Treatment Of Nonsmall-cell Cancer Research Articles

Cost-effectiveness of pemetrexed in combination with cisplatin as first line treatment for patients with advanced non-squamous non-small-cell lung cancer in Spain

IntroductionLung cancer is the third most frequent neoplastic tumour in Spain, with around 27 000 new cases diagnosed per year; 80-95% of these are non-small-cell cancer (NSCLC), and the majority of cases are diagnosed in advanced stages of the disease, and for this reason it is one of the oncologic conditions with higher mortality rates (21.4% mean survival at 5 years).The main treatment regimens used for first-line treatment of NSCLC are: cisplatin/pemetrexed (cis/pem), cisplatin/gemcita- bine/bevacizumab (cis/gem/bev), and carboplatin/paclitaxel/ bevacizumab (carb/pac/bev). The objective of this study was to evaluate the cost-effectiveness ratio of antineoplastic 1st line NSCLC treatment regimens, from the point of view of hospital management. MethodologyA cost-efficacy mathematical model was prepared, based on a decision tree. The efficacy variable was Progression Free Survival, obtained from the PARAMOUNT, AVAIL and SAIL Phase III clinical trials. The study was conducted from the perspective of the hospital management, considering only the direct costs of drug acquisition. A deterministic sensitivity analysis was conducted to confirm the robustness of outcomes. ResultsThe PFS obtained in clinical trials with cls/pem, cis/ gem/bev and carb/pac/bev was: 6.9, 6.7 and 6.2 months, respectively. Based on our model, the mean cost of treatment per patient for these regimens was: 19942€, 15594 € and 36095€, respectively. The incremental cost-effectiveness ratio per month of additional PFS between cls/pem and cls/gem/bev was 19303€. Estimating a 30% reduction in acquisition costs for pemetrexed (Alimta®Eli Lilly Nederland B.V.), due to the forthcoming launch of generic medications, the cis/pem treatment would become the predominant alternative for 1st line treatment of NSCLC patients, by offering the best health results at a lower cost.

Carbon ion radiotherapy in the management of non‐small cell lung cancer

AbstractDespite advancements in local‐regional and systemic therapies, non‐small cell cancer (NSCLC) remains a leading cause of death worldwide. Among those treated with standard‐of‐care modalities, 30–60% experience disease recurrence. Carbon ion radiotherapy (CIRT) is a form of densely ionizing radiotherapy with unique physical and biological advantages over traditional photon and proton modalities. CIRT is expected to have a superior biological impact on tumors, and is believed to be less impacted by the presence of tumor hypoxia or cell cycle state. It also shows highly conformal physical dose deposition due to reduced lateral scattering of the particles, limiting the radiation dose delivered to adjacent organs at risk. To implement CIRT as a viable option in the treatment of NSCLC, technical aspects of treatment delivery – including appropriate beam arrangements, dose calculation algorithms, radiobiological models, and methods of motion management – must be thoroughly investigated. Furthermore, randomized clinical trials comparing CIRT versus traditional radiation modalities must be performed to show the benefits and risks associated with this novel treatment modality. This review discusses the rationale for utilizing CIRT in NSCLC, available clinical data to date, and the potential for future investigations that may pave the path for improving outcomes in those diagnosed with NSCLC.

The deubiquitinase OTUD1 inhibits non-small cell lung cancer progression by deubiquitinating and stabilizing KLF4.

BackgroundLung cancer results in the highest mortality associated with cancer worldwide. Non‐small cell cancer (NSCLC) is the leading subtype of lung cancer. Ovarian tumor protease (OTU) domain‐containing protein 1 (OTUD1) is a member of the OTU subfamily of DUBs, and its function in NSCLC remains unclear.MethodsGEPIA database was employed to reveal the expression level of OTUD1 in addition to Krüppel‐ like factor 4 (KLF4) in NSCLC tissue samples and prove the correlation between OTUD1 and KLF4. The protein level was estimated using western blot. Cell counting kit‐8 (CCK‐8) assay was used to detect cell viability and transwell assay was utilized to observe cell migration and invasion. Cycloheximide (CHX) was introduced to measure half‐lives of KLF4 and deubiquitination assay was used to detect deubiquitination ability of OTUD1.ResultsOTUD1 expression was downregulated in NSCLC tissues and cells. Overexpression of OTUD1 inhibited NSCLC cell progression and it was promoted by knockdown of OTUD1. OTUD1 was positively correlated with KLF4 and stabilized KLF4 at protein level by deubiquitinating KLF4. Overexpressing KLF4 dramatically eliminated the effects of OTUD1 on the development of NSCLC cells.ConclusionsOur study revealed that OTUD1 suppresses NSCLC progression by mediating KLF4 stabilization, which suggests a potential gene target for the future treatment of NSCLC.

Clinical cases of pembrolisumab immunotherapy treatment in patients with non-small lung cancer with high level of PD-L1 expression in fist line therapy

In Russian Federation, lung cancer is the most frequently diagnosed malignant tumor among men and the fourth in the structure of morbidity among women, also occupying a leading position in the structure of mortality [1]. Non-small cell cancer (NSCLC) accounts for about 80 % of all lung tumors. In turn, in the structure of NSCLC, the most common types are adenocarcinoma (50 %) and squamous cell lung cancer (30 %). The appearance of drugs based on blocking immune checkpoints, in particular PD-1 and PD-L1, has changed the approach to the treatment of NSCLC. Currently, the determination of the optimal tactics for treatment tumors without activated mutations is based on predicting the sensitivity of the tumor to immunotherapy. Evaluation of PD-L1 expression makes it possible to divide patients with NSCLC into several groups of the level of sensitivity to modern immune checkpoint inhibitors. Thus, three groups are distinguished: with negative (≤ 1 %), intermediate (1–49 %) and high (≥ 50 %) expression of PD-L1. The latter includes 23–28 % of patients with advanced NSCLC, regardless of the histological form of the tumor [3]. There are also reasons to believe that in the near future a subgroup of patients with ultra-high expression (> 75 %) PD-L1 will be identifid, in which it is expected to achieve the maximum advantage from treatment with monoimmunotherapy. Pembrolizumab was approved for the treatment of advanced NSCLC with high level of PD-L1 expression (≥ 50 %) with the absence of EGFR / ALK mutations in the fist line of therapy following the publication of the results of the randomized phase III clinical trial KEYNOTE-024. In this study, the median overall survival in the pembrolizumab monotherapy arm was 30.0 months compared with 14.2 months with standard platinum-containing therapy [5]. These data formed the basis for the registration of the fist cytostatic-free regimen in patients with NSCLC without activating mutations. The subsequent study KEYNOTE-042 was an attempt to assess the effect of pembrolizumab in a wider group of patients – with a positive level of PD-L1 expression (PD-L1 ≥ 1 %; ≥ 20 %; ≥ 50 %). In general, the results of the study were positive, but many authors drew attention to the fact that the greatest effect of monoimmunotherapy with pembrolizumab is obtained by patients with a high level of PD-L1 expression. Median overall survival in this study was 20.0 months in the pembrolizumab group and 12.2 months in the chemotherapy group for all patients regardless of PD-L1 status. In this article two clinical cases of the use of the PD-L1 inhibitor pembrolizumab in patients with non-small cell lung cancer and high levels of PD-L1 expression are presented.

PROTON RADIATION THERAPY: CLINICAL APPLICATION OPPORTUNITIES AND RESEARCH PROSPECTS

This article is the review of literature concerning use of proton beam therapy in treatment of oncology. The staticized data on comparison of effi ciency of this method at an eye melanoma are lit. Advantages of proton therapy on the level of local control and depression of frequency of development of the radio induced cataract are refl ected in the provided data. In evident material the technology of preparation and carrying out radiation of an eye is shortly covered with a fascicle of protons. The experience of use of proton therapy of tumors of a skull base got for the last several decades, showed good results. Physical properties of a fascicle of protons allow to achieve the maximum dose conformality, having lowered, thereby, a radial load on the next crucial anatomical structures. The presented material on an oncopediatrics shows insuffi cient knowledge of scientists concerning advantage of a fascicle of protons over modern methods of photon radiation. There are only preliminary clinical results concerning generally of treatment of cranyopharyngiomas. At cancer therapy of a mammary gland, proton therapy showed the best local control of postoperative recurrent tumors, and also depression of a dose load on the contralateral party. The available results of the retrospective analysis of clinical data in the University medical center of Lome Linda, testify to advantages of proton therapy of the localized prostate cancer. The lack of a biochemical recurrence and a local tumoral progression within 5 years after radiation was shown. The data obtained from experience of use of proton radiation therapy with passively scattered fascicle for cancer therapy of a prostate at an early stage showed the admixed results in comparison with modern methods of radiation therapy with the modulated intensity. In treatment of non-small cell cancer of mild advantage of proton therapy aren’t absolutely proved yet. There are data on extreme toxicity of a combination of a chemotherapy and photon radiation. It is supposed that physical properties of protons will allow to reduce toxicity of such technique, however clinical trials in comparison of protons and RTMI aren’t fi nished yet. The main directions of development of a method of proton therapy are shortly lit.

Acquired resistance mechanisms of EGFR-TKI in advanced non-small cell lung cancer

Since the development of molecular biology, the treatment of advanced non-small cell cancer is shifting from traditional chemotherapy into molecular targeted therapy with genotyping as a guide′s help. The most widely used is epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). With the application of EGFR-TKIs, the resistances to EGFR inhibitors are paid more and more attention, in recent years. The main mechanisms of acquired resistances are as follows: secondary mutation of the EGFR gene, amplification of c-MET, Her2 and other target genes, histological transformation, activation of the bypass mechanisms, loss of p53, the relief of negative feedback loops, overlap of mechanisms, etc. Key words: Carcinoma, non-small-cell lung; Drug resistance, neoplasm; Molecular targeted therapy

Present trends in the treatment of advanced non small-cell lung cancer.

Lung cancer is the leading cause of cancer deaths all over the world. As most patients present with advanced disease, major efforts have been made in the treatment of such disease with systemic chemotherapy. Several new agents and new combinations of chemotherapy have been developed recently. This article reviews the randomized clinical trials investigating chemotherapy for advanced non small-cell lung cancer (NSCLC) in relapse or progressive disease while being treated and in elderly patients. Therapies that incorporate new biological agents to target specific defects in lung cancer are also discussed. Several clinical trials have demonstrated improvement in overall survival as well as quality of life with presently available chemotherapy treatment of advanced NSCLC. Better options are available for the elderly as well as those having relapse after first-line chemotherapy. Despite all this progress the 5-year survival rate still remains at a dismal 14%. New therapies with good results are still desired.

Is preoperative or postoperative radiation therapy indicated in non-small cell cancer of the lung?

Induction radiotherapy has no routine indication in the treatment of non-small cell cancer of the lung. No survival benefit has ever been shown in a properly conducted trial. Rarely it might be used prior to attempted complete resection of a tumour in close association with a vital organ, in the hopes of minimising damage to that organ. In combination with chemotherapy, irradiation may eventually find a role within an effective induction regimen, particularly in IIIA disease. Post-operative irradiation will reduce local-regional relapse rates in completely resected disease, but there is no demonstrable survival benefit. In incompletely resected disease, usually more advanced initially, there may be a similar effect, of smaller magnitude. However such patients are usually at greater risk from systemic relapse. The availability of radiotherapy should not encourage surgeons to use anything less than meticulous and consistent selection procedures; patients who are technically unresectable should be submitted for experimental protocols, or standard treatment with exclusive radiotherapy.