The role of epidermal growth factor receptor in advanced non‐small cell lung carcinoma

Chemotherapy is the standard of care for patients with advanced non‐small cell lung cancer (NSCLC). Over the past 20 years, advances in chemotherapy have shown minimal incremental improvement in the survival outcomes of patients with advanced NSCLC. With the identification of molecular and genetic alterations in lung cancer, several new potential rationally designed therapeutic targets have emerged. One of these is the epidermal growth factor receptor (EGFR) and member of the ErbB family of receptor tyrosine kinases. Several inhibitors, both antibodies directed at the extra‐cellular portion of the receptor, and small molecule inhibitors directed at the tyrosine kinase domain of EGFR are in clinical development in lung cancer. This article will review the pre‐clinical rationale and the clinical studies of EGFR inhibitors alone and/or in combination with chemotherapy that have been performed to date in advanced NSCLC.     

Is leptin a predictive factor in patients with lung cancer?

Objectives

The aim of this study was to evaluate the expression and clinical significance of leptin in lung cancer.

Methods

126 patients with lung cancer ranged from 30 to 83 years of age were studied. Serum leptin levels were determined by ELISA. The mRNA and protein levels of leptin in normal and lung cancer tissues were measured by RT-PCR and immunohistochemistry. The relationships between leptin levels and clinicopathological factors were evaluated by Wilcoxon rank sum or Kruskal–Wallis H test.

Results

Serum leptin levels in lung cancer patients were significantly higher compared to those in controls and leptin expression in lung cancer tissue was markedly increased than that in normal lung tissue (both P < 0.050).

Conclusions

Determination of leptin levels might provide useful predictive information for lung cancer.     

Is the presence of dyspnea a risk factor for morbidity in cancer patients?

Data collected from six home palliative care teams in Ireland were analyzed to determine the prevalence of dyspnea in the population studied and to identify factors associated with the presence of dyspnea that might impact on future care. The prevalence of mild, moderate, or severe dyspnea, as measured by the Support Team Assessment Schedule (STAS), fell from 39% at referral in 327 evaluable patients to 23%. The presence of dyspnea at referral was positively correlated with severity of patient spiritual distress (Spearman rho = 0.110, P = 0.042) and weakness (Spearman rho = 0.105, P = 0.008) at referral. In analysis of contingency tables, dyspnea was also significantly associated with low patient (chi 2 9.5, P = 0.002) and family (chi 2 50.78, P < 0.001) well-being, high staff anxiety (chi 2 4.14, P = 0.04), male sex (chi 2 8.9, P = 0.003), a diagnosis of lung cancer (chi 2 59.88, P < 0.001), and dying in hospital rather than hospice or nursing home (chi 2 18.03, P = 0.001). In adjusting for covariates using a logistic regression analysis, however, only the presence of low family well-being, a diagnosis of lung cancer, and increased likelihood of a hospital death remained significantly associated with the presence of dyspnea at referral. These data suggest that the presence of dyspnea may be associated with increased family distress, which may influence place of death.     

Is there still a role for open cordotomy in cancer pain management?

For a small number of cancer patients, good pain control remains difficult to achieve despite adequate assessment and medical management. In nine cases, effective control of intractable pain from malignant pelvic disease was achieved by open thoracic cordotomy. The technique was well tolerated, with no major complications. Eight of the nine patients decreased their median daily oral morphine requirement from 560 mg (range 360-2600 mg) to 160 mg (range 40-1000 mg). Maximal survival time post-cordotomy was 830 days, with a median of 107 days. No patient experienced recurrent pain in the initially painful site. For patients with intractable pain associated with advanced pelvic malignancy, the use of an open cordotomy should be considered when satisfactory pain control is not achieved by medical or minimally invasive methods.     

Is there progress in chemotherapy for breast cancer?

Breast cancer is the most frequent type of cancer in women. The therapeutic approaches to breast cancer have developed rapidly over the past 20 years, due to the increasing knowledge about the biology of breast cancer. Therefore it was possible to increase response rates as well as the duration of response and survival in neoadjuvant, adjuvant, and palliative treatment. This paper gives a review of the current breast cancer trials. Effective new cytotoxic chemotherapy and hormonal therapy agents, as well as the identification of specific molecular abnormalities (HER2/neu) led to the development of targeted therapeutic interventions in the neoadjuvant, adjuvant, and palliative treatment of breast cancer. Increased understanding of the biology of breast cancer led to the development of rational therapeutic interventions, which are currently under active clinical development.     

Is there still a role for abatacept in the treatment of lupus?

Introduction: The quest for safer and more effective treatments for systemic lupus erythematosus (SLE) has led to the development of many new biologic therapies. Abatacept is the first drug targeting co-stimulation between T cells and antigen presenting cells, with abundant pre-clinical evidence to support its use in SLE.

Areas covered: This review will present the relevant aspects of lupus pathophysiology pertaining to the mechanism of action of abatacept, a summary of murine studies and the latest human clinical trials.

Expert opinion: Abatacept has demonstrated efficacy in both rheumatoid arthritis and psoriatic arthritis, and earlier studies have suggested tantalising evidence of efficacy in SLE. However, the latest randomised double-blinded study showed disappointingly negative results, much like the case of rituximab in SLE. Currently, abatacept remains a possible therapeutic option as an off-label therapy, and it is a part of our therapeutic armamentarium in difficult cases. The need to find appropriate definitions of response and optimal study design continues to be paramount in the field of lupus therapies.     

Is there still a role for sucralfate in the treatment of gastritis?

The endoscopic diagnosis of gastritis is usually made when a patient develops symptoms and undergoes an upper gastrointestinal endoscopy. There are often obvious aetiological causes such as smoking, alcohol Helicobacter pylori infection or drug treatment. Lifestyle changes can sometimes improve symptoms but often patients will be treated with a proton pump inhibitor. The stomach mucosa produces a protective mucous to prevent damage cause by gastric acid and exogenous agents can disrupt this layer. Repair of this protective layer can be enhanced by reduction in gastric acid secretion using H2 receptor antagonist or proton pump inhibitors or by cytoprotective drugs such as misoprostol, sucralfate, aluminium ions or bismuth subsalts. Sucralfate is a complex polymer which at a low pH changes its chemical configuration and binds to serum protein to form a protective layer protecting the mucosa against further injury. Cytoprotective drugs were the first line treatment for peptic disease including gastritis for many years but since the launch of cimetidine in 1976 and the subsequent launch of omeprazole in 1988, their use has slowly declined. First line treatment for patients with symptomatic gastritis after removal of potential causative factors is likely to be a proton pump inhibitor in 2019. This is despite the fact that there is some evidence that sucralfate is superior than a H2 receptor antagonist in the endoscopic healing rates in patients with gastritis. The logical treatment choice in patients with resistance symptoms is a combination of a proton pump inhibitor and sucralfate but evidence is lacking. Until such evidence is available In the meantime, we would suggest that there is a role for sucralfate in the treatment of intransigent gastritis and that mucosal protection should be considered even ahead of acid suppression given its favourable safety and toxicity profile.     

Is there a place for granulocyte colony-stimulating factor in non-neutropenic critically ill patients?

Immunoparalysis, characterised by impairments in neutrophil and monocyte/macrophage function, is common in critically ill patients. The theoretical ability of granulocyte colony-stimulating factor (G-CSF) to improve the functions of both neutrophils and monocytes/macrophages provides a rationale for G-CSF therapy in non-neutropenic critically ill patients with infection or a high risk of nosocomial infection. The expression of the receptors that mediate G-CSF effects in neutrophils and monocytes/macrophages is regulated by bacterial products, cytokines and endogenous G-CSF levels, accounting for the variables effects of G-CSF on the neutrophil functions of critically ill patients. This variability should be taken into account when designing studies on the use of G-CSF in ICU-patients. Studies are still needed to identify the subset of patients who may benefit from G-CSF therapy.     

Can plasma DNA monitoring be employed in personalized chemotherapy for patients with advanced lung cancer?

Personalized chemotherapy is the ideal treatment usually chosen to help improve the survival chances of patients with advanced lung cancer. However, there is no short-term evaluation protocol for predicting the efficacy of the therapy. The aim of this study was to determine the value of using plasma DNA to monitor chemotherapeutic efficacy and to select most appropriate chemotherapeutic regimen for patients with advanced lung cancer. Eighty-eight lung cancer patients and 200 healthy controls were included in this study. Plasma DNA was extracted from plasma samples with internal controls by using the BILATEST DNA Kit. The quantity of plasma DNA was determined by using duplex real-time quantitative PCR. After first-line chemotherapy, plasma DNA levels of partial response patients were significantly different from those of stable disease patients or progressive disease patients, but with no statistical difference from healthy controls (P = 0.014, P < 0.001 and P = 0.418, respectively). Survival analysis showed a statistically better survival time in patients who had lower levels of plasma DNA after the third cycle chemotherapy (P = 0.031). In this study, the correlation of the kinetics of DNA concentrations with chemotherapeutic efficacy during the whole therapy was also observed. The quantification of plasma DNA is a sensitive indicator of chemotherapeutic efficacy in advanced lung cancer patients, and it can be useful in predicting response to therapy and guiding medication.     

Is there a case for paternalism in forensic nursing?

Forensic nurses often face a competing duty to patients and society. This article explores possible solutions to the ethical conflict.     

Is there a potential role for attention bias modification in pain patients? Results of 2 randomised,controlled trials

Potential applications of attention bias modification (ABM) for acute and chronic pain patients are investigated. In study 1, 54 acute back pain patients (46 of whom completed the study) were recruited at their initial physiotherapy session and randomised to receive 1 session of ABM or placebo. Patients were followed up 3 months later. Participants who were randomised to receive ABM reported less average (P=0.001) and current pain (P=0.008) and experienced pain for fewer days (P=0.01) than those who received placebo. In study 2, 34 chronic pain patients were recruited and randomly assigned to receive either 4 sessions of ABM (n=22) or placebo (n=12), followed by 8 sessions of cognitive behavioural treatment (CBT). After ABM, there was a significant group-by-time effect for disability. By 6-month follow-up, differences had emerged between the 2 training groups, such that the ABM group had shown greater reductions in anxiety sensitivity and disability than the placebo group. Although the results of these studies show that there is potential in the application of ABM to pain conditions, the mechanisms of treatment could not be established. Neither group showed an initial bias towards the word stimuli or a training effect, and only in the acute pain group were changes in biases related to outcome. Nonetheless, the fact that 2 independent samples showed a positive effect of ABM on clinical outcomes suggests that ABM is worthy of future study as an intervention for pain patients.     

Is there still a future for neurokinin 3 receptor antagonists as potential drugs for the treatment of psychiatric diseases?

Selective non-peptide antagonists for the neurokinin 3 (NK₃) receptor first became available about twenty years ago. Although the understanding of the role of the NK₃ receptor in the brain has been greatly complicated by marked species differences in its distribution and by pharmacological heterogeneity, studies with brain-penetrant non-peptide NK₃ receptor antagonists in animals have indicated that these compounds may find utility in a number of psychiatric diseases, including schizophrenia, anxiety and depressive disorders. However, clinical studies with selective NK₃ receptor antagonists in these psychiatric conditions have been disappointing and they were unable to confirm the promising therapeutic potential from animal studies, thereby questioning the therapeutic utility of these compounds for CNS disorders. The purpose of this article is to provide a critical overview of the available data on NK₃ receptor antagonists in the psychiatry research and development field, by reviewing the behavioral and neurochemical effects of these agents in both preclinical and clinical studies.     

Do internal standards of quality of life change in lung cancer patients?

BACKGROUND: Measurement of health-related quality of life (QOL) over time often yields results that may be difficult to understand. Patients may change their internal standards of QOL as a result of adaptation to deteriorating health, a phenomenon referred to as response shift. OBJECTIVES: To examine changes in internal standards of fatigue, global health/QOL, and physical function in patients with inoperable lung cancer at 3 months (n = 115) and 6 months (n = 89) after a baseline measurement close to diagnosis. Significant changes were expected to occur only in patients who reported improvement or deterioration in fatigue and global health/QOL. METHODS: Fatigue, global health/QOL, and physical function were assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30, version 3.0). At follow-up, this questionnaire was administered conventionally and as a retrospective baseline assessment (thentest). Subjective transition questions were used to form mutually exclusive patient subgroups (i.e., deterioration, stable, or improvement). RESULTS: With respect to fatigue, significant changes occurred in patients reporting deterioration at 3 months follow-up and in patients reporting improvement after 6 months, but not in patients reporting improvement after 3 months or deterioration after 6 months. Significant changes in global health/QOL were found in patients reporting improvement at both 3 and 6 months follow-up and unexpectedly in stable patients after 3 months. No significant changes were found in patients reporting deteriorated global health/QOL at 3 and 6 months. Unexpectedly, changes occurred at both 3 and 6 months in patients reporting improved physical function. DISCUSSION: Given these mixed findings, it cannot be concluded that changes in internal standards occurred. These severely ill patients reported high levels of symptoms at baseline and may in part have adapted to their symptoms before study entry.     

Is lymphadenectomy in stage I of non-seminomatous testicular cancer still justified?

Testicular cancer is the tumour of the male genital tract which is most easily and successfully treated today. This very circumstance dictates that for ethical reasons we are more bound than ever to prevent unnecessary diagnostic and therapeutic procedures in these young patients. They should receive only the maximum necessary and not the maximum possible therapy. The difference between these two critical concepts determines the extent of treatment morbidity. Retroperitoneal lymphadenectomy (RLA) is only a diagnostic procedure in approximately 85% of cases. This is the reason for critically reviewing the necessity of this investigation in early non-seminomatous cancer of the testes. The prognostic impact of vascular invasion by the primary tumour is demonstrated in a retrospective study of 86 pathohistological specimens of germ cell tumours. We suggest the inclusion of vascular invasion basically as criterion for any prospective "wait and see" protocol in early non-seminomatous germ cell tumours.