Phase II Clinical Trial of First or Second-Line Treatment with Bortezomib in Patients with Malignant Pleural Mesothelioma.

Fennell DA, McDowell C, Busacca S, Webb G, Moulton B, Cakana A, O'Byrne KJ, Meerbeeck JV, Donnellan P, McCaffrey J, Baas P.

Source

*Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, United Kingdom; †Department of Clinical Oncology, The Royal Hospitals, Belfast, United Kingdom; ‡ICORG, the All-Ireland Cooperative Oncology Research Group, Dublin, Ireland; §Johnson & Johnson Research & Development, High Wycombe, United Kingdom; ║Department of Medical Oncology, St James' Hospital, Dublin, Ireland; ¶Department of Thoracic Oncology, University Hospital, Ghent, Belgium; #Department of Medical Oncology, Galway University Hospital, Galway, Ireland; **Department of Medical Oncology, Mater Misericordiae University Hospital & Mater Private Hospital, Dublin, Ireland; and ††Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Abstract

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.

TimAllenMDJD

Friday, August 17, 2012