Erlotinib after failure of gefitinib in patients with advanced non-small cell lung cancer previously responding to gefitinib.
BACKGROUND
Gefitinib and erlotinib are two orally active epidermal growth factor receptor tyrosine kinase inhibitors used in the treatment of advanced non-small cell lung cancer (NSCLC). Gefitinib was the first one to become available in Europe in an expanded access program. When erlotinib granted approval, there were many patients who had progressed after receiving gefitinib and different lines of chemotherapy with no further treatment options; moreover, the results of clinical trials suggested possible significant differences in the mechanisms of sensitivity and in the efficacy between these two agents.


METHODS
Advanced NSCLC White patients, previously treated with almost two lines of chemotherapy and with gefitinib, obtaining a partial response or a stable disease with this agent, were treated with erlotinib after progression of disease to gefitinib. Only eight patients resulted eligible because of the unavailability of gefitinib after the closure of the expanded access program.


RESULTS
Four patients were women; histologic diagnosis was adenocarcinoma in four cases and bronchoalveolar carcinoma or unspecified NSCLC in two cases each. Median age was 70 years (range, 53-85). Seven out of eight patients had never smoked, one was a former smoker.We obtained two partial responses and three stable diseases with erlotinib with a median duration of response of 8 months. The median time to progression and overall survival were 5.9 and 14.6 months, respectively.


CONCLUSIONS
Erlotinib seems to be a potential therapeutic option for treatment of selected advanced NSCLC patients after failure of gefitinib. Further studies are warranted to evaluate the molecular mechanisms behind this evidence and clarify how to select patients for treatment with epidermal growth factor receptor tyrosine kinase inhibitors.
Vasile
Enrico
E
Department of Oncology Azienda USL-6 of Livorno, Istituto Toscano Tumori, Livorno, Italy. envasile@tin.it
Tibaldi
Carmelo
C
Chella
Antonio
A
Falcone
Alfredo
A
D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib