(1)
Platinum-based
chemotherapy is generally used to treat advanced-stage
non small-cell lung cancer (stages III and IV), but has only a modest impact on survival. There is no reference treatment. (2)
Gefitinib inhibits the
tyrosine kinase activity of the receptor for
EGF (
epidermal growth factor), which is thought to be involved in tumour growth. It has a temporary licence in France and is used on a named-patient basis, but full marketing authorisation has already been granted in Japan, the United States, and elsewhere. (3) Two double-blind dose-finding studies compared two doses of oral
gefitinib monotherapy (250 mg/day and 500 mg/day) in patients in whom at least two lines of
chemotherapy had failed. The results were favourable, with a median survival of 6 months and a symptomatic improvement in some patients, but they are undermined by the absence of a placebo group and by major protocol violations. (4) Two double-blind trials, each in more than 1000 patients, showed that
gefitinib does not increase the efficacy of first-line
platinum combinations. (5) About 15% of patients receiving
gefitinib monotherapy in clinical trials stopped taking the treatment because of adverse events. The most frequent were gastrointestinal (
diarrhea,
nausea,
vomiting) and cutaneous (
rash,
acne, dry skin,
pruritus). (6)
Interstitial pneumonitis occurred in about 1% of patients, and was fatal in about one-third of cases. (7)
Gefitinib is metabolised by the
cytochrome P450 isoenzyme CYP3A4, so carries a potentially high risk of interactions. (8) In practice, more thorough assessment of
gefitinib is needed to determine whether this new
drug is beneficial for patients with
non small-cell lung cancer. Marketing authorisation is not currently justified.