Active Ingredient History
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. NCATS
Drug Pricing (per unit)
Note: This drug pricing data is preliminary, incomplete, and may contain errors.
| Organization | Org Type | FDA approvals | Clinical Trials involvement | Org ID | Force Sort |
|---|
| Organization | Org Type | FDA approvals | Clinical Trials involvement | Org ID | Force Sort |
|---|
Ovarian Neoplasms (approved 1996)
Small Cell Lung Carcinoma (approved 1996)
Adenocarcinoma (Phase 2)
Astrocytoma (Phase 1)
Bone Marrow Cells (Phase 1)
Brain Neoplasms (Phase 2)
Breast Neoplasms (Phase 2)
Brenner Tumor (Phase 1)
Carcinoma (Phase 2)
Carcinoma, Neuroendocrine (Phase 1/Phase 2)
Carcinoma, Non-Small-Cell Lung (Phase 3)
Carcinoma, Ovarian Epithelial (Phase 3)
Carcinoma, Renal Cell (Phase 1)
Carcinoma, Small Cell (Phase 2)
Carcinoma, Squamous Cell (Phase 3)
Central Nervous System Neoplasms (Phase 2)
Choroid Plexus Neoplasms (Phase 1)
Colonic Neoplasms (Phase 2)
Colorectal Neoplasms (Phase 2)
COVID-19 (Phase 3)
Drug Therapy (Phase 2)
Endometrial Neoplasms (Phase 2)
Ependymoma (Phase 2)
Esophageal Neoplasms (Phase 1)
Fallopian Tube Neoplasms (Phase 3)
Ganglioneuroblastoma (Phase 3)
Genital Neoplasms, Female (Phase 1)
Glioblastoma (Phase 2)
Glioma (Phase 2)
Gliosarcoma (Phase 2)
Hamartoma (Phase 3)
Head and Neck Neoplasms (Phase 2)
Hepatoblastoma (Phase 1)
HIV Infections (Phase 2)
Hodgkin Disease (Phase 2)
Intestinal Neoplasms (Phase 1)
Kidney Neoplasms (Phase 2)
Leukemia (Phase 2)
Leukemia, Monocytic, Acute (Phase 2)
Leukemia, Myeloid, Acute (Phase 4)
Leukemia, Myelomonocytic, Acute (Phase 2)
Leukemia, Myelomonocytic, Chronic (Phase 2)
Liposarcoma (Phase 2)
Liver Neoplasms (Phase 2)
Lung Neoplasms (Phase 3)
Lymphoma (Phase 2)
Lymphoma, AIDS-Related (Phase 2)
Lymphoma, Large B-Cell, Diffuse (Phase 2)
Lymphoma, Large-Cell, Anaplastic (Phase 1)
Lymphoma, Large-Cell, Immunoblastic (Phase 2)
Lymphoma, Non-Hodgkin (Phase 2)
Mediastinal Neoplasms (Phase 2)
Medulloblastoma (Phase 2)
Melanoma (Phase 1)
Meningeal Neoplasms (Phase 1)
Meningitis (Phase 1)
Multiple Myeloma (Phase 2)
Myelodysplastic Syndromes (Phase 2)
Myeloproliferative Disorders (Phase 2)
Neoplasm Metastasis (Phase 3)
Neoplasms ()
Neoplasms, Germ Cell and Embryonal (Phase 2)
Neoplasms, Plasma Cell (Phase 1)
Neuroblastoma (Phase 3)
Neuroectodermal Tumors (Phase 3)
Neuroendocrine Tumors (Phase 2)
Neutropenia (Phase 2)
Osteosarcoma (Phase 2)
Ovarian Diseases (Phase 2)
Ovarian Neoplasms (Phase 3)
Pancreatic Neoplasms (Phase 1)
Peritoneal Neoplasms (Phase 1/Phase 2)
Polycythemia Vera (Phase 2)
Precancerous Conditions (Phase 1)
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma (Phase 1/Phase 2)
Primary Myelofibrosis (Phase 2)
Prostatic Neoplasms (Phase 3)
Rectal Neoplasms (Phase 1)
Recurrence (Phase 2)
Retinal Neoplasms (Phase 3)
Retinoblastoma (Phase 3)
Rhabdoid Tumor (Phase 2)
Rhabdomyosarcoma (Phase 3)
Sarcoma (Phase 3)
Sarcoma, Clear Cell (Phase 1)
Sarcoma, Ewing (Phase 3)
Small Cell Lung Carcinoma (Phase 4)
Stomach Neoplasms (Phase 1)
Testicular Neoplasms (Phase 2)
Thrombocythemia, Essential (Phase 2)
Thrombocytopenia (Phase 1/Phase 2)
Urinary Bladder Neoplasms (Phase 2)
Uterine Cervical Neoplasms (Phase 3)
Uterine Neoplasms (Phase 2)
Vaginal Neoplasms (Phase 1)
Vitreoretinopathy, Proliferative (Phase 2)
Vulvar Neoplasms (Phase 1)
Wilms Tumor (Phase 2)
| Trial | Phase | Start Date | Organizations | Indications |
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