Pharmacology of Camptothecin, Irinotecan and Topotecan

[ Chemical Comparison Table | Camptotheca Page ]

[image of camptothecin molecule] Camptothecin is a quinoline-based alkaloid found in the barks of the Chinese camptotheca tree and the Asian nothapodytes tree. It and its close chemical relatives (aminocamptothecin, CPT-11 [irinotecan], DX-8951f, and topotecan) are the only known naturally-occurring DNA topoisomerase I inhibitors. It's one of the newest chemotherapy drugs, and as such cancer researchers are really interested in it, but most incarnations of the drug aren't FDA-approved yet (it and some of its chemical relatives are in clinical trials to treat breast and colon cancers, malignant melanoma, small-cell lung cancer, and leukemia).

On May 29, 1996, the FDA approved topotecan as a treatment for advanced ovarian cancers that have resisted other chemotherapy drugs. Topotecan, which worked as well as or better than Taxol in clinical trials, is manufactured by SmithKline Beecham Pharmeceuticals and is sold under the trade name Hycamtin.

Also, on June 17, 1996, injectable irinotecan HCl was approved as a treatment for metastatic cancer of the colon or rectum; the drug is available under the generic name irinotecan and will be marketed by Pharmacia & Upjohn under the trade name Camptosar. The drug is normally only prescribed in colorectal cancer cases that haven't responded to standard treatment with the chemotherapy agent fluorouracil.

So what does a DNA topoisomerase I inhibitor do, and how does it fight cancer? Topoisomerases are the enzymes that wind and unwind the DNA that makes up the chromosomes. The chromosomes must be unwound in order for the cell to use the genetic information to synthesize proteins; camptothecin keeps the chromosomes wound tight, and so the cell can't make proteins. As a result, the cell stops growing. Because cancer cells grow and reproduce at a much faster rate than normal cells, they are more vulnerable to topoisomerase inhibition than are normal cells.

So far, the major side effects of camptothecin drugs are potentially severe diarrhea, nausea, and lowered leukocyte (white blood cell) counts. The drug may also damage bone marrow.

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This page was last updated 11/6/97.