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
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
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 |
DescriptionSources: http://www.drugbank.ca/drugs/DB01030Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020671s021lbl.pdf
Sources: http://www.drugbank.ca/drugs/DB01030
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14755016
Curator's Comment: freely crosses the blood-brain barrier
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1781 Sources: http://www.drugbank.ca/drugs/DB01030 |
1028.0 nM [IC50] | ||
Target ID: CHEMBL392 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21463912 |
3.16 µM [IC50] | ||
Target ID: CHEMBL614697 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21463912 |
0.448 µM [IC50] | ||
Target ID: CHEMBL394 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21463912 |
1.1 µM [IC50] | ||
Target ID: DNA |
|||
Target ID: CHEMBL384 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8182764 |
33.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | HYCAMTIN Approved UseHYCAMTIN 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 Date8.3315517E11 |
|||
Primary | HYCAMTIN Approved UseHYCAMTIN 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 Date8.3315517E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
9.29 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26291057 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
61 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26291057 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5.23 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26291057 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
65% |
TOPOTECAN plasma | Homo sapiens |
Doses
Dose | Population | Adverse 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) Sources: 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) |
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) Sources: 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) |
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%) Sources: 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%) |
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... |
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%) Sources: Anemia (grade 3-4, 11%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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
Title | Date | PubMed |
---|---|---|
Comparison of in vitro activities of camptothecin and nitidine derivatives against fungal and cancer cells. | 1999 Dec |
|
Phase II trial of topotecan in patients with advanced, persistent, or recurrent uterine leiomyosarcomas: a Gynecologic Oncology Group Study. | 2000 Aug |
|
The inhibitory effects of camptothecin, a topoisomerase I inhibitor, on collagen synthesis in fibroblasts from patients with systemic sclerosis. | 2001 |
|
A phase I-II trial of topotecan and gemcitabine in patients with previously treated, advanced non-small cell lung cancer (LOA-3). | 2001 |
|
Topotecan and gemcitabine in platinum/paclitaxel-resistant ovarian cancer. | 2001 |
|
Phase I dose escalation study of topotecan combined with alternating schedules of paclitaxel and carboplatin in advanced solid tumors. | 2001 Apr |
|
New agents for induction and postremission therapy of acute myeloid leukemia. | 2001 Apr |
|
Unusual potency of BN 80915, a novel fluorinated E-ring modified camptothecin, toward human colon carcinoma cells. | 2001 Apr 1 |
|
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 |
|
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 |
|
Clonal heterogeneity of p53 mutations in ovarian cancer. | 2001 Aug |
|
Resistance to topoisomerase poisons due to loss of DNA mismatch repair. | 2001 Aug 15 |
|
Modulation of camptothecin analogs in the treatment of cancer: a review. | 2001 Feb |
|
Clear cell carcinoma of the ovary: a remarkable case. | 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 |
|
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 |
|
The HER tyrosine kinase inhibitor CI1033 enhances cytotoxicity of 7-ethyl-10-hydroxycamptothecin and topotecan by inhibiting breast cancer resistance protein-mediated drug efflux. | 2001 Jan 15 |
|
Glioma cell sensitivity to topotecan: the role of p53 and topotecan-induced DNA damage. | 2001 Jan 19 |
|
Paclitaxel plus topotecan treatment for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma. | 2001 Jul |
|
Effective dosing of topotecan with carboplatin in relapsed ovarian cancer: a phase I/II study. | 2001 Jul 1 |
|
Topotecan selectively enhances the radioresponse of human small-cell lung carcinoma and glioblastoma multiforme xenografts in nude mice. | 2001 Jul 1 |
|
Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. | 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 |
|
Oligodendroglial ganglioglioma with anaplastic features arising from the thalamus. | 2001 Jun |
|
Topotecan chemotherapy in patients with breast cancer and brain metastases: results of a pilot study. | 2001 Jun |
|
[Evaluation of quality of life in patients with advanced colorectal cancer treated with topotecan]. | 2001 Mar |
|
Characterization of a novel topoisomerase I mutation from a camptothecin-resistant human prostate cancer cell line. | 2001 Mar 1 |
|
Phase II trial of topotecan, carboplatin, and paclitaxel as front-line therapy in suboptimal advanced epithelial ovarian cancer. | 2001 May |
|
Repetitive high-dose topotecan, carboplatin, and paclitaxel with peripheral blood progenitor cell support in previously untreated ovarian cancer: results of a Phase I study. | 2001 May |
|
[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 |
|
[Interaction of topotecan--a DNA topoisomerase inhibitor--with dual-stranded polydeoxyribonucleotides. I. Dimerization of topotecan in solution]. | 2001 May-Jun |
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8603419
In DC3F hamster lung fibroblasts, 2.5 uM topotecan caused redistribution of topo I to nonnucleolar regions of the nucleus.
Substance Class |
Chemical
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C185435
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1228035-86-6
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