Chugh, R., Wathen, J. K., Maki, R. G., Benjamin, R. S., Patel, S. R., Meyers, P. A., Priebat, D. A., Reinke, D. K., Thomas, D. G., Keohan, M. L., Samuels, B. L., Baker, L. H. (July 2009) Phase II multicenter trial of imatinib in 10 histologic subtypes of sarcoma using a bayesian hierarchical statistical model. J Clin Oncol, 27 (19). pp. 3148-53. ISSN 1527-7755 (Electronic)0732-183X (Linking)
Abstract
PURPOSE The purpose of this trial was to assess the efficacy of imatinib in patients with one of 10 different subtypes of advanced sarcoma. PATIENTS AND METHODS Eligible patients were treated daily with imatinib dosed at 300 mg twice a day (for body-surface area > or = 1.5 m(2)). The primary end point was response (clinical benefit response [CBR]), defined as complete (CR) or partial response (PR) at 2 months, or stable disease, CR, or PR at 4 months. Rules for early termination within each disease type were based on a Bayesian hierarchical probability model (BHM) accounting for correlation of the responses of the 10 subtypes. Available tissue samples were analyzed for molecules within the KIT/platelet-derived growth factor receptor (PDGFR) signal transduction pathway. Results One hundred eighty-five assessable patients with one of 10 subtypes of sarcoma were treated. One CR and three PRs were achieved. A CBR was achieved in 28 patients treated overall and by subtype: two angiosarcomas (n = 16), 0 Ewing (n = 13), one fibrosarcoma (n = 12), six leiomyosarcomas (n = 29), seven liposarcomas (n = 31), three malignant fibrous histiocytomas (n = 30), five osteosarcomas (n = 27), one malignant peripheral-nerve sheath tumor (n = 7), 0 rhabdomyosarcoma (n = 2), and three synovial sarcomas (n = 22). Variable expression and mutations within the KIT/PDGFR pathway were observed. CONCLUSION This is the first phase II study of a new agent in sarcoma to include sufficient patients with each of the common histologic subtypes to permit generalizable conclusions. The BHM is an effective method for studying rare diseases and their subtypes, when it is reasonable to assume that their response rates are exchangeable. Although rare dramatic responses were seen, imatinib is not an active agent in advanced sarcoma in these subtypes.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Adolescent Adult Aged Aged, 80 and over Antineoplastic Agents/*therapeutic use Bayes Theorem Benzamides Disease-Free Survival Female Humans Imatinib Mesylate Immunohistochemistry Male Middle Aged Piperazines/*therapeutic use Polymerase Chain Reaction Pyrimidines/*therapeutic use Sarcoma/*drug therapy/*pathology Treatment Outcome Young Adult |
| Subjects: | diseases & disorders > cancer > drugs and therapies diseases & disorders > cancer > cancer types > sarcoma |
| CSHL Authors: | |
| Communities: | CSHL labs > Maki lab |
| Depositing User: | Matt Covey |
| Date: | 1 July 2009 |
| Date Deposited: | 26 Oct 2016 15:27 |
| Last Modified: | 26 Oct 2016 15:27 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/33694 |
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