Bortezomib is a dipeptide boronic acid drug that inhibits the 20S proteasome. In this paper it is presented as a single-agent therapy for relapsed multiple myeloma.
First-pass extracted concept
bortezomib
Candidate: toolkit item2 source documents10 linked claims
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Aliases
PS-341, Velcade
Extracted Explainers
What the tool is doing
Resources required
The reported regimen uses i.v. bolus dosing at 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day cycle. Clinical use also requires adverse-event monitoring because diarrhea, neuropathy, thrombocytopenia, and other toxicities were common.
The abstract describes body-surface-area-based dosing over repeated 3-week cycles, with response assessment by European Group for Blood and Marrow Transplantation criteria. Dexamethasone could be added for suboptimal response.
What problem it solves
The paper frames bortezomib as an option for patients with multiple myeloma whose disease progressed after at least two prior therapies. It addresses the need for alternatives to conventional cytotoxic chemotherapy in a setting with limited durable remissions.
The paper presents bortezomib as an active option for patients whose myeloma was refractory to conventional chemotherapy and to their most recent therapy.
What it does not solve
The approval summary does not show definitive clinical-benefit endpoints such as improved survival at the time of approval. The paper also documents important toxicity liabilities.
The abstract does not show universal response, and substantial grade 3 and grade 4 adverse events were reported.
Alternatives
The source contrasts bortezomib with conventional cytotoxic chemotherapy, high-dose chemotherapy with stem-cell rescue, glucocorticoids, and thalidomide as other myeloma treatment approaches.
The abstract mentions addition of dexamethasone for suboptimal response. The web research summary identifies the alias PS-341.
Evidence Snippets
Bortezomib (Velcade, formerly known as PS-341) is a dipeptide boronic acid that inhibits the 20S proteasome.
Bortezomib, a boronic acid dipeptide, is a novel proteasome inhibitor... Bortezomib, a member of a new class of anticancer drugs, is active in patients with relapsed multiple myeloma that is refractory to conventional chemotherapy.
Supporting Sources
Linked Claims
In the FDA efficacy analysis population of 188 patients from the open-label Phase II study, bortezomib produced an overall response rate of 28%, with 5 complete responses and 47 partial responses.
The supportive 54-patient dose-finding Phase II study showed a higher response rate at 1.3 mg/m2 than at 1.0 mg/m2, but the study was too small for statistical dose-response comparisons.
Bortezomib inhibits the 20S proteasome.
The FDA granted accelerated marketing approval for bortezomib as a single agent for multiple myeloma in patients who had received at least two prior therapies and had disease progression on the last therapy.
Bortezomib showed notable toxicities, including dose-limiting diarrhea and sensory neurotoxicity in Phase I studies and frequent adverse events such as fatigue, nausea, diarrhea, thrombocytopenia, and peripheral neuropathy in Phase II studies.
In evaluable patients with relapsed refractory myeloma, the response rate to bortezomib was 35 percent.
Quoted textsource-backed
The rate of response to bortezomib was 35 percent
Bortezomib is a novel proteasome inhibitor.
Quoted textsource-backed
Bortezomib, a boronic acid dipeptide, is a novel proteasome inhibitor
Median duration of response with bortezomib treatment in this phase 2 trial was 12 months.
Quoted textsource-backed
with a median duration of response of 12 months
Median overall survival with bortezomib treatment in this phase 2 trial was 16 months.
Quoted textsource-backed
The median overall survival was 16 months
Bortezomib is active in patients with relapsed multiple myeloma refractory to conventional chemotherapy.
Quoted textsource-backed
Bortezomib, a member of a new class of anticancer drugs, is active in patients with relapsed multiple myeloma that is refractory to conventional chemotherapy.