Hycamptin - General Information
An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA topoisomerases, type I. [PubChem]
Pharmacology of Hycamptin
Hycamptin, 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. Hycamptin interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells may also 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.
Hycamptin for patients
Pharmacokinetic studies of the interaction of topotecan with concomitantly administered medications have not been formally investigated. In vitro inhibition studies using marker substrates known to be metabolized by human P450 CYP1A2, CYP2A6, CYP2C8/9, CYP2C19, CYP2D6, CYP2E, C.P.A. or CYP4A or dihydropyrimidine dehydrogenase indicate that the activities of these enzymes were not altered by topotecan. Enzyme inhibition by topotecan has not been evaluated in vivo.
Concomitant administration of G-CSF can prolong the duration of neutropenia, so if G-CSF is to be used, it should not be initiated until day 6 of the course of therapy, 24 hours after completion of treatment with Hycamtin .
Myelosuppression was more severe when Hycamtin was given in combination with cisplatin in Phase I studies. In a reported study on concomitant administration of cisplatin 50 mg/m2 and Hycamtin at a dose of 1.25 mg/m2/day x 5 days, one of three patients had severe neutropenia for 12 days and a second patient died with neutropenic sepsis. There are no adequate data to define a safe and effective regimen for Hycamtin and cisplatin in combination.
Hycamtin is contraindicated in patients who have a history of hypersensitivity reactions to topotecan or to any of its ingredients. Hycamtin should not be used in patients who are pregnant or breast-feeding, or those with severe bone marrow depression.
Additional information about Hycamptin
Hycamptin Indication: For the treatment of metastatic carcinoma of the ovary and small cell lung cancer following the failure of first-line chemotherapy.
Mechanism Of Action: Hycamptin has the same mechanism of action as irinotecan. Topoisomerase I relieves torsional strain in DNA by inducing reversible single strand breaks. Hycamptin binds to the topoisomerase I-DNA complex and prevents religation of these single strand breaks. The cytotoxicity of topotecan is thought to be due to double strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topotecan, topoisomerase I and DNA. Mammalian cells cannot efficiently repair these double strand breaks.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Topotecan
Synonyms: TPT; TTC; Topotecanum [Inn-Latin]; Topotecane [Inn-French]; Topotecan Lactone; Topotecan Hydrochloride; Topotecan Hcl
Drug Category: Antineoplastic Agents; Enzyme Inhibitors
Drug Type: Small Molecule; Approved
Absorption: Not Available
Toxicity (Overdose): The primary anticipated complication of overdosage would consist of bone marrow suppression.
Protein Binding: 35%
Biotransformation: Topotecan undergoes a reversible pH dependent hydrolysis of its lactone moiety; it is the lactone form that is pharmacologically active.
Half Life: 2-3 hours
Dosage Forms of Hycamptin: Powder, for solution Intravenous
Chemical IUPAC Name: (S)-10-[(dimethylamino) methyl]-4-ethyl-4,9-dihydroxy-1H-pyrano[3', 4']
Chemical Formula: C23H23N3O5
Topotecan on Wikipedia: https://en.wikipedia.org/wiki/Topotecan
Organisms Affected: Humans and other mammals