Oncofocus Test Kit
includes suggestions for Bortezomib
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Velcade (bortezomib) is an antineoplastic agent available for intravenous injection. The proteasome is an enzyme complex that exists in all cells and plays an important role in degrading proteins that control the cell cycle and cellular processes. By blocking the proteasome, Velcade disrupts numerous biologic pathways, including those related to the growth and survival of cancer cells.
Velcade for Injection is indicated for the treatment of multiple myeloma patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy.
The recommended dose of Velcade is 1.3 mg/m2/dose administered as a bolus intravenous injection twice weekly for two weeks followed by a 10-day rest period.
The effectiveness of Velcade is based on response rates. There were no controlled trials demonstrating a clinical benefit, such as an improvement in survival. FDA approval of Velcade was based on an open-label, single-arm, multicenter study of 202 subjects. An IV bolus injection of Velcade 1.3 mg/m2/dose was administered twice weekly for 2 weeks, followed by a 10-day rest period (21 day treatment cycle) for a maximum of 8 treatment cycles. The study employed dose modifications for toxicity. Subjects who experienced a response to Velcade treatment were allowed to continue treatment in an extension study.
Results showed 52 (27.7%) subjects achieved an overall response rate, 5 (2.7%) achieved a complete response, 47 (25%) achieved a partial response and 33 (17.6%) demonstrated a clinical remission. The Kaplan-Meier estimated median duration of response was found to be 365 Days.
Complete Response required 100% disappearance of the original monoclonal protein from blood and urine on at least 2 determinations at least 6 weeks apart by immunofixation, and <5% plasma cells in the 133 bone marrow on at least two determinations for a minimum of six weeks, stable bone disease and calcium.
Partial Response requires ¡Ý50% reduction in serum myeloma protein and ¡Ý 90% reduction of urine myeloma protein on at least 2 occasions for a minimum of at least 6 weeks, stable bone disease and calcium.
Clinical Remission (SWOG) required ¡Ý75% reduction in serum myeloma protein and/or ¡Ý90% reduction of urine myeloma protein on at least 2 occasions for a minimum of at least 6 weeks, stable bone disease and calcium.
Adverse events associated with the use of Oxytrol may include (but are not limited to) the following:
- Appetite decreased
- Peripheral neuropathy
MECHANISM OF ACTION
Based on preclinical studies, bortezomib seems to be cytotoxic to a variety of cancer cell types in vitro. Bortezomib causes a delay in tumor growth in vivo in nonclinical tumor models, including multiple myeloma.
The compound bortezomib is a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome in mammalian cells. The 26S proteasome is a large protein complex that degrades ubiquitinated proteins. These pathway plays an essential role in regulating the intracellular concentration of specific proteins, thereby maintaining balance within cells. Inhibition of the 26S proteasome prevents this targeted proteolysis which can affect multiple signaling cascades within the cell. This disruption of normal mechanisms can lead to cancer cell death.
Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high- dose therapy and haematopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. British Journal of Haematology 1998;102(5):1115-1123.
Elliott PJ, Zollner TM, Boehncke WH.Proteasome inhibition: a new anti-inflammatory strategy.J Mol Med. 2003 Apr;81(4):235-45.
Lenz HJ. Clinical update: proteasome inhibitors in solid tumors.Cancer Treat Rev. 2003 May;29 Suppl 1:41-8.
Salmon SE, Haut A, Bonnet JD, Amare M, Weick JK, Durie BG et al. Alternating combination chemotherapy and levamisole improves survival in multiple myeloma: a Southwest Oncology Group Study. Journal of Clinical Oncology1983;1(8): 453-461.