RESUMO
Patients with advanced non-small-cell lung cancer (NSCLC) and somatic activating mutations of the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene represent a biologically distinct disease entity that shows exquisite sensitivity to the reversible EGFR-TK inhibitors (-TKIs) gefitinib or erlotinib. Phase III randomized studies have clearly demonstrated that a reversible EGFR-TKI is significantly superior in terms of response rate, progression-free survival and quality of life to platinum-based chemotherapy in advanced NSCLC patients who carry an activating EGFR mutation, thus resulting into a new standard of care for this biologically selected group of patients. Unfortunately, approximately one third of EGFR-mutated patients show primary resistance to gefitinib or erlotinib, whereas virtually all patients who initially benefit from treatment will eventually develop acquired resistance. Importantly, revealing the molecular mechanisms that underlie resistance to reversible EGFR-TKIs is key to the development of EGFR-targeting strategies with the potential to prevent, delay or overcome such resistance. Early results of clinical trials with irreversible EGFR-TKIs or dual combination strategies aiming to block EGFR-mediated signaling at different levels have shown encouraging results in EGFR-mutated patients pretreated or not with a reversible EGFR-TKI. Therefore, in the near future it is reasonable to hypothesize that EGFR-mutated NSCLCs could be treated with multiple lines of EGFR-targeting therapies beyond disease progression, limiting chemotherapy to selected cases of resistant disease. This evolving treatment scenario highlights once again how important is the identification of a single oncogenic "addiction" that functions as unique determinant of progression and survival of NSCLC.
RESUMO
BACKGROUND/AIMS: Lung cancer is the leading cause of cancer death worldwide. There are significant gender differences in lung cancer: most females with lung cancer are non-smokers and they are diagnosed with adenocarcinoma. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are more effective in female lung cancer patients, but the results with gefitinib and erlotinib differ. This study compared the therapeutic response and toxicity of gefitinib and erlotinib in female lung cancer patients. Method: We retrospectively reviewed the clinical information on patients treated with gefitinib or erlotinib for more than one month at Kosin University Gospel Hospital from February 2004 to November 2007. RESULTS: Forty-two patients (26 gefitinib vs. 16 erlotinib) were enrolled during this period. Their median age was 58 years. Thirty-six patients (85%) were non-smokers and 35 patients (83%) had adenocarcinoma. There were 24% at stage IIIb and 76% at stage IV. The median survival time was 793 days. In the gefitinib group, 69% of the patients received 3rd-line chemotherapy, while 12 of 16 (87.5%) in the erlotinib group received 2nd-line chemotherapy. There were no significant differences in the overall response rate (gefitinib 39% vs. erlotinib 31%, p=0.524), median survival time (gefitinib 605 days vs. erlotinib 510 days, p=0.455), and time to progression (gefitinib 186 days vs. erlotinib 262 days, p=0.660). Rashes were more common in the erlotinib group (73.3% vs. 27%, p<0.001). CONCLUSIONS: There were no significant differences in the response rate, overall survival, and time to progression between the two groups. Rashes were more common in the erlotinib group.