The role of targeted therapy in non-small cell lung cancer.

The therapy of non-small cell lung cancer (NSCLC) has reached a plateau in improving patient survival, with overall disappointing results. Thus, clinical research for new treatment strategies is warranted. Advances in the singling out molecular targets for NSCLC treatment has granted the development of several new biological agents. In the present paper we describe the main clinical data currently available on targeted agents in the treatment of NSCLC, focusing on epidermal growth factor receptor family inhibitors, angiogenesis inhibitors, signal transduction inhibitors, eicosanoid pathway inhibitors, vaccines and gene therapy. Several targeted agents have been introduced into clinical trials in NSCLC, mainly in advanced disease, with the first phase III study results being recently made available. To date, few of these new agents can offer hope of a substantial impact on the natural history of NSCLC, and negative results are more commonly reported than positive ones. Nevertheless, clinically-meaningful advances have already been achieved in chemotherapy refractory advanced NSCLC patients, with gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, representing a further chance of tumor control and symptom palliation. Moreover, important lessons can be learned from this first generation of clinical trials.

Gefitinib as salvage therapy in pretreated patients with advanced non-small cell lung cancer. Data from a compassionate use program.

PURPOSE: To evaluate the tolerabiliy and activity of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with pretreated advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: From July 2001 to August 2003, we analysed, retrospectively, the data of 125 previously treated advanced NSCLC patients receiving gefitinib 250 mg, orally once daily in a compassionate use program. RESULTS: Main toxicity was (% of patients): grade 1-2 skin changes in 7 (5.0%) and 8 (6.4%) patients, respectively. Grade 1 diarrhea in 16 (12.8%) patients. Grade 1 and 2 hypertransaminasemia in 1 (0.8%) patient, respectively. Grade 2 onychopathy in 1 (0.8%) patient and epistaxis in 1 (0.8%) case. There were 1 complete response (0.8%), 6 partial responses (4.8%) and 22 (17.6%) stable disease with an overall control of disease in 23.2% of cases. Median progression-free survival and overall survival were 8.8 and 21.5 weeks, respectively. CONCLUSION: Gefitinib is active, feasible and well-tolerated in pretreated patients affected by advanced NSCLC.

Treatment of pulmonary neuroendocrine tumours: state of the art and future developments.

The current classification of pulmonary neuroendocrine tumours includes four subtypes: low-grade typical carcinoid tumour (TC), intermediate-grade atypical carcinoid tumour (AC), and two high-grade malignancies: large cell neuroendocrine carcinoma and small cell lung cancer (SCLC). Unfortunately, with the exclusion of SCLC, no large phase II and III trials for pulmonary neuroendocrine tumours have been published. Thus, several treatment approaches are available for their treatment but none of them has been validated in appropriately designed and adequately sized clinical trials. The main problem of the published studies is that they include neuroendocrine tumours from various sites of origin with different clinical behaviour. It is important that future studies consider these tumours separately. In this regard, increased awareness and referral of these patients to tertiary centres, in which a multidisciplinary management is available, may be of value. The aim of this review is to evaluate the state of the art and discuss future developments in the management of pulmonary neuroendocrine tumours excluding SCLC which we consider should be addressed in a different issue.