Topotecan hydrochloride (CAS: 119413-54-6)

Basic Information

Topotecan (trade name Hycamtin) is a chemotherapeutic agent that is a topoisomerase inhibitor. It is a water-soluble derivative of camptothecin. It is used in form of the hydrochloride to treat ovarian cancer and lung cancer, as well as other cancer types.

After GlaxoSmithKline received final FDA approval for Hycamtin Capsules on October 15, 2007, topotecan is the firsttopoisomerase I inhibitor for oral use.

Indications (approved uses)

1.Ovarian cancer (FDA May 1996).

2.Cervical cancer (FDA June 2006).

3.Small cell lung cancer (SCLC) (FDA Oct 2007).

Experimental use

1.Neuroblastoma

2.Brainstem glioma

3.Ewing’s sarcoma

Mode of action

Hycamtin or topotecan is a semi-synthetic derivative of camptothecin. Camptothecin is a natural product extracted from the bark of the tree Camptotheca acuminata. Topoisomerase-I is a nuclear enzyme that relieves torsional strain in DNA by opening single strand breaks. Once topoisomerase-I creates a single strand break, the DNA can rotate in front of the advancing replication fork. Topotecan intercalates between DNA bases. This intercalation disrupts the DNA duplication machinery when it reaches a site where topotecan is intercalated. This disruption prevents DNA replication, and ultimately leads to cell death. Mammalian cells cannot efficiently repair these double strand breaks. This process leads to breaks in the DNA strand resulting in apoptosis.

Side effects

1.Myelosuppression

2.Diarrhea

3.Susceptibility to infection