Taxol in ovarian cancer.
Taxol is a structurally complex natural plant product with a novel mechanism of action. The supply of this drug is limited by its low abundance in the bark of the slow-growing yew tree from which it is extracted. The chemical complexity of taxol has hampered the development of a feasible process to synthesize large quantities. Analogues are being made from a precursor found in the needles of the yew tree. However, there is a need to develop a more efficient method to provide adequate supplies of this drug. This review article summarizes the preclinical and clinical studies of taxol in ovarian cancer. Phase I studies have identified the drug's toxicities. Neutropenia has been the dose-limiting toxicity in most trials, and premedications and longer infusion schedules have been used to reduce the incidence and severity of hypersensitivity reactions. The intraperitoneal administration of taxol in Phase I studies showed a pharmacologic advantage with acceptable toxicity. Its activity in ovarian cancer was noticed first in Phase I trials at the Albert Einstein College of Medicine and Johns Hopkins University. These observations led to Phase II testing, which documented response rates of 20-35% in patients with relapsed or refractory ovarian cancer. Phase III trials of taxol and cisplatin versus cyclophosphamide and cisplatin in untreated patients with ovarian cancer are in progress. Studies combining taxol with colony-stimulating factors and cisplatin are ongoing. Taxol is an important new drug in ovarian cancer. Its unique mechanism of action and toxicities make it an attractive agent to use in combination with currently active drugs. Future studies will determine the role of taxol in the management of this disease, but the widespread availability of this drug will depend on the development of a feasible synthetic process.
Runowicz
C D
CD
Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461.
Wiernik
P H
PH
Einzig
A I
AI
Goldberg
G L
GL
Horwitz
S B
SB
D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000627:therapeutic use*; D043823:Taxoids
D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel