Perifosine Plus Bortezomib and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma Previously Treated With Bortezomib: Results of a Multicenter Phase I/II Trial
| Autor: | L. Gardner, Amrita Krishnan, Robert L. Schlossman, Jeff Allerton, Jacob P. Laubach, David Irwin, Sagar Lonial, Kathleen Colson, John J. Densmore, Noopur Raje, Peter Sportelli, Jeff Zonder, Enrique Poradosu, Jeff Wolf, Andrzej Jakubowiak, Kenneth C. Anderson, Michael Bar, Paul G. Richardson, Irene M. Ghobrial, Teru Hideshima, Thomas Martin, Nikhil C. Munshi |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Oncology Cancer Research medicine.medical_specialty Phosphorylcholine Phases of clinical research Dexamethasone Disease-Free Survival Bortezomib chemistry.chemical_compound Refractory Recurrence immune system diseases hemic and lymphatic diseases Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans In patient Multiple myeloma Aged Aged 80 and over business.industry Middle Aged Perifosine medicine.disease Boronic Acids Clinical trial chemistry Pyrazines Female Multiple Myeloma business medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 29:4243-4249 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | Purpose Novel agents have improved patient outcome in relapsed or relapsed/refractory multiple myeloma (MM). Preclinical data show that the novel signal transduction modulator, perifosine, enhances the cytotoxicity of dexamethasone and bortezomib. Clinical data suggest that perifosine in combination with dexamethasone has activity in relapsed or relapsed/refractory MM. Patients and Methods In a phase I/II study, perifosine in combination with bortezomib with or without dexamethasone was prospectively evaluated in 84 patients with relapsed or relapsed/refractory MM. All were heavily pretreated and bortezomib exposed; 73% were refractory to bortezomib, and 51% were refractory to bortezomib and dexamethasone. The dose selected for the phase II study was perifosine 50 mg/d plus bortezomib 1.3 mg/m2, with the addition of low-dose dexamethasone at 20 mg if progression occurred on perifosine plus bortezomib alone. Results An overall response rate (ORR; defined as minimal response or better) of 41% was demonstrated with this combination in 73 evaluable patients, including an ORR of 65% in bortezomib-relapsed patients and 32% in bortezomib-refractory patients. Therapy was generally well tolerated; toxicities, including gastrointestinal adverse effects and fatigue, proved manageable. No treatment-related mortality was seen. Median progression-free survival was 6.4 months, with a median overall survival of 25 months (22.5 months in bortezomib-refractory patients). Conclusion Perifosine–bortezomib ± dexamethasone demonstrated encouraging activity in heavily pretreated bortezomib-exposed patients with advanced MM. A phase III trial is underway comparing perifosine–bortezomib plus dexamethasone with bortezomib–dexamethasone in patients with relapsed/refractory MM previously treated with bortezomib. |
| Databáze: | OpenAIRE |
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