[Camptothecin and derivatives: a new class of antitumor agents]

Abstract

Camptothecin (CPT), an alkaloid isolated from the stem wood and bark of Camptotheca acuminata native to China, was discovered in the early 60's after a systematic screening of natural products by the National Cancer Institute (NCI). This new anticancer agent displays an unique mechanism of action as it inhibits intranuclear enzyme topoisomerase 1, involved in DNA replication. CPT is poorly water soluble and causes severe and unpredictable toxicities such as haemorrhagic cystitis and diarrhea; for therefore reason, a number of analogues have been synthetized in a attempt to define the features of the molecule that are essential for cytotoxicity and to produce derivatives with increased solubility. Clinical trials of several soluble molecules are in progress in the different countries: irinotecan, topotecan, 9-AC. Encouraging results are observed against solid tumors. Irinotecan was recently commercialized in France. It is a prodrug; the active metabolite SN-38 showed a good activity in metastatic colorectal adenocarcinoma; the limiting toxicities are myelotoxicity and essentially late diarrhea. However, new studies are needed for state precisely the optimal schedule of administration and association with other chemotherapeutic agents.