Proteosome Inhibition with Carfilzomib is Promising Therapeutic Avenue

Implications: Carfilzomib is a nvelo prteosome inhibitor.  Bortezomib, the only proteosome inhibitor that is currently FDA approve, has shown significant activity in myeloma and mantle cell NHL and is being tested in other hematologic malignancies.  If Carfilzomib has improved toxicty and greater efficacy than Bortezomib, it may have a significant role in cancer therapy.

Analysis: Carfilzomib currently is being tested in a phase II trial in myeloma and a phase I trial in lymphoma.  The current report indicates that a phase II trial will be initiated in solid tumors.  Apparently some hints of activity in solid tumors were evident in a phase Ib trial, but those details have not yet been made available.  Giver the multiple tumor types that will be permitted on the phase II trial, including lung cancer, ovarian cancer and renal cell cancer, I am concerned that it will be underpowered to assess potential efficacy in any specific tumor type.  In addition, the activity of Bortezomib in sold tumors has not been impressive to date.