RESUMO
BACKGROUND: Several Asian studies demonstrated feasibility of front-line administration of gefitinib for the treatment of non-small cell lung carcinomas (NSCLCs) harboring intragenic epidermal growth factor receptor (EGFR) mutations. The experience of the use of this EGFR tyrosine kinase inhibitor (TKI) in non-Asian subjects remains limited. PATIENTS AND METHODS: The study included lung adenocarcinoma (AC) patients treated at the N.N. Petrov Institute of Oncology (Russia). RESULTS: DNA analysis of 192 consecutive AC revealed 38 (20%) TKI-sensitizing mutations. Presence of the exon 19 deletion (del19) or L858R was strongly correlated with nonsmoking status (smokers: 8/98 (8%); non-smokers: 30/94 (32%); p = 0.00004). The efficacy of first-line gefitinib therapy was evaluated in 25 patients with EGFR-mutated advanced AC. Twelve (48%) cases demonstrated tumor response (1 (4%) complete response, 11 (44%) partial responses; 10/17 (59%) patients with del19 mutation vs. 2/8 (25%) cases with L858R substitution, p = 0.11). The remaining 13 (52%) patients experienced disease stabilization. Median progression-free survival was 8.0 months. Grade 3 toxicity was the maximal adverse event, being observed only in 4 (16%) cases. CONCLUSION: Gefitinib may be considered as an upfront treatment option for EGFR-mutated NSCLC.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Antineoplásicos/uso terapêutico , Análise Mutacional de DNA , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Deleção Cromossômica , Intervalo Livre de Doença , Éxons/genética , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Tirosina Quinases/antagonistas & inibidores , Quinazolinas/efeitos adversos , Federação Russa , Resultado do TratamentoAssuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Cisplatino/uso terapêutico , Genes BRCA1 , Adulto , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Non-small cell lung carcinomas (NSCLC) carrying a mutation in the epidermal growth factor receptor (EGFR) gene show unprecedented sensitivity to gefitinib or erlotinib. CASE REPORTS: We present the follow-up data of 2 EGFR mutation-positive stage IV NSCLC patients who received upfront 250 mg gefitinib daily, then underwent potentially curative surgery, and resumed gefitinib therapy in the adjuvant setting. Patient 1 was diagnosed with a rightsided adenocarcinoma of the upper lobe with multiple metastases to the middle lobe. After 2 months of gefitinib treatment, only a small primary lesion was seen, and a bilobectomy with lymph node dissection was performed. The patient remained disease-free during a scheduled 12-month adjuvant therapy but relapsed 9 weeks after cessation of this treatment. Patient 2 presented with adenocarcinoma of the lower lobe of the right lung and a single metastasis to the left adrenal. After 3 months of receiving gefitinib, the metastasis was no longer detectable, and the primary tumor was significantly reduced. Surgery included lobectomy and adrenalectomy. This patient relapsed with metastasis in the remaining adrenal 4 months after the start of adjuvant therapy. CONCLUSION: Gefitinib can be used preoperatively for the management of advanced EGFR mutation-positive NSCLC. It remains to be established whether surgical intervention indeed renders survival advantage for this category of patients.