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[Zd 1839 "Iressa"]
J B Meric1, S Faivre, C Monnerat
1Département de médecine, Institut Gustave-Roussy, 39, rue Camille-Desmoulins 94805 Villejuif Cedex.
Abstract:
ZD 1839 is a highly specific EGF receptor tyrosine kinase inhibitor. Inhibition of EGF receptor transphosphorylation by ZD 1839 blocks the signal transduction at the first step, thus providing antiproliferative effects. Preclinical studies demonstrated efficacy and good bioavailability. The terminal half-life of the compound in patients is ranging from 27 to 41 hours, allowing single oral dosing. Tolerance in healthy volunteers was excellent. In phase I studies, toxicity was manageable. Most common side effects were skin rash, nausea, vomiting, and diarrhea. During those studies, clinical responses were observed in patients with various malignant tumors, in particular non small cell lung cancer. Phase II and III studies are ongoing.
Insights
ZD 1839, an epidermal growth factor (EGF) receptor tyrosine kinase inhibitor, shows antiproliferative effects by blocking signal transduction. Clinical trials indicate manageable toxicity and efficacy in various cancers, including non-small cell lung cancer.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Epidermal Growth Factor (EGF) receptor tyrosine kinase signaling pathways are crucial in cancer cell proliferation.
- Targeting these pathways offers a therapeutic strategy for various malignancies.
Purpose of the Study:
- To evaluate the efficacy and safety of ZD 1839, a specific EGF receptor tyrosine kinase inhibitor.
- To assess the pharmacokinetic profile and antiproliferative effects of ZD 1839.
Main Methods:
- Preclinical studies assessing efficacy and bioavailability.
- Phase I clinical trials in healthy volunteers and cancer patients to determine safety, tolerability, and pharmacokinetics.
- Evaluation of clinical responses in patients with various malignant tumors.
Main Results:
- ZD 1839 demonstrated good bioavailability and a terminal half-life of 27-41 hours, allowing single oral dosing.
- Excellent tolerance in healthy volunteers and manageable toxicity in Phase I studies.
- Observed clinical responses in patients with malignant tumors, notably non-small cell lung cancer.
Conclusions:
- ZD 1839 is a well-tolerated and effective inhibitor of the EGF receptor tyrosine kinase.
- The drug exhibits promising antiproliferative effects and warrants further investigation in Phase II and III trials for various cancers.