SOURCE [1]Novel VELCADE(R) (Bortezomib) for Injection Based Four-Drug Combination Was Well Tolerated In Previously Untreated
Multiple Myeloma Patients Dec. 7, 2008
VELCADE (Bortezomib)
January 3, 2009
December 2008
 Data presented at the 50th Annual Meeting of the American Society of
Hematology (ASH), held December 5-9, 2008 in San Francisco, suggested the combination of four
drugs (VELCADE, dexamethasone, cyclophosphamide and lenalidomide (VcDCR)) was with
previously untreated multiple myeloma (MM). [1]
Velcade (bortezomib) Information

The Food and Drug Administration has approved Velcade to treat a type of cancer called
multiple myeloma. Velcade should only be used in people who have already been treated
with two other types of chemotherapy (drugs used to kill cancer cells), and whose cancer has
still progressed on the most recent therapy.  Velcade is a new type of cancer drug called a
proteasome inhibitor. Proteasomes are enzymes found in cells, and play a role in regulating
cell function and growth. Velcade blocks the activity of proteasomes. This blockade can lead
to death of cancer cells.

On June 23, 2008, the U.S. Food and Drug Administration approved bortezomib for injection
(Velcade, Millennium, Inc. and Johnson and Johnson Pharmaceutical Research and
Development) for the treatment of patients with multiple myeloma. This approval provides
clinical trial data for the use of Velcade as an initial treatment for patients with multiple
myeloma. Velcade was previously approved in 2005 for the treatment of patients with multiple
myeloma who had received at least one prior therapy and in 2003 for the treatment of more
refractory multiple myeloma.

The current approval was based on an international, multicenter, open label, active-control
trial in previously untreated patients with symptomatic multiple myeloma. Patients were
randomized to receive either nine cycles of oral melphalan (M) plus prednisone (P) or MP
plus bortezomib. Patients received M (9 mg/m2 ) plus prednisone (60 mg/m2 ) daily for four
days every 6 weeks or the same MP schedule with bortezomib, 1.3 mg/m2 iv on days 1, 8,
11, 22, 25, 29, and 32 of every 6 week cycle for 4 cycles then once weekly for 4 weeks for 5
cycles. Time- to- progression (TTP) was the primary efficacy endpoint. Overall survival (OS),
progression-free survival (PFS), and response rate (RR) were secondary endpoints. Eligible
patients were age > 65 years. A total of 682 patients were randomized: 338 to receive MP
and 344 to the combination of bortezomib plus MP.  Demographics and baseline disease
characteristics were similar between the two groups.

The trial was stopped following a pre-specified interim analysis showing a statistically
significant improvement in TTP with the addition of bortezomib to MP (median 20.7 months)
compared with MP (median 15 months) [HR: 0.54 (95% CI: 0.42, 0.70), p= 0.000002].  OS,
PFS, and RR also were significantly superior for the bortezomib-MP combination.


The most common adverse reactions (incidence >30%) in clinical studies of bortezomib
include asthenic conditions, diarrhea, nausea, constipation, peripheral neuropathy, vomiting,
pyrexia, thrombocytopenia, psychiatric disorders,
anorexia and decreased appetite,
neutropenia, neuralgia, leukopenia and anemia. Dose adjustment guidelines for hematologic
and neurologic toxicity are detailed in the label (package insert).

Multiple Myeloma

Multiple myeloma is the second most prevalent blood cancer after non-Hodgkin’s lymphoma.
It is a cancer of the plasma cell, an important part of the immune system that produces
antibodies to help fight infection and disease. There are approximately 45,000 people in the
United States living with multiple myeloma and an estimated 14,600 new cases of multiple
myeloma are diagnosed each year.

In the earliest stage of the disease, there may be no symptoms. When symptoms do occur,
patients commonly have bone pain, often in the back or ribs. Patients also may have broken
bones, weakness, tiredness, weight loss, or repeated infections. In the later stages,
symptoms may include nausea, vomiting, constipation, problems with urination, and
weakness or numbness in the legs. These are not sure signs of multiple myeloma; they can
be symptoms of other types of medical problems.


Velcade is distributed and marketed by Millennium Pharmaceuticals, Inc., of Cambridge,


Velcade is a new type of cancer drug called a proteasome inhibitor. Proteasomes are
enzymes found in cells, and play a role in regulating cell function and growth. Velcade blocks
the activity of proteasomes. This blockade can lead to death of cancer cells. The active
ingredient in Velcade is bortezomib. However, proteasomes are found in all cells, and are
necessary for cells to survive and grow. Velcade may kill some good cells along with the
cancer cells, which can lead to side effects.

Reference [1] FDA News May 13, 2003 [2] Velcade (bortezomib) is Approved for Initial Treatment of Patients with Multiple Myeloma
FDA June 23, 2008 [3] Questions and Answers on Velcade FDA

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