Phase II clinical trial of first or second-line treatment with bortezomib in patients with malignant pleural mesothelioma

Fennell, D. A., McDowell, C., Busacca, S., Webb, G., Moulton, B., Cakana, A., O'Byrne, Kenneth J., Meerbeeck, J. V., Donnellan, P., McCaffrey, J., & Baas, P. (2012) Phase II clinical trial of first or second-line treatment with bortezomib in patients with malignant pleural mesothelioma. Journal of Thoracic Oncology, 7(9), pp. 1466-1470.

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Based on promising preclinical efficacy of bortezomib in mesothelioma, a single-arm phase II trial (Ireland Cooperative Oncology Research Group 05-10 study), with Simon's two-stage design, was undertaken to assess efficacy of bortezomib monotherapy in the first-line (poor performance status) and second-line settings. The Bcl-2 homology domain 3-only protein Noxa has been implicated as a key inducer of apoptosis by bortezomib. Thus, in a biomarker research substudy, we hypothesized that deficiency in Noxa expression might correlate with resistance. In the second-line setting, 23 patients were enrolled. Partial response was confirmed in one patient (4.8%) who received four cycles of bortezomib. One patient had stable disease; however, progression occurred in the majority of patients within the first two cycles. Median progression-free survival and overall survival were 2.1 and 5.8 months, respectively. In the first-line setting, ten patients were accrued, and there was no evidence of objective response. In the tumor analysis, expression of Noxa was seen in all biopsies. Bortezomib monotherapy exhibits insufficient activity to warrant further investigation in unselected patients with mesothelioma. © 2012 by the International Association for the Study of Lung.

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23 citations in Scopus
20 citations in Web of Science®
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ID Code: 65051
Item Type: Journal Article
Refereed: No
Additional URLs:
Keywords: Bortezomib, Chemotherapy, First-line, Mesothelioma, Second-line, protein bcl 2, protein Noxa, aged, apoptosis, article, cancer chemotherapy, cancer growth, cancer patient, cancer survival, clinical article, congestive heart failure, drug dose reduction, drug efficacy, drug withdrawal, female, heart atrium fibrillation, human, human tissue, male, multiple cycle treatment, overall survival, patient selection, phase 2 clinical trial, pleura biopsy, pleura mesothelioma, priority journal, progression free survival, protein domain, treatment duration, treatment response, Boronic Acids, Disease Progression, Follow-Up Studies, Humans, Immunoenzyme Techniques, Middle Aged, Neoplasm Staging, Pleural Neoplasms, Prognosis, Proto-Oncogene Proteins c-bcl-2, Pyrazines, Survival Rate
DOI: 10.1097/JTO.0b013e318260dfb9
ISSN: 1556-0864
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2012 Lippincott Williams & Wilkins
Deposited On: 03 Dec 2013 07:19
Last Modified: 18 Dec 2013 05:13

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