The camptothecins.
Supported by detailed understanding of their mechanism of action, and facilitated by chemical manipulations that have amplified their solubility, the camptothecins have advanced to the forefront of several areas of therapeutic and developmental chemotherapy. Additive and synergistic laboratory interactions with other cytotoxic drugs have been exploited to allow development of camptothecin-based multidrug regimens, which are showing important activity in several malignancies. Topotecan and irinotecan are already in widespread use in clinical practice, and newer agents with promising preclinical activity are in various stages of clinical assessment. As knowledge of molecular and biochemical mechanisms of action and resistance continues to expand, newer and better camptothecin-based strategies for treatment of malignant disease are likely to evolve.
Pizzolato
Joseph F
JF
Memorial Sloan-Kettering Cancer Center, Gastrointestinal Oncology Service, 1275 York Avenue, New York, NY 10021, USA. saltzl@mskcc.org <saltzl@mskcc.org>
Saltz
Leonard B
LB
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D018288:Carcinoma, Small Cell / Q000188:drug therapy; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D059004:Topoisomerase I Inhibitors; D002166:Camptothecin