Maintenance Therapy with Gefitinib after First-line Chemotherapy in Patients Affected by Advanced Non-small Cell Lung Cancer

Background: Chemotherapy extends life for patients with advanced non-small cell lung cancer (NSCLC). Second- line treatment of NSCLC includes the use of cytotoxic drugs; however, toxicity is of concern. One molecular target for lung cancer is the epidermal growth factor receptor (EGFR). Gefitinib (Iressai) is an EGFR inhibitor. The aim of our study was to evaluate time to progression (TTP) , overall survival (OS) and toxicities in a population affected by NSCLC using Iressai as maintenance therapy after first-line chemotherapy. Patients and Methods: Thirty patients were enrolled with stable disease or partial response. Six cycles of a platinum-based first- line chemotherapy were administered. Iressai was administered at the dose of 250 mg/d. Results: Median TTP was 5 months; median overall survival was 8 months. TTP for adenocarcinoma and non-adenocarcinoma patients was 10 months and 3.2 months, respectively. No toxic effects were seen in 80% of the patients; 17% of the patients had grade 1 follicolitis. OS for adenocarcinoma and non-adenocarcinoma patients were 15 and 5.9 months, respectively. Conclusion: Gefitinib could be an ideal second-line therapy for adenocarcinoma patients responding to first-line chemotherapy. Lung cancer is the most common cause of cancer death with the vast majority of patients presenting with non-small cell lung cancer (NSCLC) in advanced inoperable stages. The current first-line treatment for patients with local neoplasms is surgery; by contrast, the first-line treatment for advanced NSCLC includes chemotherapy and palliative radiotherapy, but most patients relapse or progress and eventually succumb to the disease, with 5-year survival rates of approximately 15% for all stages (1). At present, chemotherapy extends life and provides symptom palliation for patients with advanced NSCLC. Normally, no more than 4-6 cycles of first-line chemotherapy are performed. Doublets of drugs are usually administered to patients with good performance status; second-line therapy is controversial, especially in asymptomatic patients who have shown a partial response to first-line treatment. It is not clear when second-line treatment shold be started: progression of disease is normally the indicating event, but the response rate is low (about 10-15%), time to progression (TTP) is about 3-4 months and overall survival (OS) does not exceed 8 months after the first-line chemotherapy (2, 3). Current options for the second-line treatment of NSCLC include cytotoxic drugs, such as docetaxel and pemetrexed, and targeted therapies (2-5). Docetaxel was approved in the United States and Europe in 2000 following two Phase III trials that showed the drug's superiority to the best supportive care alone. Pemetrexed was approved in the United States and Europe in 2004 after a Phase III trial, which showed that, compared with docetaxel, it had comparable activity (median survival time of approximately 8 months in both arms) and a more favorable toxicity profile (4, 6). However, chemotherapy toxicity is of concern: a 5.3% rate of grade 3-4 neutropenia was observed in patients with pemetrexed and a 40.2% rate of grade 3-4 neutropenia was seen in patients with docetaxel, while febrile neutropenia was observed in 1.9% versus 12.7% of patients treated with pemetrexed and docetaxel, respectively (3, 4). One molecular target of particular relevance to lung cancer pathogenesis is the epidermal growth factor receptor (EGFR), a cell membrane receptor tyrosine kinase. Several inhibitors of EGFR functional activation have been developed. Among these, erlotinib (Tarceva) and gefitinib (Iressa) are two orally bio-available, small molecule EGFR inhibitors of the tyrosine kinase enzymatic activity which prevent EGFR auto-phosphorylation and activation. In monotherapy, each drug has achieved a 10-20% response rate and a 30-50% symptom improvement in previously treated,