Related Experiment Videos
Gefitinib
Christine R Culy1, Diana Faulds
1Adis International Limited, Mairangi Bay, Auckland, New Zealand. demail@adis.co.nz
Abstract:
Gefitinib (ZD1839) is an orally active selective inhibitor of epidermal growth factor receptor tyrosine kinase, an enzyme that regulates intracellular signalling pathways implicated in the proliferation and survival of cancer cells. In human non-small cell lung cancer (NSCLC) cell lines and xenografts, gefitinib dose-dependently inhibited cellular proliferation and tumour growth, and potentiated the cytotoxic effects of chemotherapy and/or radiation. Gefitinib is orally bioavailable and is cleared via the cytochrome P450 3A4 pathway. In patients receiving gefitinib (50 to 700 mg/day) in phase I trials, steady-state plasma concentration was reached in 7 to 10 days. In patients with advanced NSCLC who had failed one or two prior chemotherapies, gefitinib 250 or 500mg once daily induced an objective response in approximately 19% of patients in a double-blind trial (n = 210). In another double-blind trial including 216 patients with NSCLC who had failed two or more prior chemotherapies, gefitinib 250 or 500mg once daily induced an objective response in 11.8 and 8.8% of patients, respectively; approximately 40% showed an improvement in disease-related symptoms. Gefitinib was generally well tolerated and the most common adverse events were mild skin rashes and diarrhoea.
Insights
Gefitinib, an epidermal growth factor receptor inhibitor, demonstrated efficacy in non-small cell lung cancer (NSCLC) patients. It showed objective responses and symptom improvement, with manageable side effects like rash and diarrhea.
Area of Science:
- Oncology
- Pharmacology
Background:
- Epidermal growth factor receptor (EGFR) signaling pathways are crucial for cancer cell proliferation and survival.
- Targeting EGFR tyrosine kinase offers a potential therapeutic strategy for cancer treatment.
Purpose of the Study:
- To evaluate the efficacy and tolerability of gefitinib, an orally active selective EGFR tyrosine kinase inhibitor, in patients with advanced non-small cell lung cancer (NSCLC).
Main Methods:
- Gefitinib's effects on NSCLC cell lines and xenografts were assessed for cellular proliferation and tumor growth inhibition.
- Clinical trials evaluated gefitinib's oral bioavailability, pharmacokinetic profile (CYP450 3A4 pathway), and efficacy in NSCLC patients who had failed prior chemotherapy.
- Objective response rates and disease-related symptom improvements were measured in double-blind trials.
Main Results:
- Gefitinib demonstrated dose-dependent inhibition of proliferation and tumor growth in preclinical models.
- In advanced NSCLC patients, gefitinib (250-500 mg/day) achieved objective response rates of approximately 19% and 11.8-8.8% in different trials.
- Around 40% of patients experienced improvement in disease-related symptoms, and the drug was generally well tolerated with common side effects including mild rash and diarrhea.
Conclusions:
- Gefitinib is an orally bioavailable EGFR tyrosine kinase inhibitor with demonstrated activity in advanced NSCLC.
- The drug shows potential as a treatment option for NSCLC patients, particularly those who have progressed on prior chemotherapy.
- Gefitinib exhibits a generally favorable safety profile, with manageable adverse events.