Camptothecin and its analogs. An overview of their potential in cancer therapeutics.
From the outset of their clinical testing the camptothecins have shown antitumor activity against gastrointestinal cancer. With the definition of mechanism of action and introduction of several analogs their antitumor activity spectrum has expanded to include ovarian, cervical, small-cell and non-small cell lung cancers and malignant lymphomas, among others. The wide range of trials in these disease areas have been reviewed for CPT-11, topotecan, and 9-aminocamptothecin. A therapeutic role is anticipated for these and other camptothecins in these disease sites. Issues in guiding treatment indications and clinical development include: 1) pharmacokinetics and scheduling relevant to each of the drugs, with the oral route emerging as a practical way for testing prolonged exposure; 2) dose-intensification with cytokines, and its relevance in maintaining effective doses particularly in combination with other myelosuppressive drugs; and 3) pharmacodynamic determinants of response-an area of research that is particularly attractive because topoisomerase I is the target for camptothecins.
Muggia
F M
FM
Department of Medicine, University of Southern California-Kenneth Norris Jr. Comprehensive Cancer Center, Los Angeles 90033, USA.
Dimery
I
I
Arbuck
S G
SG
D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D018288:Carcinoma, Small Cell / Q000188:drug therapy; D002986:Clinical Trials as Topic; D005260:Female; D019337:Hematologic Neoplasms / Q000188:drug therapy; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy; D014594:Uterine Neoplasms / Q000188:drug therapy
D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin