|
|
Topoisomerase
I Inhibitors
Ewesuedo
RB, Ratain MJ
Section
of Pediatric Hematology-Oncology, Department of Pediatrics and Committee on
Clinical Pharmacology, Cancer Research Center, University of Chicago, Chicago,
Illinois, 60637, USA. mjratain@mcis.bsd.uchicago.edu
Topoisomerase
I inhibitors are a new class of anticancer agents with a mechanism of action
aimed at interrupting DNA replication in cancer cells, the result of which is
cell death.
Most if not all Topoisomerase I inhibitors are derivatives of the plant extract
camptothecin.
Irinotecan (CPT-11), a semi-synthetic derivative of camptothecin, is approved in
the United States for the treatment of colorectal cancer.
Ongoing clinical trials with CPT-11 show a 13% to 32% response rate when it is
used singly or in combination with other chemotherapeutic agents such as
5-fluorouracil.
The major dose-limiting toxicities of CPT-11 are myelosuppression and a dual
phase diarrhea.
Topotecan is another semi-synthetic analogue of camptothecin. It is approved for
use in the United States for the treatment of cisplatin refractory ovarian
carcinoma.
Current clinical trials suggest antitumor activity against a variety of human
tumor types.
There is significant interindividual variability in the plasma disposition of
this drug.
The main dose-limiting toxicity is myelosuppression.
There are other derivatives of camptothecin, as well as new formulations of the
parent plant extract, that are in various stages of clinical trials.
Some of these clinical trials are aimed at increasing the therapeutic benefits
of the agents when used singly or in combination with other chemotherapeutic
agent(s) or treatment modalities.
The dose-limiting toxicity observed in most of these clinical trials is
myelosuppression.
PMID:
10388070 [PubMed - as supplied by publisher]
|