U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C39H43N3O11S
Molecular Weight 761.8398
Optical Activity UNSPECIFIED
Defined Stereocenters 7 / 7
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TRABECTEDIN

SMILES

Cc1cc2C[C@@]3([H])[C@@]([H])(N4[C@@]5([H])COC(=O)[C@@]6(CS[C@]([H])(c7c5c8c(c(C)c7OC(=O)C)OCO8)[C@@]4([H])[C@@]([H])(c2c(c1OC)O)N3C)c9cc(c(cc9CCN6)O)OC)O

InChI

InChIKey=PKVRCIRHQMSYJX-AIFWHQITSA-N
InChI=1S/C39H43N3O11S/c1-16-9-20-10-22-37(46)42-23-13-50-38(47)39(21-12-25(48-5)24(44)11-19(21)7-8-40-39)14-54-36(30(42)29(41(22)4)26(20)31(45)32(16)49-6)28-27(23)35-34(51-15-52-35)17(2)33(28)53-18(3)43/h9,11-12,22-23,29-30,36-37,40,44-46H,7-8,10,13-15H2,1-6H3/t22-,23-,29+,30+,36+,37-,39+/m0/s1

HIDE SMILES / InChI
Trabectedin (ET-743) is a marine alkaloid isolated from the Caribbean tunicate Ecteinascidia turbinata. Trabectedin was approved for the treatment of liposarcoma or leiomyosarcoma (USA and Europe) and ovarian cancer (only in Europe). Trabectedin exerts its anti-cancer action by binding guanine residues in the minor groove of DNA. The binding prevents DNA from interacting with transcription factors and the reparation system and results in perturbation of the cell cycle and eventual cell death.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
YONDELIS

Approved Use

YONDELIS is indicated for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen.

Launch Date

1.44555835E12
Primary
YONDELIS

Approved Use

YONDELIS is indicated for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen.

Launch Date

1.44555835E12
Primary
YONDELIS

Approved Use

Yondelis is used to treat adults with two types of cancer: advanced soft-tissue sarcoma, when treatment with anthracyclines and ifosfamide have stopped working, or in patients who cannot be given these medicines; ovarian cancer that has relapsed and is sensitive to medicines containing platinum (in combination with pegylated liposomal doxorubicin).

Launch Date

1.18998722E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
11.3 μg/mL
0.61 mg/m² 1 times / hour multiple, intravenous
dose: 0.61 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
TRABECTEDIN blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
6.47 μg/mL
0.58 mg/m² 3 times / hour multiple, intravenous
dose: 0.58 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
TRABECTEDIN blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
33 ng × h/mL
0.61 mg/m² 1 times / hour multiple, intravenous
dose: 0.61 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
TRABECTEDIN blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
23.5 μg × h/mL
0.58 mg/m² 3 times / hour multiple, intravenous
dose: 0.58 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
TRABECTEDIN blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
3%
TRABECTEDIN plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Disc. AE: ALT increased, AST increased...
AEs leading to
discontinuation/dose reduction:
ALT increased (5.6%)
AST increased (5.6%)
Alkaline phosphatase increased (5.6%)
Bilirubin increased (5.6%)
Thrombocytopenia (3.4%)
Fatigue (1.6%)
Creatine phosphokinase increased (1.1%)
Ejection fraction decreased (1.1%)
Elevated liver enzyme levels (24%)
Neutropenia (8%)
Febrile neutropenia (8%)
Thrombocytopenia (4.2%)
Fatigue (3.7%)
Creatine phosphokinase increased (2.4%)
Nausea (1.1%)
Vomiting (1.1%)
Neutropenia (31%)
Thrombocytopenia (15%)
Elevated liver enzyme levels (6%)
Fatigue (2.9%)
Anemia (2.6%)
Creatinine increased (1.1%)
Sources:
1100 ug/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1100 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1100 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 24–77 years)
n = 6
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 24–77 years)
Sex: M+F
Population Size: 6
Sources:
DLT: Fatigue, Neutropenia...
Other AEs: Nausea, Vomiting...
Dose limiting toxicities:
Fatigue (grade 3, 1 patient)
Neutropenia (grade 4, 1 patient)
Thrombocytopenia (grade 4, 1 patient)
Other AEs:
Nausea (grade 3, 50%)
Vomiting (grade 3, 50%)
ALT increased (grade 3-4, 4 patients)
Alkaline phosphatase increased (grade 1-2, 3 patients)
Hyperbilirubinaemia (grade 3-4, 1 patient)
Anaemia (grade 1-2, 5 patients)
Sources:
1800 ug/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1800 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1800 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 27–71 years)
n = 4
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 27–71 years)
Sex: M+F
Population Size: 4
Sources:
DLT: Fatigue, Thrombocytopenia...
Other AEs: Nausea, Vomiting...
Dose limiting toxicities:
Fatigue (grade 3, 1 patient)
Thrombocytopenia (grade 4, 1 patient)
Bilirubinaemia (grade 3, 1 patient)
Other AEs:
Nausea (50%)
Vomiting (grade 3-4, 50%)
ALT increased (grade 3-4, 3 patients)
Alkaline phosphatase increased (grade 3-4, 1 patient)
Hyperbilirubinaemia (grade 3-4, 1 patient)
Anaemia (grade 1-2, 4 patients)
Sources:
1650 ug/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 1650 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1650 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 27–71 years)
n = 13
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 27–71 years)
Sex: M+F
Population Size: 13
Sources:
DLT: Thrombocytopenia, Neutropenic infection...
Other AEs: Anaemia...
Dose limiting toxicities:
Thrombocytopenia (grade 3, 1 patient)
Neutropenic infection (grade 3, 1 patient)
Other AEs:
Anaemia (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Creatine phosphokinase increased 1.1%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Creatinine increased 1.1%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Ejection fraction decreased 1.1%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Nausea 1.1%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Vomiting 1.1%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Fatigue 1.6%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Thrombocytopenia 15%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Creatine phosphokinase increased 2.4%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Anemia 2.6%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Fatigue 2.9%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Elevated liver enzyme levels 24%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Thrombocytopenia 3.4%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Fatigue 3.7%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Neutropenia 31%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Thrombocytopenia 4.2%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
ALT increased 5.6%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
AST increased 5.6%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Alkaline phosphatase increased 5.6%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Bilirubin increased 5.6%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Elevated liver enzyme levels 6%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Febrile neutropenia 8%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Neutropenia 8%
Disc. AE
1.5 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 17 - 81 years)
n = 345
Health Status: unhealthy
Age Group: 57 years (range: 17 - 81 years)
Sex: M+F
Population Size: 345
Sources:
Alkaline phosphatase increased grade 1-2, 3 patients
1100 ug/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1100 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1100 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 24–77 years)
n = 6
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 24–77 years)
Sex: M+F
Population Size: 6
Sources:
Anaemia grade 1-2, 5 patients
1100 ug/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1100 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1100 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 24–77 years)
n = 6
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 24–77 years)
Sex: M+F
Population Size: 6
Sources:
Fatigue grade 3, 1 patient
DLT
1100 ug/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1100 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1100 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 24–77 years)
n = 6
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 24–77 years)
Sex: M+F
Population Size: 6
Sources:
Nausea grade 3, 50%
1100 ug/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1100 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1100 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 24–77 years)
n = 6
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 24–77 years)
Sex: M+F
Population Size: 6
Sources:
Vomiting grade 3, 50%
1100 ug/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1100 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1100 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 24–77 years)
n = 6
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 24–77 years)
Sex: M+F
Population Size: 6
Sources:
Hyperbilirubinaemia grade 3-4, 1 patient
1100 ug/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1100 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1100 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 24–77 years)
n = 6
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 24–77 years)
Sex: M+F
Population Size: 6
Sources:
ALT increased grade 3-4, 4 patients
1100 ug/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1100 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1100 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 24–77 years)
n = 6
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 24–77 years)
Sex: M+F
Population Size: 6
Sources:
Neutropenia grade 4, 1 patient
DLT
1100 ug/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1100 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1100 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 24–77 years)
n = 6
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 24–77 years)
Sex: M+F
Population Size: 6
Sources:
Thrombocytopenia grade 4, 1 patient
DLT
1100 ug/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1100 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1100 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 24–77 years)
n = 6
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 24–77 years)
Sex: M+F
Population Size: 6
Sources:
Nausea 50%
1800 ug/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1800 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1800 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 27–71 years)
n = 4
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 27–71 years)
Sex: M+F
Population Size: 4
Sources:
Anaemia grade 1-2, 4 patients
1800 ug/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1800 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1800 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 27–71 years)
n = 4
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 27–71 years)
Sex: M+F
Population Size: 4
Sources:
Bilirubinaemia grade 3, 1 patient
DLT
1800 ug/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1800 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1800 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 27–71 years)
n = 4
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 27–71 years)
Sex: M+F
Population Size: 4
Sources:
Fatigue grade 3, 1 patient
DLT
1800 ug/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1800 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1800 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 27–71 years)
n = 4
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 27–71 years)
Sex: M+F
Population Size: 4
Sources:
Alkaline phosphatase increased grade 3-4, 1 patient
1800 ug/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1800 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1800 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 27–71 years)
n = 4
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 27–71 years)
Sex: M+F
Population Size: 4
Sources:
Hyperbilirubinaemia grade 3-4, 1 patient
1800 ug/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1800 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1800 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 27–71 years)
n = 4
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 27–71 years)
Sex: M+F
Population Size: 4
Sources:
ALT increased grade 3-4, 3 patients
1800 ug/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1800 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1800 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 27–71 years)
n = 4
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 27–71 years)
Sex: M+F
Population Size: 4
Sources:
Vomiting grade 3-4, 50%
1800 ug/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1800 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1800 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 27–71 years)
n = 4
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 27–71 years)
Sex: M+F
Population Size: 4
Sources:
Thrombocytopenia grade 4, 1 patient
DLT
1800 ug/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1800 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1800 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 27–71 years)
n = 4
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 27–71 years)
Sex: M+F
Population Size: 4
Sources:
Anaemia 1 patient
1650 ug/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 1650 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1650 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 27–71 years)
n = 13
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 27–71 years)
Sex: M+F
Population Size: 13
Sources:
Neutropenic infection grade 3, 1 patient
DLT
1650 ug/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 1650 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1650 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 27–71 years)
n = 13
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 27–71 years)
Sex: M+F
Population Size: 13
Sources:
Thrombocytopenia grade 3, 1 patient
DLT
1650 ug/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 1650 ug/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1650 ug/m2, 1 times / 3 weeks
Sources:
unhealthy, 57 years (range: 27–71 years)
n = 13
Health Status: unhealthy
Condition: solid tumours
Age Group: 57 years (range: 27–71 years)
Sex: M+F
Population Size: 13
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
inconclusive
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
yes
yes (co-administration study)
Comment: Coadministration of multiple doses of ketoconazole (200 mg twice daily for 7.5 days) with a single dose of YONDELIS (0.58 mg/m2 ) on day 1 increased trabectedin dose-normalized AUC by 66% and Cmax by 22% compared to a single YONDELIS dose (1.3 mg/m2 ) given alone.
Page: 12.0
yes
yes (co-administration study)
Comment: Coadministration of multiple doses of ketoconazole (200 mg twice daily for 7.5 days) with a single dose of YONDELIS (0.58 mg/m2 ) on day 1 increased trabectedin dose-normalized AUC by 66% and Cmax by 22% compared to a single YONDELIS dose (1.3 mg/m2 ) given alone.
Page: 20.0
PubMed

PubMed

TitleDatePubMed
The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux.
2001 May
Pregnane X receptor-dependent and -independent effects of 2-acetylaminofluorene on cytochrome P450 3A23 expression and liver cell proliferation.
2003 Jan 10
Selective effects of the anticancer drug Yondelis (ET-743) on cell-cycle promoters.
2005 Nov
Trabectedin: Ecteinascidin 743, Ecteinascidin-743, ET 743, ET-743, NSC 684766.
2006
Dynamics of cell cycle phase perturbations by trabectedin (ET-743) in nucleotide excision repair (NER)-deficient and NER-proficient cells, unravelled by a novel mathematical simulation approach.
2007 Dec
A Phase II study of trabectedin single agent in patients with recurrent ovarian cancer previously treated with platinum-based regimens.
2007 Dec 17
Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development.
2009
ZNF93 increases resistance to ET-743 (Trabectedin; Yondelis) and PM00104 (Zalypsis) in human cancer cell lines.
2009 Sep 9
Disposition and toxicity of trabectedin (ET-743) in wild-type and mdr1 gene (P-gp) knock-out mice.
2010 Apr
A review of trabectedin (ET-743): a unique mechanism of action.
2010 Aug
Phase I and pharmacokinetic study of sequential paclitaxel and trabectedin every 2 weeks in patients with advanced solid tumors.
2010 May 1
The activity of trabectedin as a single agent or in combination with everolimus for clear cell carcinoma of the ovary.
2011 Jul 1
Patents

Sample Use Guides

Administer at 1.5 mg/m2 body surface area as a 24-hour intravenous infusion, every 3 weeks through a central venous line. Administer dexamethasone 20 mg IV, 30 min before each infusion.
Route of Administration: Intravenous
Human hormone- and drug-resistant prostate cancer cell lines, PC-3 and DU145 were seeded in triplicate in 6-well plates at a density of 1×10(4) cells/well. After 24 h incubation, cells were exposed to increasing concentrations of trabectedin (0.1, 1, 10, 100 nM). Then, plates were incubated at 37C in a 5% CO2 incubator for 24, 48, and 72 h. Trabectedin reduced cell viability in all cell lines. IC50 value of trabectedin was found to be 100 nM for both cell lines after 24 and 48 h, respectively. After 48 h treatment, the IC50 values of trabectedin were found to be 10 nM, 100 nM and 9,2 nM respectively in the DU-145 cell line, DU-145 cancer stem cells (CSCs) and DU-145 non-CSCs. After 72 h treatment, the IC50 values of trabectedin were found to be 1 nM, 9.3 nM and 1 nM respectively in the DU-145 cell line, DU-145 CSCs and DU-145 non-CSCs. After 72 h treatment, the IC50 values of trabectedin were found to be 9 nM, 10 nM and 8 nM respectively in PC-3 cell line, PC-3 CSCs and PC-3 non-CSCs.
Name Type Language
TRABECTEDIN
DASH   EMA EPAR   INN   MART.   USAN   WHO-DD  
USAN   INN  
Official Name English
TRABECTEDIN [USAN]
Common Name English
TRABECTEDIN [MART.]
Common Name English
TRABECTEDIN [WHO-DD]
Common Name English
ECTEINASCIDINS TRABECTEDIN [MI]
Common Name English
TRABECTEDIN [EMA EPAR]
Common Name English
ECTEINASCIDIN 743
Common Name English
TRABECTEDIN [INN]
Common Name English
NSC-648766
Code English
TRABECTEDIN [ORANGE BOOK]
Common Name English
ECTEINASCIDINS TRABECTEDIN
MI  
Common Name English
ET-743
Code English
Classification Tree Code System Code
WHO-ATC L01CX01
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
WHO-VATC QL01CX01
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
EU-Orphan Drug EU/3/03/171
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
FDA ORPHAN DRUG 199004
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
FDA ORPHAN DRUG 193604
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
EMA ASSESSMENT REPORTS YONDELIS (AUTHORIZED: OVARIAN NEOPLASMS)
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
NDF-RT N0000175558
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
NCI_THESAURUS C2115
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
Code System Code Type Description
INN
8206
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
PRIMARY
ChEMBL
CHEMBL1224207
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
PRIMARY
FDA UNII
ID0YZQ2TCP
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
PRIMARY
MESH
C099150
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
PRIMARY
DRUG BANK
DB05109
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
PRIMARY
DRUG CENTRAL
4633
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
PRIMARY
NCI_THESAURUS
C1691
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
PRIMARY
JAPANESE REVIEW
YONDELIS
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
PRIMARY APPROVE SEPTEMBER 2015
IUPHAR
2774
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
PRIMARY
CAS
114899-77-3
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
PRIMARY
EPA CompTox
114899-77-3
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
PRIMARY
RXCUI
1716278
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
PRIMARY RxNorm
PUBCHEM
108150
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
PRIMARY
MERCK INDEX
M4820
Created by admin on Sat Jun 26 05:46:18 UTC 2021 , Edited by admin on Sat Jun 26 05:46:18 UTC 2021
PRIMARY Merck Index