Regional chemotherapy was first used for lung cancer 30 years ago. Since then, new methods of drug delivery and pharmaceuticals have been investigated in vitro, and in animals and humans. An extensive review of drug delivery systems, pharmaceuticals, patient monitoring, methods of enhancing inhaled drug deposition, safety and efficacy, and also additional applications of inhaled chemotherapy and its advantages and disadvantages are presented. Regional chemotherapy to the lung parenchyma for lung cancer is feasible and efficient. Safety depends on the chemotherapy agent delivered to the lungs and is dose-dependent and time-dependent. Further evaluation is needed to provide data regarding early lung cancer stages, and whether regional chemotherapy can be used as neoadjuvant or adjuvant treatment. Finally, inhaled chemotherapy could one day be administered at home with fewer systemic adverse effects.

Lung cancer first line treatment has been directed from the non-specific cytotoxic doublet chemotherapy to the molecular targeted. The major limitation of the targeted therapies still remains the small number of patients positive to gene mutations. Furthermore, the differentiation between second line and maintenance therapy has not been fully clarified and differs in the clinical practice between cancer centers. The authors present a segregation between maintenance treatment and second line and present a possible definition for the term “maintenance” treatment. In addition, cancer cell evolution induces mutations and therefore either targeted therapies or non-specific chemotherapy drugs in many patients become ineffective. In the present work pathways such as epidermal growth factor, anaplastic lymphoma kinase, met proto-oncogene and PI3K are extensively presented and correlated with current chemotherapy treatment. Future, perspectives for targeted treatment are presented based on the current publications and ongoing clinical trials.

Background:The emergence of novel antiprogrammed cell death protein-1 (PD-1) inhibitors in non-small cell lung cancers (NSCLC) has revolutionized the therapeutic landscape of this disease. Although overall survival (OS) has improved in the first- and second-line therapy settings for advanced NSCLC, the benefit is not universal. In a climate of global scrutiny for healthcare costs and potential for toxicities related to immunotherapy, appropriate patient selection is crucial. The aim of this study was to evaluate potential prognostic and predictive biomarkers interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and a panel of interleukins (ILs) in the peripheral blood, and assess any correlation with response to anti-PD-1 inhibition, progression-free survival and OS in NSCLC patients.Methods:We prospectively studied 26 NSCLC patients that received immunotherapy (either pembrolizumab or nivolumab). IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10 and IL-12 were analyzed by flow cytometry at the time of diagnosis and at 3 months after initiation of anti-PD-1 inhibition.Results:Increased cytokine values (IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6 and IL-8) at the time of diagnosis and at 3 months after initiation of treatment were significantly correlated with improved response to immunotherapy and prolonged OS. There was no correlation between cytokine levels and programmed cell death ligand-1 (PD-L1) expression.Conclusions:Increased IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10 and IL-12 levels resulted in better response to NSCLC anti-PD-1 inhibition and longer survival, and this could potentially play an important role in selecting patients that would benefit from anti-PD-1 inhibitors.

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