RESUMEN
OBJECTIVES: Sorafenib and erlotinib are potent, orally administered receptor tyrosine kinase inhibitors with antiproliferative and antiangiogenic activities. Given their synergistic activity in combination, we conducted a phase II study to determine the clinical activity of sorafenib in combination with erlotinib in patients with advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with advanced NSCLC who have received one or two prior chemotherapy regimens for metastatic disease, ECOG 0-2, and adequate organ function were eligible. Patients received 400mg twice daily sorafenib and 150 mg daily erlotinib in 28-day cycles. Epidermal growth factor receptor mutation and its downstream pathways were analyzed from available tumor samples. Changes in plasma cytokine and angiogenic factors were correlated with clinical outcomes. RESULTS: A total of 46 patients were enrolled. Twenty patients (43%) were never smokers and 35 patients (75%) had adenocarcinoma histology. The overall response rate was 30.4%. Response to sorafenib/erlotinib was observed more commonly in patients with EGFR mutation than in those with EGFR wild type (WT) or EGFR unknown tumors (62.5% vs. 6.7% vs. 34.8%; P=0.013). Likewise, DCR was higher among patients with EGFR mutation than in those with EGFR WT or EGFR unknown tumors (87.5% vs. 46.7% vs. 60.9%; P=0.161). The most frequent adverse events (AEs) of all grades were hand-foot skin reaction (67.4%) followed by acneiform rash (58.7%). CONCLUSION: Sorafenib combined with erlotinib is well-tolerated with manageable toxicity and appears to be effective against advanced NSCLC with one or two prior line of systemic treatment (NCT00801385).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Progresión de la Enfermedad , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Clorhidrato de Erlotinib/administración & dosificación , Femenino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Mutación , Estadificación de Neoplasias , Niacinamida/administración & dosificación , Niacinamida/análogos & derivados , Compuestos de Fenilurea/administración & dosificación , Proteínas Proto-Oncogénicas p21(ras)/genética , Factores de Riesgo , Sorafenib , Resultado del TratamientoRESUMEN
OBJECTIVE: This prospective multicenter study conducted by the Korean Cancer Study Group evaluated the efficacy and safety of pemetrexed in Korean patients with advanced non-small cell lung cancer (NSCLC) who had prior chemotherapy. PATIENTS AND METHODS: Patients with stage IIIB or IV NSCLC in whom prior chemotherapy failed received pemetrexed 500 mg/m(2) every 3 weeks with folic acid and vitamin B12 supplementation until disease progression or the development of intolerable toxicity. Eighty-one patients were enrolled. RESULTS: The overall response rate for 78 evaluable patients was 5.1% [95% confidence interval (CI) 1.4-12.6; partial response 4/78, no complete response]. The disease control rate including complete, partial response and stable disease was 46.2% (36/78, 95% CI 34.8-57.8). With a median 8.7 months follow-up, the median time to progression was 3.1 months (95% CI 1.17-5.03) and the median overall survival (OS) was 7.8 months (95% CI 5.19-10.35). The median OS for patients with adenocarcinoma histology was 18.7 months compared to 6.1 months for non-adenocarcinoma. In a multivariate analysis, Eastern Cooperative Oncology Group performance status 0-1 [hazards ratio (HR)=0.331, 95% CI 0.135-0.814] and adenocarcinoma (HR=0.504, 95% CI 0.283-0.899) were independent factors for prolongation of overall survival. CONCLUSIONS: Pemetrexed monotherapy has promising efficacy in patients with advanced NSCLC as a second-line therapy with less hematologic and non-hematologic toxicity, especially in those with adenocarcinoma histology.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Glutamatos/administración & dosificación , Guanina/análogos & derivados , Neoplasias Pulmonares/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Femenino , Glutamatos/efectos adversos , Guanina/administración & dosificación , Guanina/efectos adversos , Humanos , Corea (Geográfico) , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pemetrexed , Estudios Prospectivos , Análisis de SupervivenciaRESUMEN
PURPOSE: This prospective trial was conducted to evaluate the role of gefitinib in never-smokers with advanced or metastatic adenocarcinoma of the lung. PATIENTS AND METHODS: The main inclusion criteria were stage IIIB/IV adenocarcinoma of the lung and status as a lifetime never-smoker. Patients received a 250-mg single oral daily dose of gefitinib until disease progression, unacceptable toxicity, or patient's refusal. Tumor response was assessed after every two 4-week cycles according to the World Health Organization response criteria. Additional analyses were performed to identify predictors of response and survival. RESULTS: Between August 2003 and March 2005, 72 Korean patients were enrolled; 55 chemotherapy naive, 17 previously treated; 6 male, 66 female; and ECOG PS 0/1/2, 24/42/4. All patients were assessed for response, toxicity, quality of life, and survival. Overall objective tumor response rate was 55.6% (95% confidence interval [CI], 43.4-67.3%). With a median follow-up of 23 months, the median survival time was 19.7 months (95% CI, 18.5-21.0 months) with a 1-year survival rate of 76.3%. The median duration of response was 6.8 months (95% CI, 4.7-9.0 months). Therapy-related improvement of symptoms and quality of life was observed within 2 to 4 weeks after the commencement of therapy in the responders. In a multivariate Cox proportional hazard model, good performance status and no prior history of chemotherapy were the two significant predictors of better survival (p = 0.005 and 0.042). CONCLUSION: Gefitinib showed very promising antitumor activity and survival outcome in Korean never-smokers with adenocarcinoma of the lung. It seems to be a good alternative to standard chemotherapy as a first-line therapy for this subgroup.