Meta-analysis of single-agent chemotherapy compared with combination chemotherapy as second-line treatment of advanced non-small-cell lung cancer.

Purpose: Doublet chemotherapy is more effective than single-agent as first-line treatment of advanced non-small-cell lung cancer (NSCLC). As second-line treatment, several randomized trials have been performed comparing single-agent with doublet chemotherapy, but each trial had an insufficient power to detect potentially relevant differences in survival.

Methods: We performed meta-analysis of individual patient data from randomized trials, both published and unpublished, comparing single-agent with doublet chemotherapy as second-line treatment of advanced NSCLC.

A "live" biopsy in a small-cell lung cancer patient by detection of circulating tumor cells.

A 71-year-old patient with a pulmonary lesion was diagnosed with a low-grade neuroendocrine tumor following examination of a fine needle aspiration biopsy. Analysis of a peripheral blood sample with the CellSearch system revealed the presence of putative circulating tumor cells (CTC) that were positive for EpCAM and cytokeratin (CK) expression. Since EpCAM is not usually expressed in neuroendocrine tumors, we performed a biopsy of liver metastases.

Second and third line treatment in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide, and the advances in second and third line treatment have led to prognostic improvements in the latest years. Besides the two cytotoxic agents, docetaxel and pemetrexed, approved in NSCLC second line treatment, a new class of drugs against specific molecular targets seems to be an alternative to conventional treatment. Many trials are ongoing to assess the activity of new drugs, alone or in association, and new combinations of third-generation chemotherapeutic agents.

Potential treatment options after first-line chemotherapy for advanced NSCLC: maintenance treatment or early second-line?

Although substantial progress has been made in the therapeutic options currently available for patients with advanced non-small cell lung cancer (NSCLC), the overall survival profile remains poor for most patients. One of the strategies currently under investigation with the aim of prolonging survival in NSCLC patients is maintenance treatment with either a chemotherapeutic agent or a molecularly targeted agent after first-line chemotherapy. Moreover, this can consist of drugs included in the induction regimen or other noncrossresistant agents.

Biological prognostic and predictive factors in lung cancer.

The inclusion of new drugs in clinical research and practice has allowed improvements in several outcomes of advanced non-small-cell lung cancer (NSCLC). Among these drugs, very interesting results have been obtained from pemetrexed and new targeted agents, including the inhibitors of epidermal growth factor receptor (EGFR) such as gefitinib, erlotinib and cetuximab. Unfortunately, these new drugs when investigated for the treatment of small-cell lung cancer (SCLC) reported negative results.

New avenues for second-line treatment of metastatic non-small-cell lung cancer.

Platinum-based doublets are the standard first-line therapy for patients with advanced non-small-cell lung cancer, with approximately a third of patients obtaining an objective response with first-line chemotherapy and another 20-30% achieving temporary disease stabilization. However, all patients inevitably experience disease progression. Three agents are approved for treating patients who progress after one prior regimen: docetaxel, pemetrexed and erlotinib.

An expanded access program of erlotinib (Tarceva) in patients with advanced non-small cell lung cancer (NSCLC): data report from Italy.

Background: Erlotinib demonstrated significantly prolonged survival versus placebo in patients with advanced NSCLC who had progressed after standard chemotherapy. TRUST is a phase IV trial initiated to provide erlotinib access to patients with advanced NSCLC. We report the interim analysis for patients enrolled in the TRUST trial in Italy.

New targeted therapies and small-cell lung cancer.

Small-cell lung cancer (SCLC) accounts for almost 15% of lung carcinomas. Chemotherapy is the cornerstone of treatment of patients with SCLC. In limited disease, median survival is about 12-20 months, with no more than 6%-12% of patients surviving beyond 5 years.

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.

The MILES-2G phase 2 study of single-agent gemcitabine with prolonged constant infusion in advanced non-small cell lung cancer elderly patients.

Background: Gemcitabine has been widely studied in elderly patients affected by advanced non-small cell lung cancer (NSCLC). A prolonged constant infusion (10 mg/m2/min) has been proposed as a way to improve its efficacy. Aim of this study is to describe activity and toxicity of single-agent gemcitabine given as prolonged infusion in the treatment of elderly patients with advanced NSCLC.

An international, multicenter, randomized phase III study of first-line erlotinib followed by second-line cisplatin/gemcitabine versus first-line cisplatin/gemcitabine followed by second-line erlotinib in advanced non-small-cell lung cancer: treatment rationale and protocol dynamics of the TORCH trial.

Herein, we present a randomized phase III Italian-Canadian trial named TORCH (Tarceva or Chemotherapy). In TORCH, we are investigating whether erlotinib as first-line therapy until progression followed by chemotherapy with cisplatin/gemcitabine will not be inferior in terms of survival to the standard arm, consisting of first-line cisplatin/gemcitabine for 6 cycles, followed at progression by erlotinib until second progression. The primary objective is overall survival, and an adjunctive primary endpoint is activity of first-line treatment with erlotinib in terms of progression-free rate after 9 weeks of treatment.

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.

Weekly docetaxel vs. docetaxel-based combination chemotherapy as second-line treatment of advanced non-small-cell lung cancer patients. The DISTAL-2 randomized trial.

Background: Doublet chemotherapy is more effective than single-agent as first line treatment of advanced non-small-cell lung cancer (NSCLC). No reliable information instead is available on the effect of doublets in second line treatment. The aim of DISTAL-2 study was to compare two doublets containing docetaxel with single agent docetaxel as second line treatment of patients with NSCLC (ClinicalTrials.

Sequence-dependent, synergistic antiproliferative and proapoptotic effects of the combination of cytotoxic drugs and enzastaurin, a protein kinase Cbeta inhibitor, in non-small cell lung cancer cells.

Enzastaurin, an acyclic bisindolymaleimide, is a potent and selective competitive inhibitor of protein kinase Cbeta, which has been shown to inhibit cancer cell proliferation and angiogenesis in human cancer cell lines. Gemcitabine and pemetrexed are two cytotoxic drugs that are currently used in non-small cell lung cancer (NSCLC) therapy. In this study, we have investigated whether the addition of enzastaurin to gemcitabine or to pemetrexed is able to increase their antitumor activity to establish an effective schedule of combined treatment.

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.

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.

Identifying an optimum treatment strategy for patients with advanced non-small cell lung cancer.

Owing to the slow but sustained progress made in lung cancer treatment over the last 20 years, several therapeutic options are now available in the first-line setting as well as for patients who have progressed after one or more previous lines of treatment. Considering the growing array of choices currently confronting clinicians involved in the treatment of advanced non-small cell lung cancer (NSCLC), an effort should be made to define the optimal treatment option in each disease setting and to identify a logical therapeutic strategy after initial disease progression. This is especially crucial in the management of young, fit patients, who may be suitable candidates for two or more lines of therapy.

Vulnerable and frail elderly: an approach to the management of the main tumour types.

In dealing with older cancer patients undergoing chemotherapy, some form of geriatric evaluation is needed to distinguish those which can be treated as adults from those - the vulnerable ones - who need a modified approach and also from those who are frail or too sick to receive an active treatment. Only scarce data are available to guide treatment of vulnerable or frail patients, the neglected majority of older cancer patients. In most of these cases they receive an adapted approach which does not derive from the results of clinical trials, but from an enlightened empiricism.

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.