Erlotinib: new drug. Non small-cell lung cancer: like gefitinib, no established advantage.
(1) There is no standard third-line treatment for locally advanced or metastatic non small-cell lung cancer. (2) Erlotinib, like gefitinib, inhibits the tyrosine kinase activity of the epidermal growth factor (EGF) receptor, and has been licensed for sale in the European Union. (3) A double-blind placebo-controlled trial involving 713 patients who had failed to respond to one or two previous chemotherapy regimens showed that erlotinib increased the median survival time by about 2 months (6.7 versus 4.7 months), without improving the quality of this survival. It is not possible to predict precisely which patients are most likely to respond to erlotinib. (4) In first-line treatment, erlotinib was no more effective than placebo as an adjunct to chemotherapy in 2 trials involving 1079 and 1172 patients. (5) The adverse effect profile of erlotinib seems similar to that of gefitinib, mainly consisting of gastrointestinal disturbances (especially diarrhoea: 54% of patients versus 18% on placebo), skin rash (75% versus 17%), and ocular disorders (conjunctivitis: 12% versus 2%). In the comparative trial of second- or third-line treatment, 0.8% of patients developed interstitial pneumonia. (6) Erlotinib, like gefitinib, is metabolized by the cytochrome P450 isoenzyme CYP3A4, potentially creating a high risk of interactions. (7) In practice, the limited benefit of erlotinib seems to be outweighed by its frequent adverse effects. Erlotinib should therefore only be used in clinical trials designed to identify subgroups of patients in whom the risk-benefit balance may be favourable.
D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors