�Millennium: The Takeda
Oncology Company proclaimed the publication of results from the 682
patient, randomized, Phase III VISTA(1) trial in this week's edition of the
New England Journal of Medicine. The results showed a significant endurance
benefit and a 30 percent discharge remission (CR) rate with VELCADE,
alkeran and prednisone (VcMP) compared to 4 percent for melaphalan and
prednisone (MP) alone in previously untreated multiple myeloma patients.
Multiple myeloma is the bit most usual blood cancer.
"These data demonstrate that treatment with VELCADE plus melphalan and
prednisone leads to a survival welfare and a high complete remission in
previously untreated patients with multiple myeloma," said Professor Jesus
San Miguel, M.D., Ph.D., Hematology Department Head, University Hospital of
Salamanca and Principal Investigator of the test. "The combination of
VELCADE plus alkeran and liquid Pred is an important modern option for these
patients."
These information originally were presented at the 2007 American Society of
Hematology (ASH) Annual Meeting. Based on these positive visitation results, the
U.S. Food and Drug Administration sanctioned VELCADE for patients with
previously untreated multiple myeloma on June 20, 2008. The Phase III VISTA
trial was conducted by Millennium and its co-development partner Johnson &
Johnson Pharmaceutical Research & Development, L.L.C. in 151 centers
worldwide.
"We are proud to stimulate these information published in such a highly honored
journal," aforementioned Nancy Simonian, M.D., Chief Medical Officer, Millennium.
"We're delighted that previously untreated multiple myeloma patients now
can benefit from this VELCADE based therapy as have patients in the
relapsed and refractory settings since 2003."
(1) VELCADE as Initial Standard Therapy in multiple myeloma: Assessment
with alkeran and prednisone
VISTA Trial Results
Patient responses were evaluated by the stringent European Group for
Blood and Marrow Transplantation (EBMT) criteria:
-- A CR rate of 30 percent in the VcMP arm compared to 4 percent with
MP (p
-- VcMP demonstrated statistical significance in overall survival with
a 39 percent reducing in peril of death (Hazard ratio= 0.61; p=0.008) with
a follow-up of 16.3 months
-- The average treatment continuance was 46 weeks for the VcMP arm compared
to 39 weeks for the control arm and discontinuation due to inauspicious events
was similar in both arms
Patients in the VcMP arm standard VELCADE at 1.3 mg/m2 twice weekly in
weeks unmatchable, two, four-spot and basketball team for four-spot six-week cycles (eight doses per
cycle), followed by once weekly on weeks one, two, four and five for up to
five six-week cycles (foursome doses per cycle) in combination with melphalan
at 9 mg/m2 and orasone at 60 mg/m2 once daily on days 1 through 4 of
each cycle for up to nine six-week cycles. For both groups, treatment
continued for a maximum of 54 weeks.
"The tolerability of VcMP also was encouraging and side personal effects were
in general manageable with appropriate supportive care and dose reduction as
needed," commented Paul Richardson, M.D., Clinical Director of the Jerome
Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute and Senior
Investigator on the study.
The safety profile of VELCADE in combination with MP is consistent with
the known safety profiles of both VELCADE and MP. In VISTA, the most
ordinarily reported adverse events for VELCADE in combination with MP vs MP,
respectively, were thrombocytopenia (52% vs 47%), neutropenia (49% vs 46%),
nausea (48% vs 28%), peripheral neuropathy (47% vs 5%), diarrhea (46% vs
17%), anemia (43% vs 55%), constipation (37% vs 16%), neuralgia (36% vs
1%), leukopenia (33% vs 30%), vomiting (33% vs 16%), pyrexia (29% vs 19%),
fatigue (29% vs 26%), lymphopenia (24% vs 17%), anorexia (23% vs 10%),
asthenia (21% vs 18%), cough (21% vs 13%), insomnia (20% vs 13%), edema
peripheral (20% vs 10%), rash (19% vs 7%), back pain (17% vs 18%),
pneumonia (16% vs 11%), dizziness (16% vs 11%), dyspnea (15% vs 13%),
headache (14% vs 10%), pain in extremity (14% vs 9%), abdominal painfulness (14%
vs 7%), paraesthesia (13% vs 4%), herpes virus zoster (13% vs 4%), bronchitis (13%
vs 8%), hypokalemia (13% vs 7%), hypertension (13% vs 7%), abdominal pain sensation
upper (12% vs 9%), hypotension (12% vs 3%), dyspepsia (11% vs 7%),
nasopharyngitis (11% vs 8%), bone pain sensation (11% vs 10%), arthralgia (11% vs
15%) and pruritus (10% vs 5%).
Important Safety Information
In the U.S., VELCADE is indicated for the treatment of patients with
multiple myeloma. VELCADE as well is indicated for the treatment of patients
with mantle cell lymphoma world Health Organization have received at least one prior therapy.
VELCADE is contraindicated in patients with hypersensitivity to bortezomib,
boron or mannitol. VELCADE should be administered under the supervising of
a physician experienced in the use of antineoplastic therapy.
Risks associated with VELCADE therapy include new or worsening
peripheral neuropathy, hypotension throughout therapy, cardiac and
pulmonary disorders, reversible nates leukoencephalopathy syndrome,
gastrointestinal adverse events, thrombopenia, neutropenia, tumour lysis
syndrome and liverwort events. Women of childbirth potential should avoid
seemly pregnant spell being treated with VELCADE. Nursing mothers are
advised not to breastfeed patch receiving VELCADE. Cases of severe sensorial
and motor peripheral neuropathy have been reported. The long-term final result
of peripheral neuropathy has not been studied in mantle jail cell lymphoma.
Acute development or exacerbation of congestive heart failure, and new
onset of reduced left ventricular ejection fraction has been reported,
including reports in patients with no risk factors for decreased left
ventricular forcing out fraction. There have been reports of acute pervade
infiltrative pneumonic disease of unknown etiology such as pneumonitis,
interstitial pneumonia, lung infiltration and Acute Respiratory Distress
Syndrome in patients receiving VELCADE. Some of these events have been
fatal. There have been reports of Reversible Posterior Leukoencephalopathy
Syndrome (RPLS) in patients receiving VELCADE. RPLS is a rare, reversible,
neurological disorderliness which john present with seizure, high blood pressure,
headache, slackness, confusion, blindness, and other visual and neurological
disturbances. VELCADE is associated with thrombocytopenia and neutropenia.
There have been reports of gastrointestinal and intracerebral hemorrhage in
association with VELCADE. Transfusions crataegus laevigata be considered. Complete blood
counts (CBC) should be frequently monitored during treatment with VELCADE.
Cases of acute liver failure get been reported in patients receiving
multiple concomitant medications and with serious underlying medical
conditions. Patients world Health Organization are concomitantly receiving VELCADE and drugs that
ar inhibitors or inducers of cytochrome P450 3A4 should be tight
monitored for either toxicities or reduced efficacy. Patients on oral
antidiabetic medicament while receiving VELCADE should check blood sugar
levels frequently.
Adverse Reaction Data
Safety data from Phase II and III studies of single-agent VELCADE 1.3
mg/m2/dose twice weekly for 2 weeks followed by a 10-day rest geological period in
1163 patients with previously treated multiple myeloma (N=1008, non
including the Phase III, VELCADE summation DOXIL(R) [doxorubicin HCl liposome
injection] study) and antecedently treated mantle cell lymphoma (N=155) were
integrated and tabulated. In these studies, the safety profile of VELCADE
was similar in patients with multiple myeloma and curtain cell lymphoma.
In the integrated analysis, the most commonly reported adverse events
were asthenic conditions (including fatigue, uneasiness and failing) (64%),
nausea (55%), diarrhea (52%), stultification (41%), peripheral neuropathy NEC
(including peripheral sensory neuropathy and peripheral neuropathy
aggravated) (39%), thrombocytopenia and appetite decreased (including
anorexia) (each 36%), fever (34%), disgorgement (33%), anaemia (29%), oedema
(23%), worry, paresthesia and dysesthesia and headache (each 22%),
dyspnoea (21%), coughing and insomnia (each 20%), rash (18%), arthralgia (17%),
neutropenia and dizziness (excluding vertigo) (each 17%), pain in tree branch and
abdominal muscle pain (each 15%), os pain (14%), back painfulness and hypotension (each
13%), herpes herpes zoster, nasopharyngitis, upper respiratory tract infection,
myalgia and pneumonia (each 12%), muscle cramps (11%), and dehydration and
anxiety (each 10%). Twenty percent (20%) of patients experienced at least 1
episode of greater than or touch to Grade 4 toxicity, most commonly
thrombocytopenia (5%) and neutropenia (3%). A total of 50% of patients
experienced serious contrary events (SAEs) during the studies. The most
ordinarily reported SAEs included pneumonia (7%), febricity (6%), looseness of the bowels
(5%), vomit (4%), and nausea, desiccation, dyspnea and thrombocytopenia
(each 3%).
About Multiple Myeloma
Multiple myeloma is the second most mutual hematological malignancy.
Between 2001 - 2005, the average age of diagnosis was 70
