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Details

Stereochemistry ABSOLUTE
Molecular Formula C57H69B3N12O9
Molecular Weight 1098.666
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BORTEZOMIB BORONIC ANHYDRIDE

SMILES

CC(C)C[C@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)C2=NC=CN=C2)B3OB(OB(O3)[C@H](CC(C)C)NC(=O)[C@H](CC4=CC=CC=C4)NC(=O)C5=NC=CN=C5)[C@H](CC(C)C)NC(=O)[C@H](CC6=CC=CC=C6)NC(=O)C7=NC=CN=C7

InChI

InChIKey=YVBHFXUJMLXLKP-INZJBPCBSA-N
InChI=1S/C57H69B3N12O9/c1-37(2)28-49(70-52(73)43(31-40-16-10-7-11-17-40)67-55(76)46-34-61-22-25-64-46)58-79-59(50(29-38(3)4)71-53(74)44(32-41-18-12-8-13-19-41)68-56(77)47-35-62-23-26-65-47)81-60(80-58)51(30-39(5)6)72-54(75)45(33-42-20-14-9-15-21-42)69-57(78)48-36-63-24-27-66-48/h7-27,34-39,43-45,49-51H,28-33H2,1-6H3,(H,67,76)(H,68,77)(H,69,78)(H,70,73)(H,71,74)(H,72,75)/t43-,44-,45-,49-,50-,51-/m0/s1

HIDE SMILES / InChI

Molecular Formula C57H69B3N12O9
Molecular Weight 1098.666
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 6 / 6
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/11854543 http://www.drugbank.ca/drugs/DB00188 https://www.drugs.com/mtm/bortezomib.html https://en.wikipedia.org/wiki/Bortezomib

Bortezomib is the therapeutic proteasome inhibitor. First, which is tested in humans. The boron atom in bortezomib binds the catalytic site of the 26S proteasome with high affinity and specificity. Bortezomib is approved in the U.S. for treating relapsed multiple myeloma and mantle cell lymphoma. The 26S proteasome degrades various proteins critical to cancer cell survival, such as cyclins, tumor suppressors, BCL-2, and cyclin-dependent kinase inhibitors. Inhibition of these degradations sensitizes cells to apoptosis. Bortezomib is a potent inhibitor of 26S proteasome, which sensitizes activity in dividing multiple myeloma and leukemic cells, thus inducing apoptosis. Most commonly reported adverse reactions (incidence ≥30%) in clinical studies include asthenic conditions, diarrhea, nausea, constipation, peripheral neuropathy, vomiting, pyrexia, thrombocytopenia, psychiatric disorders, anorexia and decreased appetite, neutropenia, neuralgia, leukopenia and anemia. Co-administration of ketoconazole, a potent CYP3A inhibitor, increased the exposure of bortezomib. Co-administration of melphalan-prednisone increased the exposure of bortezomib. However, this increase is unlikely to be clinically relevant.

CNS Activity

Curator's Comment: Based on animal studies, the penetration of bortezomib through the blood-brain barrier appears to be limited, if any and the relevance to humans is unknown. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000539/WC500048467.pdf http://meeting.ascopubs.org/cgi/content/short/24/18_suppl/12036 https://www.ncbi.nlm.nih.gov/pubmed/26792401

Originator

Curator's Comment: ProScript was acquired in 1999 by Millennium Pharmaceuticals Inc., which eventually funded studies of PS-341. http://archive.boston.com/business/healthcare/articles/2007/05/06/the_velcade_story/

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.6 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
VELCADE

Approved Use

VELCADE is a proteasome inhibitor indicated for: treatment of patients with multiple myeloma (1.1) treatment of patients with mantle cell lymphoma (1.2) 1.1 Multiple Myeloma VELCADE® (bortezomib) is indicated for the treatment of patients with multiple myeloma. 1.2 Mantle Cell Lymphoma VELCADE is indicated for the treatment of patients with mantle cell lymphoma.

Launch Date

2003
Primary
VELCADE

Approved Use

VELCADE is a proteasome inhibitor indicated for: treatment of patients with multiple myeloma (1.1) treatment of patients with mantle cell lymphoma (1.2) 1.1 Multiple Myeloma VELCADE® (bortezomib) is indicated for the treatment of patients with multiple myeloma. 1.2 Mantle Cell Lymphoma VELCADE is indicated for the treatment of patients with mantle cell lymphoma.

Launch Date

2003
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
106.2 ng/mL
1 mg/m² 1 times / 4 days multiple, oral
dose: 1 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BORTEZOMIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
127.02 ng/mL
1.3 mg/m^2 1 times / 4 day steady, intravenous
dose: 1.3 mg/m^2
route of administration: intravenous
experiment type: steady
co-administered:
BORTEZOMIB plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
76.43 ng/mL
1.3 mg/m^2 single, intravenous
dose: 1.3 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
BORTEZOMIB plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
82.8 ng × h/mL
1 mg/m² 1 times / 4 days multiple, oral
dose: 1 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BORTEZOMIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
190.39 ng*h/mL
1.3 mg/m^2 1 times / 4 day steady, intravenous
dose: 1.3 mg/m^2
route of administration: intravenous
experiment type: steady
co-administered:
BORTEZOMIB plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
51.86 ng*h/mL
1.3 mg/m^2 single, intravenous
dose: 1.3 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
BORTEZOMIB plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
106.99 ng*h/mL
1.3 mg/m^2 single, intravenous
dose: 1.3 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
BORTEZOMIB plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
349.62 ng*h/mL
1.3 mg/m^2 1 times / 4 day steady, intravenous
dose: 1.3 mg/m^2
route of administration: intravenous
experiment type: steady
co-administered:
BORTEZOMIB plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
78.9 h
1 mg/m² 1 times / 4 days multiple, oral
dose: 1 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BORTEZOMIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
0.08 h
1.3 mg/m^2 single, intravenous
dose: 1.3 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
BORTEZOMIB plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
51.55 h
1.3 mg/m^2 1 times / 4 day steady, intravenous
dose: 1.3 mg/m^2
route of administration: intravenous
experiment type: steady
co-administered:
BORTEZOMIB plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
17%
BORTEZOMIB plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1.9 mg/m2 2 times / week steady, intravenous
Highest studied dose
Dose: 1.9 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.9 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
DLT: Thrombocytopenia, Sensory neuropathy...
Other AEs: Diarrhea, Hypotension...
Dose limiting toxicities:
Thrombocytopenia (grade 3, 1 patient)
Sensory neuropathy (grade 3, 1 patient)
Fatigue (grade 3, 1 patient)
Other AEs:
Diarrhea (grade 3-4, 1 patient)
Hypotension (grade 3-4, 1 patient)
Hypoxia (grade 3-4, 1 patient)
Infection (grade 3-4, 1 patient)
Acidosis (grade 3-4)
CPK increased (grade 3-4)
Blood bicarbonate low (grade 3-4)
Hypokalemia (grade 3-4)
Alanine aminotransferase increase (grade 3-4)
Sources:
1.7 mg/m2 2 times / week steady, intravenous
MTD
Dose: 1.7 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.7 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Other AEs: Thrombocytopenia, Sensory neuropathy...
Other AEs:
Thrombocytopenia (all grades, 5 patients)
Sensory neuropathy (grade 3, 3 patients)
Abdominal pain (grade 3, 1 patient)
Constipation (grade 3, 1 patient)
Depressed level of consciousness (grade 3, 1 patient)
Fatigue (grade 3, 1 patient)
Headache (grade 3, 1 patient)
Pain (grade 3, 1 patient)
Hypokalemia (grade 3, 1 patient)
Sources:
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Other AEs: Thrombocytopenia, Thrombocytopenia...
Other AEs:
Thrombocytopenia (grade 3, 18%)
Thrombocytopenia (grade 4-5, 17%)
Neutropenia (grade 3, 30%)
Neutropenia (grade 4-5, 10%)
Anemia (grade 3, 12%)
Anemia (grade 4-5, 1%)
Leukopenia (grade 3, 19%)
Leukopenia (grade 4-5, 2%)
Lymphopenia (grade 3, 14%)
Lymphopenia (grade 4-5, 5%)
Nausea (grade 3, 3%)
Diarrhea (grade 3, 6%)
Diarrhea (grade 4-5, 1%)
Vomiting (grade 3, 4%)
Constipation (grade 3, 1%)
Abdominal pain upper (grade 3, <1%)
Peripheral neuropathy (grade 3, 12%)
Peripheral neuropathy (grade 4-5, 1%)
Neuralgia (grade 3, 8%)
Neuralgia (grade 4-5, 1%)
Paresthesia (grade 3, 2%)
Fatigue (grade 3, 6%)
Fatigue (grade 4-5, 1%)
Asthenia (grade 3, 5%)
Pyrexia (grade 3, 1%)
Herpes zoster (grade 3, 3%)
Anorexia (grade 3, 2%)
Rash (grade 3, 1%)
Insomnia (grade 3, < 1%)
Sources:
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: multiple myeloma |mantle cell lymphoma
Sex: M+F
Population Size: 331
Sources:
Disc. AE: Hypotension, Pyrexia...
AEs leading to
discontinuation/dose reduction:
Hypotension (1%)
Pyrexia (< 1%)
Weakness (< 1%)
Asthenia (< 1%)
Sources:
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Disc. AE: Peripheral neuropathy, Cardiogenic shock...
Other AEs: Diarrhea, Dehydration...
AEs leading to
discontinuation/dose reduction:
Peripheral neuropathy (8%)
Cardiogenic shock (grade 5, 1 patient)
Respiratory insufficiency (grade 5, 1 patient)
Congestive heart failure (grade 5, 1 patient)
Cardiac arrest (grade 5, 1 patient)
Fatigue (2%)
Thrombocytopenia (2%)
Diarrhea (2%)
Other AEs:
Diarrhea (serious, 3%)
Dehydration (serious, 2%)
Herpes zoster (serious, 2%)
Pyrexia (serious, 2%)
Nausea (serious, 2%)
Vomiting (serious, 2%)
Dyspnea (serious, 2%)
Thrombocytopenia (serious, 2%)
Constipation (grade 3, 2%)
Anorexia (grade 3, 2%)
Paresthesia (grade 3, 2%)
Anaemia NOS (grade 3, 6%)
Anaemia NOS (grade 4, <1%)
Headache (grade 3, <1%)
Neutropenia (grade 3, 11%)
Neutropenia (grade 4, 2%)
Rash NOS (grade 3, <1%)
Abdominal pain (grade 3, 2%)
Weakness (grade 3, 3%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Fatigue grade 3, 1 patient
DLT
1.9 mg/m2 2 times / week steady, intravenous
Highest studied dose
Dose: 1.9 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.9 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Sensory neuropathy grade 3, 1 patient
DLT
1.9 mg/m2 2 times / week steady, intravenous
Highest studied dose
Dose: 1.9 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.9 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Thrombocytopenia grade 3, 1 patient
DLT
1.9 mg/m2 2 times / week steady, intravenous
Highest studied dose
Dose: 1.9 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.9 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Acidosis grade 3-4
1.9 mg/m2 2 times / week steady, intravenous
Highest studied dose
Dose: 1.9 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.9 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Alanine aminotransferase increase grade 3-4
1.9 mg/m2 2 times / week steady, intravenous
Highest studied dose
Dose: 1.9 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.9 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Blood bicarbonate low grade 3-4
1.9 mg/m2 2 times / week steady, intravenous
Highest studied dose
Dose: 1.9 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.9 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
CPK increased grade 3-4
1.9 mg/m2 2 times / week steady, intravenous
Highest studied dose
Dose: 1.9 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.9 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Hypokalemia grade 3-4
1.9 mg/m2 2 times / week steady, intravenous
Highest studied dose
Dose: 1.9 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.9 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Diarrhea grade 3-4, 1 patient
1.9 mg/m2 2 times / week steady, intravenous
Highest studied dose
Dose: 1.9 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.9 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Hypotension grade 3-4, 1 patient
1.9 mg/m2 2 times / week steady, intravenous
Highest studied dose
Dose: 1.9 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.9 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Hypoxia grade 3-4, 1 patient
1.9 mg/m2 2 times / week steady, intravenous
Highest studied dose
Dose: 1.9 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.9 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Infection grade 3-4, 1 patient
1.9 mg/m2 2 times / week steady, intravenous
Highest studied dose
Dose: 1.9 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.9 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Thrombocytopenia all grades, 5 patients
1.7 mg/m2 2 times / week steady, intravenous
MTD
Dose: 1.7 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.7 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Abdominal pain grade 3, 1 patient
1.7 mg/m2 2 times / week steady, intravenous
MTD
Dose: 1.7 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.7 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Constipation grade 3, 1 patient
1.7 mg/m2 2 times / week steady, intravenous
MTD
Dose: 1.7 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.7 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Depressed level of consciousness grade 3, 1 patient
1.7 mg/m2 2 times / week steady, intravenous
MTD
Dose: 1.7 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.7 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Fatigue grade 3, 1 patient
1.7 mg/m2 2 times / week steady, intravenous
MTD
Dose: 1.7 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.7 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Headache grade 3, 1 patient
1.7 mg/m2 2 times / week steady, intravenous
MTD
Dose: 1.7 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.7 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Hypokalemia grade 3, 1 patient
1.7 mg/m2 2 times / week steady, intravenous
MTD
Dose: 1.7 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.7 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Pain grade 3, 1 patient
1.7 mg/m2 2 times / week steady, intravenous
MTD
Dose: 1.7 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.7 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Sensory neuropathy grade 3, 3 patients
1.7 mg/m2 2 times / week steady, intravenous
MTD
Dose: 1.7 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.7 mg/m2, 2 times / week
Sources:
unhealthy, 52 years (range: 26–85 years)
n = 33
Health Status: unhealthy
Condition: recurrent malignant glioma
Age Group: 52 years (range: 26–85 years)
Sex: M+F
Population Size: 33
Sources:
Constipation grade 3, 1%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Pyrexia grade 3, 1%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Rash grade 3, 1%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Anemia grade 3, 12%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Peripheral neuropathy grade 3, 12%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Lymphopenia grade 3, 14%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Thrombocytopenia grade 3, 18%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Leukopenia grade 3, 19%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Anorexia grade 3, 2%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Paresthesia grade 3, 2%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Herpes zoster grade 3, 3%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Nausea grade 3, 3%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Neutropenia grade 3, 30%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Vomiting grade 3, 4%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Asthenia grade 3, 5%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Diarrhea grade 3, 6%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Fatigue grade 3, 6%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Neuralgia grade 3, 8%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Insomnia grade 3, < 1%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Abdominal pain upper grade 3, <1%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Anemia grade 4-5, 1%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Diarrhea grade 4-5, 1%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Fatigue grade 4-5, 1%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Neuralgia grade 4-5, 1%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Peripheral neuropathy grade 4-5, 1%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Neutropenia grade 4-5, 10%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Thrombocytopenia grade 4-5, 17%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Leukopenia grade 4-5, 2%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Lymphopenia grade 4-5, 5%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Co-administed with::
melphalan(9 mg/m2)
prednisone(60 mg/m2)
Sources:
unhealthy, 71 years (range: 48 - 91 years)
n = 340
Health Status: unhealthy
Condition: multiple myeloma
Age Group: 71 years (range: 48 - 91 years)
Sex: M+F
Population Size: 340
Sources:
Hypotension 1%
Disc. AE
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: multiple myeloma |mantle cell lymphoma
Sex: M+F
Population Size: 331
Sources:
Asthenia < 1%
Disc. AE
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: multiple myeloma |mantle cell lymphoma
Sex: M+F
Population Size: 331
Sources:
Pyrexia < 1%
Disc. AE
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: multiple myeloma |mantle cell lymphoma
Sex: M+F
Population Size: 331
Sources:
Weakness < 1%
Disc. AE
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: multiple myeloma |mantle cell lymphoma
Sex: M+F
Population Size: 331
Sources:
Diarrhea 2%
Disc. AE
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Fatigue 2%
Disc. AE
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Thrombocytopenia 2%
Disc. AE
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Peripheral neuropathy 8%
Disc. AE
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Neutropenia grade 3, 11%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Abdominal pain grade 3, 2%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Anorexia grade 3, 2%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Constipation grade 3, 2%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Paresthesia grade 3, 2%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Weakness grade 3, 3%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Anaemia NOS grade 3, 6%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Headache grade 3, <1%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Rash NOS grade 3, <1%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Neutropenia grade 4, 2%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Anaemia NOS grade 4, <1%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Cardiac arrest grade 5, 1 patient
Disc. AE
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Cardiogenic shock grade 5, 1 patient
Disc. AE
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Congestive heart failure grade 5, 1 patient
Disc. AE
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Respiratory insufficiency grade 5, 1 patient
Disc. AE
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Dehydration serious, 2%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Dyspnea serious, 2%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Herpes zoster serious, 2%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Nausea serious, 2%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Pyrexia serious, 2%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Thrombocytopenia serious, 2%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Vomiting serious, 2%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Diarrhea serious, 3%
1.3 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 1.3 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 1.3 mg/m2, 2 times / week
Sources:
unhealthy
n = 331
Health Status: unhealthy
Condition: relapsed multiple myeloma
Sex: M+F
Population Size: 331
Sources:
Overview

OverviewOther

Drug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
The proteasome as a target for cancer therapy.
2003 Dec 15
Blockade of Hsp27 overcomes Bortezomib/proteasome inhibitor PS-341 resistance in lymphoma cells.
2003 Oct 1
Effects of the proteasome inhibitor, bortezomib, on apoptosis in isolated lymphocytes obtained from patients with chronic lymphocytic leukemia.
2003 Oct 1
The bortezomib/proteasome inhibitor PS-341 and triterpenoid CDDO-Im induce synergistic anti-multiple myeloma (MM) activity and overcome bortezomib resistance.
2004 Apr 15
[Treatment with a proteasome inhibitor, bortezomib, for thalidomide-resistant multiple myeloma].
2004 Feb
The proteasome inhibitor bortezomib enhances the activity of docetaxel in orthotopic human pancreatic tumor xenografts.
2004 Jan
Bortezomib and flavopiridol interact synergistically to induce apoptosis in chronic myeloid leukemia cells resistant to imatinib mesylate through both Bcr/Abl-dependent and -independent mechanisms.
2004 Jul 15
Synergistic effect of histone deacetylase inhibitors FK228 and m-carboxycinnamic acid bis-hydroxamide with proteasome inhibitors PSI and PS-341 against gastrointestinal adenocarcinoma cells.
2004 Jun 1
Synergistic induction of oxidative injury and apoptosis in human multiple myeloma cells by the proteasome inhibitor bortezomib and histone deacetylase inhibitors.
2004 Jun 1
Simultaneous inhibition of hsp 90 and the proteasome promotes protein ubiquitination, causes endoplasmic reticulum-derived cytosolic vacuolization, and enhances antitumor activity.
2004 May
Induction of cell cycle arrest and apoptosis by the proteasome inhibitor PS-341 in Hodgkin disease cell lines is independent of inhibitor of nuclear factor-kappaB mutations or activation of the CD30, CD40, and RANK receptors.
2004 May 1
Phase I study of bortezomib in refractory or relapsed acute leukemias.
2004 May 15
Tumour lysis syndrome in multiple myeloma after bortezomib (VELCADE) administration.
2004 Oct
Novel biological therapies for the treatment of multiple myeloma.
2005
Bortezomib, a novel proteasome inhibitor, in the treatment of hematologic malignancies.
2005 Dec
Differential regulation of noxa in normal melanocytes and melanoma cells by proteasome inhibition: therapeutic implications.
2005 Jul 15
PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma.
2005 Jun
Bortezomib abolishes tumor necrosis factor-related apoptosis-inducing ligand resistance via a p21-dependent mechanism in human bladder and prostate cancer cells.
2005 Jun 1
Serum amyloid A-luciferase transgenic mice: response to sepsis, acute arthritis, and contact hypersensitivity and the effects of proteasome inhibition.
2005 Jun 15
NF-kappaB and not the MAPK signaling pathway regulates GADD45beta expression during acute inflammation.
2005 Jun 3
Predominant Bcl-XL knockdown disables antiapoptotic mechanisms: tumor necrosis factor-related apoptosis-inducing ligand-based triple chemotherapy overcomes chemoresistance in pancreatic cancer cells in vitro.
2005 Mar 15
Intracellular protein degradation: from a vague idea, through the lysosome and the ubiquitin-proteasome system, and onto human diseases and drug targeting (Nobel lecture).
2005 Sep 19
Modulation of uridine phosphorylase gene expression by tumor necrosis factor-alpha enhances the antiproliferative activity of the capecitabine intermediate 5'-deoxy-5-fluorouridine in breast cancer cells.
2006 Apr
Bortezomib inhibits docetaxel-induced apoptosis via a p21-dependent mechanism in human prostate cancer cells.
2006 Aug
Anti-cancer effects of bortezomib against chemoresistant neuroblastoma cell lines in vitro and in vivo.
2006 Feb
Vitamin C inactivates the proteasome inhibitor PS-341 in human cancer cells.
2006 Jan 1
The proteasome inhibitor bortezomib induces apoptosis in mantle-cell lymphoma through generation of ROS and Noxa activation independent of p53 status.
2006 Jan 1
Bortezomib-dexamethasone combination in a patient with refractory multiple myeloma and impaired renal function.
2006 Jun
Inhibition of p38alpha MAPK enhances proteasome inhibitor-induced apoptosis of myeloma cells by modulating Hsp27, Bcl-X(L), Mcl-1 and p53 levels in vitro and inhibits tumor growth in vivo.
2006 Jun
Activation of sterile20-like kinase 1 in proteasome inhibitor bortezomib-induced apoptosis in oncogenic K-ras-transformed cells.
2006 Jun 15
Adaphostin and bortezomib induce oxidative injury and apoptosis in imatinib mesylate-resistant hematopoietic cells expressing mutant forms of Bcr/Abl.
2006 Oct
Proteasome inhibitor PS-341 induces apoptosis in cisplatin-resistant squamous cell carcinoma cells by induction of Noxa.
2006 Oct 20
Histone deacetylase inhibitor trichostatin A and proteasome inhibitor PS-341 synergistically induce apoptosis in pancreatic cancer cells.
2006 Oct 6
Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways.
2006 Sep
A novel bioluminescent mouse model and effective therapy for adult T-cell leukemia/lymphoma.
2007 Dec 15
A phase I and pharmacologic study of sequences of the proteasome inhibitor, bortezomib (PS-341, Velcade), in combination with paclitaxel and carboplatin in patients with advanced malignancies.
2007 Feb
SAHA induces apoptosis in hepatoma cells and synergistically interacts with the proteasome inhibitor Bortezomib.
2007 Jul
TRAIL/bortezomib cotreatment is potentially hepatotoxic but induces cancer-specific apoptosis within a therapeutic window.
2007 Mar
Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-kappaB-regulated antiapoptotic and cell survival gene products in human multiple myeloma cells.
2007 Mar 15
Proteasome inhibitors synergize with tumor necrosis factor-related apoptosis-induced ligand to induce anaplastic thyroid carcinoma cell death.
2007 May
The proteasome inhibitor PS-341 (bortezomib) up-regulates DR5 expression leading to induction of apoptosis and enhancement of TRAIL-induced apoptosis despite up-regulation of c-FLIP and survivin expression in human NSCLC cells.
2007 May 15
Capsaicin is a novel blocker of constitutive and interleukin-6-inducible STAT3 activation.
2007 May 15
The proteasome inhibitor bortezomib induces apoptosis in human retinoblastoma cell lines in vitro.
2007 Oct
Bortezomib-associated cutaneous vasculitis.
2007 Oct
Topoisomerase IIbeta mediated DNA double-strand breaks: implications in doxorubicin cardiotoxicity and prevention by dexrazoxane.
2007 Sep 15
PS-341 (Bortezomib) inhibits proliferation and induces apoptosis of megakaryoblastic MO7-e cells.
2008 Jan
Patents

Sample Use Guides

1.3 mg/m2 administered as a 3 to 5 second bolus.
Route of Administration: Intravenous
Fifty % growth inhibition (IC50) in U266, IM-9, and Hs Sultan (multiple myeloma) cells was noted at concentrations of 0.003, 0.006, or 0.02 × 10−6 M, respectively.
Substance Class Chemical
Created
by admin
on Sat Dec 16 09:32:24 GMT 2023
Edited
by admin
on Sat Dec 16 09:32:24 GMT 2023
Record UNII
264LX948L0
Record Status Validated (UNII)
Record Version
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Name Type Language
BORTEZOMIB BORONIC ANHYDRIDE
Common Name English
2-PYRAZINECARBOXAMIDE, N,N',N''-(2,4,6-BOROXINTRIYLTRIS(((1R)-3-METHYLBUTYLIDENE)IMINO((1S)-2-OXO-1-(PHENYLMETHYL)-2,1-ETHANEDIYL)))TRIS-
Systematic Name English
N,N',N''-((2S,2'S,2''S)-(((1R,1'R,1''R)-(1,3,5,2,4,6-TRIOXATRIBORINANE-2,4,6-TRIYL)TRIS(3-METHYLBUTANE-1,1-DIYL))TRIS(AZANEDIYL))TRIS(1-OXO-3-PHENYLPROPANE-1,2-DIYL))TRIS(PYRAZINE-2-CARBOXAMIDE)
Systematic Name English
PYRAZINECARBOXAMIDE, N,N',N''-(2,4,6-BOROXINTRIYLTRIS(((1R)-3-METHYLBUTYLIDENE)IMINO((1S)-2-OXO-1-(PHENYLMETHYL)-2,1-ETHANEDIYL)))TRIS-
Systematic Name English
Code System Code Type Description
PUBCHEM
60071654
Created by admin on Sat Dec 16 09:32:24 GMT 2023 , Edited by admin on Sat Dec 16 09:32:24 GMT 2023
PRIMARY
CAS
390800-88-1
Created by admin on Sat Dec 16 09:32:24 GMT 2023 , Edited by admin on Sat Dec 16 09:32:24 GMT 2023
PRIMARY
FDA UNII
264LX948L0
Created by admin on Sat Dec 16 09:32:24 GMT 2023 , Edited by admin on Sat Dec 16 09:32:24 GMT 2023
PRIMARY
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METABOLITE ACTIVE -> PRODRUG
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