250 mg tablets
Approved indication: non-small cell lung cancer
Australian Medicines Handbook section 14.3
Growth factors have an important role in regulating cell proliferation. Abnormalities in the receptors for growth factors can result in cancer development. The epidermal growth factor receptor may be involved in transmitting cellular signals that lead to the progression of lung cancer. These signals can be blocked by inhibiting the enzyme tyrosine kinase.
Gefitinib is a tyrosine kinase inhibitor which can be taken by mouth. It has a bioavailability of 59%, but absorption is not altered by fasting. Gefitinib is metabolised by cytochrome P450 3A4 so it has the potential to interact with drugs that induce, or are metabolised by, this enzyme system. Interactions with itraconazole and rifampicin have been confirmed in volunteers. In clinical trials there have been interactions with metoprolol and possibly warfarin. As most of the drug is eliminated by liver metabolism and, as liver enzymes can increase during treatment, patients should have their liver function checked.
In an early clinical trial gefitinib was given to 71 patients with a variety of cancers that had not responded to other treatment. Although several patients dropped out of the trial, 26 completed at least three months of therapy. Only nine of the 39 patients with non-small cell lung cancer continued treatment for three months. The major dose-limiting toxicities were diarrhoea and rash.1
When used as monotherapy for previously-treated patients with locally advanced or metastatic non-small cell lung cancer gefitinib has produced a response in 9-19% of patients. Although treatment relieved some patients' symptoms, the median survival was only 6-8 months. When used in combination with other anticancer drugs in previously untreated patients gefitinib does not improve survival.
Most patients will suffer adverse effects from treatment. These include diarrhoea, rashes and other skin problems, nausea and vomiting. Australian Prescriber's sister journal in Japan, Kusuri-no-Check, has been concerned about deaths from gefitinib. Approximately 23 500 people have been treated in Japan, but the drug has been implicated in the deaths of 183.2Many of these deaths may have been the result of acute interstitial pneumonia.3
Although gefitinib has been marketed before the results of clinical trials have been published, its role in therapy will require further study. Its Australian approval restricts it to patients with locally advanced or metastatic non-small cell lung cancer who have previously received chemotherapy.
- Herbst RS, Maddox AM, Rothenberg ML, Small EJ, Rubin EH, Baselga J, et al. Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: results of a phase I trial. J Clin Oncol 2002;20:3815-25.
- Hama R, Sakaguchi K. The gefitinib story. ISDB Newsletter 2003;17:6-9.
- Inoue A, Saijo Y, Maemondo M, Gomi K, Tokue Y, Kimura Y, et al. Severe acute interstitial pneumonia and gefitinib. Lancet 2003;361:137-9.