A pilot study of zoledronic acid in the treatment of patients with advanced malignant pleural mesothelioma

Muhammad Omer Jamil, Mary S Jerome, Deborah Miley, Katri S Selander, Francisco Robert Division of Hematology and Oncology, Department of Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA Purpose: Malignant pleural meso...

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Autores principales:	Jamil MO, Jerome MS, Miley D, Selander KS, Robert F
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	bisphosphonates in pleural mesothelioma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/7dc870e0297f40fcb95a1a3fbc1b5f76
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spelling	oai:doaj.org-article:7dc870e0297f40fcb95a1a3fbc1b5f762021-12-02T08:52:08ZA pilot study of zoledronic acid in the treatment of patients with advanced malignant pleural mesothelioma1179-2728https://doaj.org/article/7dc870e0297f40fcb95a1a3fbc1b5f762017-06-01T00:00:00Zhttps://www.dovepress.com/a-pilot-study-of-zoledronic-acid-in-the-treatment-of-patients-with-adv-peer-reviewed-article-LCTThttps://doaj.org/toc/1179-2728Muhammad Omer Jamil, Mary S Jerome, Deborah Miley, Katri S Selander, Francisco Robert Division of Hematology and Oncology, Department of Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA Purpose: Malignant pleural mesothelioma (MPM) is a rare malignancy with a dismal median survival of <12 months with current therapy. Single and combination chemotherapy regimens have shown only modest clinical benefit. In preclinical studies, nitrogen-containing bisphosphonates (zoledronic acid) inhibit growth of mesothelioma cells by different mechanisms: inhibition of mevalonate pathway, inhibition of angiogenesis, activation of apoptosis through caspase activation, and alteration in activity of matrix metalloproteinases, thereby affecting invasiveness of cancer cells.Patients and methods: We investigated the role of zoledronic acid in a pilot, single-arm trial of MPM patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0–2 who had progressed on prior treatments or had not received systemic therapy due to poor PS. Primary end point was composite response rate by modified response evaluation criteria in solid tumors and/or metabolic response by 2-deoxy-2-[fluorine-18]fluoro-d-glucose (18F-FDG) positron emission tomography criteria. Secondary end points were progression-free survival (PFS) and overall survival (OS). Exploratory end points include the effect of zoledronic acid therapy on vascular endothelial growth factor (VEGF), basic fibroblast growth factor, interleukin 8, transforming growth factor beta, mesothelin, and osteopontin levels.Results: Eight male patients (median age of 62 years) with the following clinical characteristics were treated; ECOG PS was 0–2, 75% with epithelioid type, and 62% had prior chemotherapy. Overall composite response rate was 12.5% and the clinical benefit rate (response + stable disease) was 37.5%. Median PFS was 2 months (0.5–21 months) and median OS was 7 months (0.8–28 months). No treatment-related toxicities were observed. Lower VEGF levels were predictive of favorable response and mesothelin levels correlated with disease course.Conclusion: Zoledronic acid shows modest clinical activity without significant toxicity in patients with advanced MPM. Keywords: mesothelioma, treatment, bisphosphonatesJamil MOJerome MSMiley DSelander KSRobert FDove Medical Pressarticlebisphosphonates in pleural mesotheliomaNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENLung Cancer: Targets and Therapy, Vol Volume 8, Pp 39-44 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	bisphosphonates in pleural mesothelioma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	bisphosphonates in pleural mesothelioma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jamil MO Jerome MS Miley D Selander KS Robert F A pilot study of zoledronic acid in the treatment of patients with advanced malignant pleural mesothelioma
description	Muhammad Omer Jamil, Mary S Jerome, Deborah Miley, Katri S Selander, Francisco Robert Division of Hematology and Oncology, Department of Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA Purpose: Malignant pleural mesothelioma (MPM) is a rare malignancy with a dismal median survival of <12 months with current therapy. Single and combination chemotherapy regimens have shown only modest clinical benefit. In preclinical studies, nitrogen-containing bisphosphonates (zoledronic acid) inhibit growth of mesothelioma cells by different mechanisms: inhibition of mevalonate pathway, inhibition of angiogenesis, activation of apoptosis through caspase activation, and alteration in activity of matrix metalloproteinases, thereby affecting invasiveness of cancer cells.Patients and methods: We investigated the role of zoledronic acid in a pilot, single-arm trial of MPM patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0–2 who had progressed on prior treatments or had not received systemic therapy due to poor PS. Primary end point was composite response rate by modified response evaluation criteria in solid tumors and/or metabolic response by 2-deoxy-2-[fluorine-18]fluoro-d-glucose (18F-FDG) positron emission tomography criteria. Secondary end points were progression-free survival (PFS) and overall survival (OS). Exploratory end points include the effect of zoledronic acid therapy on vascular endothelial growth factor (VEGF), basic fibroblast growth factor, interleukin 8, transforming growth factor beta, mesothelin, and osteopontin levels.Results: Eight male patients (median age of 62 years) with the following clinical characteristics were treated; ECOG PS was 0–2, 75% with epithelioid type, and 62% had prior chemotherapy. Overall composite response rate was 12.5% and the clinical benefit rate (response + stable disease) was 37.5%. Median PFS was 2 months (0.5–21 months) and median OS was 7 months (0.8–28 months). No treatment-related toxicities were observed. Lower VEGF levels were predictive of favorable response and mesothelin levels correlated with disease course.Conclusion: Zoledronic acid shows modest clinical activity without significant toxicity in patients with advanced MPM. Keywords: mesothelioma, treatment, bisphosphonates
format	article
author	Jamil MO Jerome MS Miley D Selander KS Robert F
author_facet	Jamil MO Jerome MS Miley D Selander KS Robert F
author_sort	Jamil MO
title	A pilot study of zoledronic acid in the treatment of patients with advanced malignant pleural mesothelioma
title_short	A pilot study of zoledronic acid in the treatment of patients with advanced malignant pleural mesothelioma
title_full	A pilot study of zoledronic acid in the treatment of patients with advanced malignant pleural mesothelioma
title_fullStr	A pilot study of zoledronic acid in the treatment of patients with advanced malignant pleural mesothelioma
title_full_unstemmed	A pilot study of zoledronic acid in the treatment of patients with advanced malignant pleural mesothelioma
title_sort	pilot study of zoledronic acid in the treatment of patients with advanced malignant pleural mesothelioma
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/7dc870e0297f40fcb95a1a3fbc1b5f76
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A pilot study of zoledronic acid in the treatment of patients with advanced malignant pleural mesothelioma

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