Phase II study of pazopanib in combination with paclitaxel in patients with metastatic melanoma

Autor: Katherine Osann, John P. Fruehauf, Monica El-Masry, Basmina Parmakhtiar, Maki Yamamoto, James G. Jakowatz
Rok vydání: 2018
Předmět:
Male
Cancer Research
Phases of clinical research
Kaplan-Meier Estimate
Toxicology
Tyrosine-kinase inhibitor
chemistry.chemical_compound
0302 clinical medicine
Antineoplastic Combined Chemotherapy Protocols
Medicine
Pharmacology (medical)
030212 general & internal medicine
Receptor
Melanoma
Aged
80 and over
Sulfonamides
biology
Middle Aged
Progression-Free Survival
Vascular endothelial growth factor
Oncology
Paclitaxel
Antiangiogenic agent
030220 oncology & carcinogenesis
Female
Platelet-derived growth factor receptor
medicine.drug
Adult
Indazoles
medicine.drug_class
Metastatic melanoma
BRAF
Pazopanib
03 medical and health sciences
Growth factor receptor
Humans
Aged
Neoplasm Staging
Pharmacology
business.industry
Metronomic paclitaxel
Pyrimidines
chemistry
Clinical Trial Report
Administration
Metronomic
biology.protein
Cancer research
business
Zdroj: Cancer Chemotherapy and Pharmacology
Fruehauf, JP; El-Masry, M; Osann, K; Parmakhtiar, B; Yamamoto, M; & Jakowatz, JG. (2018). Phase II study of pazopanib in combination with paclitaxel in patients with metastatic melanoma. CANCER CHEMOTHERAPY AND PHARMACOLOGY, 82(2), 353-360. doi: 10.1007/s00280-018-3624-6. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/5xn2f71m
ISSN: 1432-0843
Popis: Purpose This phase II study evaluated the safety and clinical activity of pazopanib, a potent and mutlitargeted tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptors (VEGFRs)-1, -2 and -3, platelet-derived growth factor receptor (PDGFR)-α and β, and cKit, in combination with metronomic paclitaxel in patients with metastatic melanoma. Experimental design Sixty chemotherapy-naive patients received pazopanib at a starting dose of 800 mg daily in combination with metronomic dosing of paclitaxel 80 mg/m2 weekly thrice every 4 weeks. The primary endpoint was 6-month progression-free survival (PFS) rate, while secondary endpoints included 1-year overall survival rate, RECIST response rates, progression-free survival rates and median overall survival. Prior BRAF-targeted therapy or checkpoint inhibitors were permitted. Results The 6-month PFS rate was 68%, with a 1-year OS rate of 48%. Objective response rate was 37% comprising one complete and 20 partial responses. Stable disease at 8 weeks was noted in 32 patients (55%) with an overall clinical benefit rate of 93%. Six-month median progression-free survival was 8 months and median OS was 12.7 months. The most frequently (> 15%) reported non-hematologic, treatment-related adverse events were fatigue, diarrhea, hypertension, transaminitis and peripheral neuropathy. Treatment-related non-fatal bowel perforation, a known class effect, occurred in one patient. No significant association was noted between plasma levels of pazopanib and response. Conclusions The combination of pazopanib and metronomic paclitaxel was well-tolerated, demonstrating significant activity in metastatic melanoma. Further evaluation of this combination is warranted.
Databáze: OpenAIRE
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