The role of cetuximab and other epidermal growth factor receptor monoclonal antibodies in the treatment of advanced non-small cell lung cancer.

Lung cancer continues to be the leading cause of cancer-related deaths in the western civilization and developing countries. Non-small cell lung cancer (NSCLC) accounts for > 85% of all cases of lung cancer. Since most patients with NSCLC have advanced disease at diagnosis, to date chemotherapy with third-generation platinum-based doublets represents the standard of care.

Combined chemo-radiotherapy for locally advanced non-small cell lung cancer: current status and future development.

Currently, combinations of chemotherapy and radiotherapy are the standard treatment approach for locally advanced NSCLC patients. Concomitant chemo-radiotherapy, although associated with increased acute toxicity, has demonstrated to be the better strategy over sequential chemoradiotherapy, and it is to be considered a standard approach in patients with good performance status (0-1). However, the approach to locally advanced NSCLC and to chemo-radiotherapy regimens remains heterogeneous among oncologists, and clinical outcomes are yet disappointing.

New insights in drug development for the non-small cell lung cancer therapy.

Non-small cell lung cancer (NSCLC) remains a major problem worldwide. Since most patients with NSCLC have advanced disease at diagnosis, to date, chemotherapy, with third-generation platinum-based doublets, represents the standard of care. However, a plateau has been reached with the use of cytotoxic chemotherapy in advanced NSCLC.

Acute and fatal diarrhoea after erlotinib plus abdominal palliative hypofractionated radiotherapy in a metastatic non-small cell lung cancer patient: a case report.

The management of advanced non-small cell lung cancer (NSCLC) has progressed over the last 3 decades due to advances in chemotherapeutic drugs and targeted agents improving survival and quality of life. In particular erlotinib, an orally available human epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor advancing through clinical trials for the treatment of various human malignancies in a large placebo-controlled phase III study, has shown a significantly better OS vs. placebo suggesting its potential benefits in third line and possibly in second line treatments.

The potential role of histone deacetylase inhibitors in the treatment of non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) arises from a complex series of genetic and epigenetic changes leading to uncontrolled cell growth and metastases. The exponential growth in the level of research about the histone deacetylase (HDAC) enzymes, responsible for deacetylating core nucleosomal histones and other proteins, has been driven by the ability of HDAC inhibitors to modulate transcriptional activity. As a result, this therapeutic class is able to block angiogenesis and cell cycling, and promote apoptosis and differentiation.

Second-line treatment of advanced non-small cell lung cancer.

After failure of first-line chemotherapy for advanced non-small cell lung cancer, many patients remain candidates to receive further antitumor treatment. To guide clinical management of these patients and to suggest priorities for clinical research, an International Panel of Experts met in Naples (Italy) in April 2007. Results and evidence-based conclusions are presented in this article.

The potential role of mTOR inhibitors in non-small cell lung cancer.

The mammalian target of rapamycin (mTOR), a serine/threonine kinase, is a downstream mediator in the phosphatidylinositol 3-kinase/Akt signaling pathway, which plays a critical role in regulating basic cellular functions including cellular growth and proliferation. Currently, the mTOR inhibitor rapamycin and its analogues (CCI-779, RAD001, AP23573), which induce cell-cycle arrest in the G(1) phase, are being evaluated in cancer clinical trials. The mTOR inhibitors appear to be well tolerated, with skin reactions, stomatitis, myelosuppression, and metabolic abnormalities the most common toxicities seen.

A randomized phase II study of pemetrexed or RAD001 as second-line treatment of advanced non-small-cell lung cancer in elderly patients: treatment rationale and protocol dynamics.

In the current clinical trial summary, we present a randomized phase II trial of pemetrexed or RAD001 as second-line treatment of elderly patients with advanced non-small-cell lung cancer. The molecular and clinical rationale is reviewed. The primary endpoint is progression-free survival, and secondary endpoints include objective tumor response rates, disease control rates, safety, tolerability, and overall survival.

The role of bevacizumab in the treatment of non-small cell lung cancer: current indications and future developments.

The majority of non-small cell lung cancer (NSCLC) patients present with advanced disease, and despite the improvement in efficacy and safety outcomes with platinum-based chemotherapy, this standard cytotoxic approach has reached a therapeutic plateau, with the prognosis for this clinical condition remaining poor. Advances in the knowledge of tumor biology and mechanisms of oncogenesis have granted the singling out of several molecular targets for NSCLC treatment. Bevacizumab, an anti-growth factor vascular endothelial growth factor (VEGF) monoclonal antibody, is the antiangiogenic agent at the most advanced stage of development in the treatment of solid tumors and also in NSCLC treatment.

Erlotinib in non-small-cell lung cancer.

Epidermal growth factor receptor (EGFR) plays an essential role in normal cell growth and differentiation, and is involved in tumour proliferation and survival. EGFR overexpression is a common feature in solid malignancies, including non-small-cell lung cancer (NSCLC), and is associated with poor clinical prognosis. Erlotinib is a small-molecule inhibitor of EGFR tyrosine kinase, showing a significant improvement in median survival, quality of life and related symptoms in an unselected population of advanced NSCLC patients in the second- or third-line setting.

Cisplatin plus gemcitabine or vinorelbine for elderly patients with advanced non small-cell lung cancer: the MILES-2P studies.

Purpose: Two phase I/II trials were done to evaluate the feasibility of cisplatin combined with gemcitabine or vinorelbine in elderly patients with advanced non-small-cell lung cancer (NSCLC).

Patients And Methods: Patients with advanced NSCLC who were older than 70 years of age and who had a performance status of 0 to 1 were eligible. Cisplatin was given on day 1 (a starting dose of 50 mg/m2 with increasing increments of 10 mg/m2 at each level) and gemcitabine (1,000 mg/m2) or vinorelbine (25 mg/m2) on days 1 and 8.

Three cases of long-lasting tumor control with erlotinib after progression with gefitinib in advanced non-small cell lung cancer.

Introduction: We report the cases of three patients with advanced non-small cell lung cancer responding to erlotinib after progression under gefitinib treatment.

Methods: Three never-smoker women with advanced lung adenocarcinoma, two pretreated with chemotherapy and with gefitinib and one with gefitinib alone, received erlotinib in a daily dose of 150 mg. All three patients had disease progression and had achieved tumor control with gefitinib.

A randomized phase II study of sorafenib/gemcitabine or sorafenib/erlotinib for advanced non-small-cell lung cancer in elderly patients or patients with a performance status of 2: treatment rationale and protocol dynamics.

Herein, we present a randomized phase II trial enrolling elderly patients or patients with a performance status (PS) of 2 affected by advanced non-small-cell lung cancer to receive, as first-line therapy, sorafenib/gemcitabine or sorafenib/erlotinib. The primary objective is 1-year survival, and secondary objectives include activity, toxicity, and overall survival. An additional secondary objective will be to evaluate biomarkers.

Informal caregiving burden in advanced non-small cell lung cancer: the HABIT study.

Introduction: This study's aim was to assess economic data regarding the home assistance burden for advanced non-small cell lung cancer (NSCLC) patients in Italy.

Patients And Methods: One hundred four NSCLC patients in second-line chemotherapy (2LC) or in supportive therapy (ST) were enrolled in 18 Italian oncology departments and were observed for 3 months. The main caregiver's workload was assessed monthly by a task scale; other caregivers' activities were also registered.

Lung cancer in the elderly.

Purpose: Elderly patients often have comorbidities and other characteristics that make the selection of treatment daunting.

Methods: We have reviewed the available evidence in the literature to gauge the results of therapy for elderly lung cancer patients.

Results: The beneficial results achieved with adjuvant chemotherapy in the general population with early non-small-cell lung cancer (NSCLC) cannot be automatically extrapolated to the elderly, who are at higher risk of toxicity.

Single-agent pemetrexed or sequential pemetrexed/gemcitabine as front-line treatment of advanced non-small cell lung cancer in elderly patients or patients ineligible for platinum-based chemotherapy: a multicenter, randomized, phase II trial.

Introduction: This randomized phase II trial evaluated single-agent pemetrexed or sequential pemetrexed/gemcitabine in patients with non-small cell lung cancer (NSCLC) who were elderly (> or = 70 years) or younger than 70 years and ineligible for platinum-based chemotherapy.

Methods: Chemonaive patients with stage IIIB/IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 2 received either 500 mg/m2 of pemetrexed (day 1, every 3 weeks) for eight cycles, or the same dosage of pemetrexed for cycles 1 and 2 and then 1200 mg/m2 of gemcitabine (days 1 and 8, every 3 weeks) for cycles 3 and 4 (repeated once for a total of eight cycles). All patients were given vitamin B12 and folic acid supplementation.

A Herpes simplex virus-1 fatal encephalitis following chemo-radiotherapy, steroids and prophylactic cranial irradiation in a small cell lung cancer patient.

Approximately 20-25% of patients with limited small cell lung cancer (SCLC) can be cured with an aggressive approach (chest radiation concomitant with chemotherapy) followed by prophylactic cranial irradiation (PCI) to a total dose of 30-36Gy with 3-2Gy per fraction, five fractions per week. Steroid prophylactic therapy with dexamethasone is usually prescribed during PCI to minimize acute radiation induced brain oedema. This approach may induce an immunosuppressive condition leading to a reactivation of an endogenous latent Herpes simplex virus and severe or fatal acute encephalitis may occur as our report will show.

Role of colony stimulating factors (CSFs) in solid tumours: results of an expert panel.

Febrile neutropenia is a relatively frequent event in cancer patients treated with chemotherapy. A relevant body of scientific evidence has been produced in the last 2 decades, through clinical trials addressing the efficacy of colony stimulating factors (CSFs) in the prevention and treatment of febrile neutropenia. The correct use of CSFs needs to be optimized, and several guidelines have been produced and periodically updated, in order to uniform and guide clinical practice.

Sorafenib and sunitinib in the treatment of advanced non-small cell lung cancer.

Despite the optimization of chemotherapy regimens, treatment outcomes for advanced non-small cell lung cancer (NSCLC) are still considered to be disappointing. Thus, clinical research of new treatment strategies is warranted. Several targeted agents have been introduced into clinical trials in NSCLC, but to date, only a few of these new agents can offer hope of a substantial impact on the natural history of the disease.

Adjuvant chemotherapy in elderly patients with non-small-cell lung cancer.

Background: More than two thirds of patients who die of lung cancer in the United States are over 65 years of age. More than 50% of lung cancer patients are diagnosed over the age of 65 and about 30% over the age of 70.

Methods: The authors review recent data from large randomized trials on adjuvant chemotherapy in patients with NSCLC.

New antiangiogenetic agents and non-small cell lung cancer.

New blood vessel formation, known as angiogenesis is a fundamental event in the process of tumor growth and metastatic dissemination. Due to its central role in tumor angiogenesis, the vascular endothelial growth factor (VEGF) and its receptor have been a major focus of basic research and drug development in the field of oncology, including the treatment of non-small cell lung cancer (NSCLC). Approaches targeting VEGF include monoclonal antibodies and vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs).

Chemotherapy of advanced NSCLC in special patient population.

The elderly and patients with Performance Status (PS) of 2, constitute the so-called special patient population. The tolerability of chemotherapy in this population is globally worse, and treatment approaches should be different. Platinum-based combination chemotherapy is currently recommended as the standard treatment for patients with advanced non-small-cell lung cancer (NSCLC), but its role in special patient population is controversial.