase II - physicians best alternative choice
Indazoles
Disease-Free Survival
03 medical and health sciences
Young Adult
Fluorodeoxyglucose F18
Internal medicine
medicine
Humans
Adverse effect
Survival rate
Antineoplastic Agents
Alkylating
Protein Kinase Inhibitors
Aged
Temozolomide
business.industry
Surgery
030104 developmental biology
Positron-Emission Tomography
Neurology (clinical)
Neoplasm Recurrence
Local
Radiopharmaceuticals
business
Glioblastoma
Zdroj: Journal of neuro-oncology. 128(1)
ISSN: 1573-7373
Popis: We conducted a randomized, non-comparative, multi center, phase II clinical trial in order to investigate the efficacy of axitinib, an oral small molecule tyrosine kinase inhibitor with high affinity and specificity for the vascular endothelial growth factor receptors, in patients with recurrent glioblastoma following prior treatment with radiation and temozolomide. Forty-four patients were randomly assigned to receive treatment with axitinib (5 mg BID starting dose; N = 22) or “physicians best alternative choice of therapy” that consisted of bevacizumab (N = 20) or lomustine (N = 2). Six-month progression-free survival served as the primary endpoint. The estimated 6-month progression-free survival rate was 34 % (95 % CI 14–54) for patients treated with axitinib and 28 % (95 % CI 8–48) with best alternative treatment; median overall survival was 29 and 17 weeks, respectively. Objective responses according to RANO criteria were documented in 28 % of patients treated with axitinib and 23 % of patients treated with best alternative therapy. A decrease in maximal uptake of 18F-fluoro-ethyl-tyrosine (18F-FET) by the glioblastoma on PET imaging was documented in 85 % of patients at the time of response on axitinib. Corticosteroid treatment could be stopped in four and tapered in seven out of the 15 patients who were treated with steroids at baseline in the axitinib cohort. Most frequent axitinib related grade ≥3 adverse events consisted of fatigue (9 %), diarrhea (9 %), and oral hyperesthesia (4.5 %). We conclude that axitinib has single-agent clinical activity and a manageable toxicity profile in patients with recurrent glioblastoma.
Databáze: OpenAIRE
Externí odkaz: