New natural products in cancer chemotherapy.
Four new and clinically relevant antineoplastic natural products are reviewed. Taxol is derived from the bark of the western yew. It promotes the formation of microtubule bundles which deform the cytoskeleton and interfere with mitosis. Although phase II efficacy testing is incomplete, taxol is effective in the treatment of patients with ovarian carcinoma and has some activity in patients with non-small cell lung cancer and melanoma. It remains untested against several other neoplasms. The chief toxicities of taxol are myelosuppression, mucositis, anaphylactoid reactions, and peripheral neuropathy. Homoharringtonine is the most active and abundant of the cephalotaxine esters derived from the genus Cephalotaxus. This agent appears to act at the ribosome to inhibit protein synthesis and has clinical activity in patients with acute myelogenous leukemia. The dose limiting toxicities of homoharringtonine are hypotension and myelosuppression. SKF 104864 and CPT-11 are derivatives of camptothecin which are still in early clinical trials. They are cytotoxic in vitro, acting through an interaction with topoisomerase I to induce DNA fragmentation. The spectra of activity and toxicity of SKF 104864 and CPT-11 are still undefined. All four of these new natural products offer possibilities for clinical activity for patients with a variety of malignancies.
Slichenmyer
W J
WJ
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7884.
Von Hoff
D D
DD
D000230:Adenocarcinoma / Q000188:drug therapy; D000470:Alkaloids / Q000009:adverse effects / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D055598:Chemical Phenomena; D002621:Chemistry; D015507:Drugs, Investigational; D006248:Harringtonines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077863:Homoharringtonine; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008545:Melanoma / Q000188:drug therapy; D017239:Paclitaxel; D008517:Phytotherapy; D010936:Plant Extracts; D010946:Plants, Medicinal; D019772:Topotecan
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D015507:Drugs, Investigational; D006248:Harringtonines; D010936:Plant Extracts; D000077863:Homoharringtonine; D000077146:Irinotecan; D019772:Topotecan; D017239:Paclitaxel; D002166:Camptothecin