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Details

Stereochemistry ABSOLUTE
Molecular Formula 4C23H23N3O5.5ClH
Molecular Weight 1868.088
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TOPOTECAN HYDROCHLORIDE (1:1.25)

SMILES

Cl.Cl.Cl.Cl.Cl.CC[C@@]1(O)C(=O)OCC2=C1C=C3N(CC4=C3N=C5C=CC(O)=C(CN(C)C)C5=C4)C2=O.CC[C@@]6(O)C(=O)OCC7=C6C=C8N(CC9=C8N=C%10C=CC(O)=C(CN(C)C)C%10=C9)C7=O.CC[C@@]%11(O)C(=O)OCC%12=C%11C=C%13N(CC%14=C%13N=C%15C=CC(O)=C(CN(C)C)C%15=C%14)C%12=O.CC[C@@]%16(O)C(=O)OCC%17=C%16C=C%18N(CC%19=C%18N=C%20C=CC(O)=C(CN(C)C)C%20=C%19)C%17=O

InChI

InChIKey=ZTUHNABKVPMUSC-LDERQKGUSA-N
InChI=1S/4C23H23N3O5.5ClH/c4*1-4-23(30)16-8-18-20-12(9-26(18)21(28)15(16)11-31-22(23)29)7-13-14(10-25(2)3)19(27)6-5-17(13)24-20;;;;;/h4*5-8,27,30H,4,9-11H2,1-3H3;5*1H/t4*23-;;;;;/m0000...../s1

HIDE SMILES / InChI

Molecular Formula C23H23N3O5
Molecular Weight 421.4458
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020671s021lbl.pdf

Topotecan, a semi-synthetic derivative of camptothecin (a plant alkaloid obtained from the Camptotheca acuminata tree), is an anti-tumor drug with topoisomerase I-inhibitory activity similar to irinotecan. DNA topoisomerases are enzymes in the cell nucleus that regulate DNA topology (3-dimensional conformation) and facilitate nuclear processes such as DNA replication, recombination, and repair. During these processes, DNA topoisomerase I creates reversible single-stranded breaks in double-stranded DNA, allowing intact single DNA strands to pass through the break and relieve the topologic constraints inherent in supercoiled DNA. The 3'-DNA terminus of the broken DNA strand binds covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the unaltered topoisomers that allow transcription to proceed. Topotecan interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells can be affected by the medicine, other effects may also occur. Unlike irinotecan, topotecan is found predominantly in the inactive carboxylate form at neutral pH and it is not a prodrug. Topotecan has the same mechanism of action as irinotecan and is believed to exert its cytotoxic effects during the S-phase of DNA synthesis. Topoisomerase I relieves torsional strain in DNA by inducing reversible single strand breaks. Topotecan binds to the topoisomerase I-DNA complex and prevents religation of these single strand breaks. This ternary complex interferes with the moving replication fork, which leads to the induction of replication arrest and lethal double-stranded breaks in DNA. As mammalian cells cannot efficiently repair these double strand breaks, the formation of this ternary complex eventually leads to apoptosis (programmed cell death). Topotecan mimics a DNA base pair and binds at the site of DNA cleavage by intercalating between the upstream (−1) and downstream (+1) base pairs. Intercalation displaces the downstream DNA, thus preventing religation of the cleaved strand. By specifically binding to the enzyme–substrate complex, Topotecan acts as an uncompetitive inhibitor. Topotecan is used for the treatment of advanced ovarian cancer in patients with disease that has recurred or progressed following therapy with platinum-based regimens. Also used as a second-line therapy for treatment-sensitive small cell lung cancer, as well as in combination with cisplatin for the treatment of stage IV-B, recurrent, or persistent cervical cancer not amenable to curative treatment with surgery and/or radiation therapy. Topotecan is sold under the trade name Hycamtin.

CNS Activity

Curator's Comment: freely crosses the blood-brain barrier

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
1028.0 nM [IC50]
3.16 µM [IC50]
0.448 µM [IC50]
1.1 µM [IC50]
33.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
HYCAMTIN

Approved Use

HYCAMTIN for injection is a topoisomerase inhibitor indicated for: • metastatic carcinoma of the ovary after disease progression on or after initial or subsequent chemotherapy. • small cell lung cancer platinum-sensitive disease in patients who progressed after first-line chemotherapy. • combination therapy with cisplatin for Stage IV-B, recurrent, or persistent carcinoma of the cervix which is not amenable to curative treatment.

Launch Date

8.3315517E11
Primary
HYCAMTIN

Approved Use

HYCAMTIN for injection is a topoisomerase inhibitor indicated for: • metastatic carcinoma of the ovary after disease progression on or after initial or subsequent chemotherapy. • small cell lung cancer platinum-sensitive disease in patients who progressed after first-line chemotherapy. • combination therapy with cisplatin for Stage IV-B, recurrent, or persistent carcinoma of the cervix which is not amenable to curative treatment.

Launch Date

8.3315517E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
9.29 ng/mL
4 mg single, oral
dose: 4 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TOPOTECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
61 ng × h/mL
4 mg single, oral
dose: 4 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TOPOTECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
5.23 h
4 mg single, oral
dose: 4 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TOPOTECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
65%
TOPOTECAN plasma
Homo sapiens
Doses

Doses

DosePopulationAdverse events​
10.5 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 10.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 10.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Other AEs: Leukopenia, Leukopenia...
Other AEs:
Leukopenia (grade 1, 1 patient)
Leukopenia (grade 2, 1 patient)
Leukopenia (grade 3, 7 patients)
Leukopenia (grade 4, 2 patients)
Neutropenia (grade 2, 6 patients)
Neutropenia (grade 3, 2 patients)
Neutropenia (grade 4, 1 patient)
Thrombocytopenia (grade 1, 2 patients)
Thrombocytopenia (grade 2, 1 patient)
Thrombocytopenia (grade 3, 1 patient)
Thrombocytopenia (grade 4, 2 patients)
Anemia (grade 1, 3 patients)
Anemia (grade 2, 3 patients)
Anemia (1 patient)
Sources:
8.4 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 8.4 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 8.4 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Other AEs: Leukopenia, Leukopenia...
Other AEs:
Leukopenia (grade 1, 4 patients)
Leukopenia (grade 2, 4 patients)
Leukopenia (grade 3, 3 patients)
Leukopenia (grade 4, 1 patient)
Neutropenia (grade 1, 1 patient)
Neutropenia (grade 2, 2 patients)
Neutropenia (grade 3, 1 patient)
Neutropenia (grade 4, 1 patient)
Thrombocytopenia (grade 2, 3 patients)
Thrombocytopenia (grade 3, 2 patients)
Anemia (grade 1, 4 patients)
Anemia (grade 2, 1 patient)
Anemia (grade 3, 1 patient)
Anemia (3 patients)
Sources:
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Other AEs: Leukopenia, Leukopenia...
Other AEs:
Leukopenia (grade 3, 40.7%)
Leukopenia (grade 4, 15.9%)
Neutropenia (grade 3, 31%)
Neutropenia (grade 4, 50.4%)
Thrombocytopenia (grade 3, 17.7%)
Thrombocytopenia (grade 4, 22.1%)
Anemia (grade 3, 26.5%)
Anemia (grade 4, 2.7%)
Nausea (grade 1, 31.9%)
Nausea (grade 2, 25%)
Nausea (grade 3, 5.2%)
Alopecia (grade 1, 19.8%)
Alopecia (grade 2, 22.4%)
Alopecia (grade 3, 4.3%)
Fatigue (grade 1, 22.4%)
Fatigue (grade 2, 10.3%)
Fatigue (grade 3, 5.2%)
Vomiting (grade 1, 12.1%)
Vomiting (grade 2, 19.8%)
Vomiting (grade 3, 4.3%)
Vomiting (grade 4, 0.9%)
Diarrhea (grade 1, 19%)
Diarrhea (grade 2, 13.8%)
Diarrhea (grade 3, 1.7%)
Diarrhea (grade 4, 0.9%)
Sources:
1.5 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / day
Sources:
unhealthy, adult
n = 859
Health Status: unhealthy
Condition: ovarian cancer | small cell lung cancer
Age Group: adult
Sex: M+F
Population Size: 859
Sources:
Other AEs: Neutropenia...
Other AEs:
Neutropenia (grade 4, 58%)
Sources:
1.5 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / day
Sources:
unhealthy, adult
n = 862
Health Status: unhealthy
Condition: ovarian cancer | small cell lung cancer
Age Group: adult
Sex: M+F
Population Size: 862
Sources:
Other AEs: Thrombocytopenia, Anemia...
Other AEs:
Thrombocytopenia (grade 4, 20%)
Anemia (grade 3-4, 11%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Anemia 1 patient
10.5 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 10.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 10.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Leukopenia grade 1, 1 patient
10.5 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 10.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 10.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Thrombocytopenia grade 1, 2 patients
10.5 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 10.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 10.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Anemia grade 1, 3 patients
10.5 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 10.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 10.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Leukopenia grade 2, 1 patient
10.5 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 10.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 10.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Thrombocytopenia grade 2, 1 patient
10.5 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 10.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 10.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Anemia grade 2, 3 patients
10.5 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 10.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 10.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Neutropenia grade 2, 6 patients
10.5 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 10.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 10.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Thrombocytopenia grade 3, 1 patient
10.5 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 10.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 10.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Neutropenia grade 3, 2 patients
10.5 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 10.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 10.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Leukopenia grade 3, 7 patients
10.5 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 10.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 10.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Neutropenia grade 4, 1 patient
10.5 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 10.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 10.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Leukopenia grade 4, 2 patients
10.5 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 10.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 10.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Thrombocytopenia grade 4, 2 patients
10.5 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 10.5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 10.5 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Anemia 3 patients
8.4 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 8.4 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 8.4 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Neutropenia grade 1, 1 patient
8.4 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 8.4 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 8.4 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Anemia grade 1, 4 patients
8.4 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 8.4 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 8.4 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Leukopenia grade 1, 4 patients
8.4 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 8.4 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 8.4 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Anemia grade 2, 1 patient
8.4 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 8.4 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 8.4 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Neutropenia grade 2, 2 patients
8.4 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 8.4 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 8.4 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Thrombocytopenia grade 2, 3 patients
8.4 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 8.4 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 8.4 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Leukopenia grade 2, 4 patients
8.4 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 8.4 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 8.4 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Anemia grade 3, 1 patient
8.4 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 8.4 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 8.4 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Neutropenia grade 3, 1 patient
8.4 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 8.4 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 8.4 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Thrombocytopenia grade 3, 2 patients
8.4 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 8.4 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 8.4 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Leukopenia grade 3, 3 patients
8.4 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 8.4 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 8.4 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Leukopenia grade 4, 1 patient
8.4 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 8.4 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 8.4 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Neutropenia grade 4, 1 patient
8.4 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 8.4 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 8.4 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 54 years (range: 34-75 years)
n = 25
Health Status: unhealthy
Condition: solid tumors
Age Group: 54 years (range: 34-75 years)
Sex: M+F
Population Size: 25
Sources:
Vomiting grade 1, 12.1%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Diarrhea grade 1, 19%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Alopecia grade 1, 19.8%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Fatigue grade 1, 22.4%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Nausea grade 1, 31.9%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Fatigue grade 2, 10.3%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Diarrhea grade 2, 13.8%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Vomiting grade 2, 19.8%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Alopecia grade 2, 22.4%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Nausea grade 2, 25%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Diarrhea grade 3, 1.7%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Thrombocytopenia grade 3, 17.7%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Anemia grade 3, 26.5%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Neutropenia grade 3, 31%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Alopecia grade 3, 4.3%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Vomiting grade 3, 4.3%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Leukopenia grade 3, 40.7%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Fatigue grade 3, 5.2%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Nausea grade 3, 5.2%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Diarrhea grade 4, 0.9%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Vomiting grade 4, 0.9%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Leukopenia grade 4, 15.9%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Anemia grade 4, 2.7%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Thrombocytopenia grade 4, 22.1%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Neutropenia grade 4, 50.4%
2.3 mg/m2 1 times / day multiple, oral
Recommended
Dose: 2.3 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 2.3 mg/m2, 1 times / day
Sources:
unhealthy, 62.1 years (range: 38-86 years)
n = 116
Health Status: unhealthy
Condition: ovarian cancer
Age Group: 62.1 years (range: 38-86 years)
Sex: F
Population Size: 116
Sources:
Neutropenia grade 4, 58%
1.5 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / day
Sources:
unhealthy, adult
n = 859
Health Status: unhealthy
Condition: ovarian cancer | small cell lung cancer
Age Group: adult
Sex: M+F
Population Size: 859
Sources:
Anemia grade 3-4, 11%
1.5 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / day
Sources:
unhealthy, adult
n = 862
Health Status: unhealthy
Condition: ovarian cancer | small cell lung cancer
Age Group: adult
Sex: M+F
Population Size: 862
Sources:
Thrombocytopenia grade 4, 20%
1.5 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 1.5 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 1.5 mg/m2, 1 times / day
Sources:
unhealthy, adult
n = 862
Health Status: unhealthy
Condition: ovarian cancer | small cell lung cancer
Age Group: adult
Sex: M+F
Population Size: 862
Sources:
PubMed

PubMed

TitleDatePubMed
A phase I-II trial of topotecan and gemcitabine in patients with previously treated, advanced non-small cell lung cancer (LOA-3).
2001
Phase II and pharmacokinetic/pharmacodynamic trial of sequential topoisomerase I and II inhibition with topotecan and etoposide in advanced non-small-cell lung cancer.
2001
Topotecan and gemcitabine in platinum/paclitaxel-resistant ovarian cancer.
2001
ICE bioassay. Isolating in vivo complexes of enzyme to DNA.
2001
New agents for induction and postremission therapy of acute myeloid leukemia.
2001 Apr
Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918.
2001 Apr
Determination of topotecan by ELISA.
2001 Apr
Clinical evidence for topotecan-paclitaxel non--cross-resistance in ovarian cancer.
2001 Apr 1
A prospective randomized phase II trial of GM-CSF priming to prevent topotecan-induced neutropenia in chemotherapy-naive patients with malignant melanoma or renal cell carcinoma.
2001 Apr 1
Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues.
2001 Apr 15
Topotecan versus observation after cisplatin plus etoposide in extensive-stage small-cell lung cancer: E7593--a phase III trial of the Eastern Cooperative Oncology Group.
2001 Apr 15
Topotecan given as a 21-day infusion in the treatment of advanced ovarian cancer.
2001 Apr 20
A mutation in subunit B of the DNA polymerase alpha-primase complex from Novikoff hepatoma cells concomitant with a conformational change and abnormal catalytic properties of the DNA polymerase alpha-primase complex.
2001 Aug
Pharmacodynamic model of topotecan-induced time course of neutropenia.
2001 Aug
Altretamine is an effective palliative therapy of patients with recurrent epithelial ovarian cancer.
2001 Feb
Modulation of camptothecin analogs in the treatment of cancer: a review.
2001 Feb
Lack of efficacy of topotecan in the treatment of metastatic or recurrent squamous carcinoma of the head and neck: an Eastern Cooperative Oncology Group Trial (E3393).
2001 Feb
Selective drug resistant human osteosarcoma cell lines.
2001 Feb
Topotecan concomitant with primary brachytherapy radiation in patients with cervical carcinoma: a phase I trial.
2001 Feb
Evaluation of topotecan and etoposide for non-Hodgkin lymphoma: correlation of topoisomerase-DNA complex formation with clinical response.
2001 Feb 1
P53 modulates the effect of loss of DNA mismatch repair on the sensitivity of human colon cancer cells to the cytotoxic and mutagenic effects of cisplatin.
2001 Feb 15
Phase I study of topotecan plus cranial radiation for glioblastoma multiforme: results of Radiation Therapy Oncology Group Trial 9507.
2001 Feb 15
Breast cancer resistance protein directly confers SN-38 resistance of lung cancer cells.
2001 Feb 9
Current treatment for ovarian cancer.
2001 Jan
The role of systemic chemotherapy in the treatment of brain metastases from small-cell lung cancer.
2001 Jan
Fludarabine, cytarabine and topotecan (FLAT) as induction therapy for acute myeloid leukemia in the elderly: a preliminary report.
2001 Jan
Response and toxicity to topotecan in sensitive ovarian cancer cases with small residual disease after first-line treatment with carboplatinum and paclitaxel.
2001 Jan
Prevention of human smooth muscle cell proliferation without induction of apoptosis by the topoisomerase I inhibitor topotecan.
2001 Jan 1
Up-front window trial of topotecan in previously untreated children and adolescents with metastatic rhabdomyosarcoma: an intergroup rhabdomyosarcoma study.
2001 Jan 1
Glioma cell sensitivity to topotecan: the role of p53 and topotecan-induced DNA damage.
2001 Jan 19
Advances in the management of epithelial ovarian cancer.
2001 Jul
Interaction between novel anticancer agents and radiation in non-small cell lung cancer cell lines.
2001 Jul
UCN-01 dose-dependent inhibition of normal hyperproliferative cells in mice.
2001 Jul
Topotecan selectively enhances the radioresponse of human small-cell lung carcinoma and glioblastoma multiforme xenografts in nude mice.
2001 Jul 1
CCNU-dependent potentiation of TRAIL/Apo2L-induced apoptosis in human glioma cells is p53-independent but may involve enhanced cytochrome c release.
2001 Jul 12
Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan.
2001 Jul 15
Antisense oligonucleotides targeting the epidermal growth factor receptor inhibit proliferation, induce apoptosis, and cooperate with cytotoxic drugs in human cancer cell lines.
2001 Jul 15
Sensitivity to topoisomerase I inhibitors and cisplatin is associated with epidermal growth factor receptor expression in human cervical squamous carcinoma ME180 sublines.
2001 Jun
[Evaluation of quality of life in patients with advanced colorectal cancer treated with topotecan].
2001 Mar
The epidermal growth factor receptor as a target for cancer therapy.
2001 Mar
Topoisomerase I inhibition with topotecan: pharmacologic and clinical issues.
2001 Mar
Topoisomerase I targeting agents in small-cell lung cancer.
2001 Mar
Characterization of a novel topoisomerase I mutation from a camptothecin-resistant human prostate cancer cell line.
2001 Mar 1
A Phase II study of topotecan in patients with squamous cell carcinoma of the cervix: a gynecologic oncology group study.
2001 May
Topoisomerase IIalpha and other drug resistance markers in advanced non-small cell lung cancer.
2001 May
Loss of expression of a new member of the DNAJ protein family confers resistance to chemotherapeutic agents used in the treatment of ovarian cancer.
2001 May 15
Feasibility of four consecutive high-dose chemotherapy cycles with stem-cell rescue for patients with newly diagnosed medulloblastoma or supratentorial primitive neuroectodermal tumor after craniospinal radiotherapy: results of a collaborative study.
2001 May 15
[Interaction of topotecan--a DNA topoisomerase I inhibitor--with dual-stranded polydeoxyribonucleotides. II. Formation of a complex containing several DNA molecules in the presence of topotecan].
2001 May-Jun
Advances in chemotherapy for small cell lung cancer: single-agent activity of newer agents.
2001 May-Jun
High-dose topotecan, melphalan, and cyclophosphamide (TMC) with stem cell support: a new regimen for the treatment of advanced ovarian cancer.
2001 Sep
Patents

Sample Use Guides

Ovarian cancer and small cell lung cancer: 1.5 mg/m2 by intravenous infusion over 30 minutes daily for 5 consecutive days, starting on Day 1 of a 21-day course. Cervical cancer: 0.75 mg/m2 by intravenous infusion over 30 minutes on Days 1, 2, and 3 repeated every 21 days in combination with cisplatin 50 mg/m2 on Day 1
Route of Administration: Intravenous
In Vitro Use Guide
In DC3F hamster lung fibroblasts, 2.5 uM topotecan caused redistribution of topo I to nonnucleolar regions of the nucleus.
Substance Class Chemical
Created
by admin
on Thu Jul 06 20:16:50 UTC 2023
Edited
by admin
on Thu Jul 06 20:16:50 UTC 2023
Record UNII
O0BO5T84GD
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TOPOTECAN HYDROCHLORIDE (1:1.25)
USAN  
Official Name English
FF 10850 [WHO-DD]
Common Name English
NOGITECAN HYDROCHLORIDE (4:5)
JAN  
Common Name English
1H-Pyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione, 10-[(dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-, hydrochloride (4:5), (4S)-
Systematic Name English
HYCAMPTAMINE HYDROCHLORIDE (4:5)
Common Name English
(S)-10-((DIMETHYLAMINO)METHYL)-4-ETHYL-4,9-DIHYDROXY-1H-PYRANO(3',4':6,7)INDOLIZINO(1,2-B)QUINOLINE-3,14(4H,12H)-DIONE HYDROCHLORIDE (4:5)
Systematic Name English
Code System Code Type Description
NCI_THESAURUS
C185435
Created by admin on Thu Jul 06 20:16:50 UTC 2023 , Edited by admin on Thu Jul 06 20:16:50 UTC 2023
PRIMARY
CAS
1228035-86-6
Created by admin on Thu Jul 06 20:16:50 UTC 2023 , Edited by admin on Thu Jul 06 20:16:50 UTC 2023
PRIMARY
FDA UNII
O0BO5T84GD
Created by admin on Thu Jul 06 20:16:50 UTC 2023 , Edited by admin on Thu Jul 06 20:16:50 UTC 2023
PRIMARY
NCI_THESAURUS
C80065
Created by admin on Thu Jul 06 20:16:50 UTC 2023 , Edited by admin on Thu Jul 06 20:16:50 UTC 2023
ALTERNATIVE
PUBCHEM
139593475
Created by admin on Thu Jul 06 20:16:50 UTC 2023 , Edited by admin on Thu Jul 06 20:16:50 UTC 2023
PRIMARY
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