Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C39H43N3O11S |
Molecular Weight | 761.837 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 7 / 7 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]12[C@@H]3SC[C@]4(NCCC5=CC(O)=C(OC)C=C45)C(=O)OC[C@H](N1[C@@H](O)[C@@H]6CC7=CC(C)=C(OC)C(O)=C7[C@H]2N6C)C8=C3C(OC(C)=O)=C(C)C9=C8OCO9
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
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
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: DNA |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | YONDELIS Approved UseYONDELIS is indicated for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen. Launch Date2015 |
|||
Primary | YONDELIS Approved UseYONDELIS is indicated for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen. Launch Date2015 |
|||
Primary | YONDELIS Approved UseYondelis 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 Date2007 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
11.3 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19417019 |
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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19417019 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
33 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19417019 |
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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19417019 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3% |
TRABECTEDIN plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse 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%) Sources: 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%) |
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) Other AEs:Neutropenia (grade 4, 1 patient) Thrombocytopenia (grade 4, 1 patient) Nausea (grade 3, 50%) Sources: 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) |
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) Other AEs:Thrombocytopenia (grade 4, 1 patient) Bilirubinaemia (grade 3, 1 patient) Nausea (50%) Sources: 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) |
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) Other AEs:Neutropenic infection (grade 3, 1 patient) Anaemia (1 patient) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207953Orig1s000ClinPharmR.pdf#page=24 Page: 24.0 |
yes | |||
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: 12.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207953Orig1s000ClinPharmR.pdf#page=20 Page: 20.0 |
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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207953Orig1s000ClinPharmR.pdf#page=20 Page: 20.0 |
PubMed
Title | Date | PubMed |
---|---|---|
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 |
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Trabectedin : a review of its use in the management of soft tissue sarcoma and ovarian cancer. | 2007 |
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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 |
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A Phase II study of trabectedin single agent in patients with recurrent ovarian cancer previously treated with platinum-based regimens. | 2007 Dec 17 |
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Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. | 2009 |
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Disposition and toxicity of trabectedin (ET-743) in wild-type and mdr1 gene (P-gp) knock-out mice. | 2010 Apr |
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A review of trabectedin (ET-743): a unique mechanism of action. | 2010 Aug |
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Phase I and pharmacokinetic study of sequential paclitaxel and trabectedin every 2 weeks in patients with advanced solid tumors. | 2010 May 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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26485709
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.
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YONDELIS (AUTHORIZED: OVARIAN NEOPLASMS)
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YONDELIS
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ACTIVE MOIETY
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