zithromax and Lung-Neoplasms

Pharmacological targeting aberrant activation of epidermal growth factor receptor tyrosine kinase signaling is an established approach to treating lung adenocarcinoma. Osimertinib is a tyrosine kinase approved and effective in treating lung adenocarcinomas that have one of several common activating mutations in epidermal growth factor receptor. The emergence of resistance to osimertinib after a year or two is the rule. We developed a five-drug adjuvant regimen designed to increase osimertinib's growth inhibition and thereby delay the development of resistance. Areas of Uncertainty: Although the assembled preclinical data is strong, preclinical data and the following clinical trial results can be discrepant. The safety of OPALS drugs when used individually is excellent. We have no data from humans on their tolerability when used as an ensemble. That there is no data from the individual drugs to suspect problematic interaction does not exclude the possibility.. All relevant PubMed.org articles on the OPALS drugs and corresponding pathophysiology of lung adenocarcinoma and glioblastoma were reviewed. Therapeutic Opinion: The five drugs of OPALS are in wide use in general medicine for non-oncology indications. OPALS uses the anti-protozoal drug pyrimethamine, the antihistamine cyproheptadine, the antibiotic azithromycin, the antihistamine loratadine, and the potassium sparing diuretic spironolactone. We show how these inexpensive and generically available drugs intersect with and inhibit lung adenocarcinoma growth drive. We also review data showing that both OPALS adjuvant drugs and osimertinib have data showing they may be active in suppressing glioblastoma growth.

Topics: Acrylamides; Adenocarcinoma of Lung; Aniline Compounds; Animals; Azithromycin; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Chemotherapy, Adjuvant; Cyproheptadine; Drug Repositioning; Drug Resistance, Neoplasm; ErbB Receptors; Glioblastoma; Humans; Loratadine; Lung Neoplasms; Mice; Neoplasm Metastasis; Pyrimethamine; Spironolactone

We have selected four papers which brought major, new contributions to pulmonary medicine over the last year. These publications address following issues: The effect of low-dose CT-screening on lung cancer mortality; treatment of lung emphysema by bronchoscopy with endobronchial valves drainage of pleural infections with combined fibrinolytic agent and desoxyribonuclease; and long-term treatment of COPD with azithromycin. Each of these studies has brought novel and relevant information. It is too early to say that current practice has to be changed following these studies. However, they certainly open from now new diagnostic and therapeutic considerations on a case by case basis.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchoscopy; Deoxyribonucleases; Drainage; Early Detection of Cancer; Emphysema; Empyema, Pleural; Fibrinolytic Agents; Humans; Lung Neoplasms; Mass Screening; Pulmonary Disease, Chronic Obstructive; Pulmonary Medicine; Tomography, X-Ray Computed; Treatment Outcome

Legionella species are a common cause of community-acquired pneumonia, infrequently complicated by cavitary disease. We describe Legionella pneumophila pneumonia and abscess formation in an immunosuppressed patient receiving corticosteroid therapy for metastatic breast carcinoma. The predisposing role of corticosteroids is discussed and the management of this complication is reviewed.

Topics: Adult; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Australia; Azithromycin; Brain Neoplasms; Breast Neoplasms; Ceftriaxone; Combined Modality Therapy; Cranial Irradiation; Dexamethasone; Diagnosis, Differential; Drainage; Female; Humans; Immunocompromised Host; Legionella pneumophila; Legionnaires' Disease; Lung Abscess; Lung Neoplasms; Metronidazole; Roxithromycin; Thoracic Surgery, Video-Assisted; Thoracostomy; Tomography, X-Ray Computed

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiolitis; Chronic Disease; Clarithromycin; Erythromycin; History, 20th Century; Humans; Japan; Lung Neoplasms; Respiratory Tract Infections

Antibiotic concentrations in pulmonary tissue samples and plasma were studied in this open investigation. Twenty-nine patients scheduled for elective pulmonary surgery received a single oral dose of 500 mg azithromycin 24, 72, 96 or 120 h prior to the operation; two patients received 250 mg b.i.d. Blood samples were taken before and at the time of resection, and tissue was obtained during surgery. Plasma and tissue concentrations of azithromycin were measured by high performance liquid chromatography (HPLC) and a microbiological bioassay. Only one patient had a detectable plasma concentration of azithromycin (0.13 micrograms/ml), measured 24 h post-dose by HPLC. However, high and sustained levels were found in lung tissue: mean concentrations measured by HPLC were 3.10 micrograms/g (SD +/- 2.17), 2.55 micrograms/g (SD +/- 1.36), 3.94 micrograms/g (SD +/- 2.40) and 3.13 micrograms/g (SD +/- 0.50) at 24, 72, 96 and 120 h, respectively. Bioassay results were similar to those for the HPLC assay. In summary, azithromycin levels in pulmonary tissue remained close to 3 micrograms/g for up to 5 days after a single oral 500 mg dose, in contrast to plasma levels which were much lower. The lung concentrations found are inhibitory for many sensitive respiratory pathogens and short-course azithromycin therapy is therefore a possibility.

Topics: Administration, Oral; Adult; Aged; Azithromycin; Biological Assay; Carcinoma, Bronchogenic; Chromatography, High Pressure Liquid; Drug Administration Schedule; Erythromycin; Humans; Lung; Lung Neoplasms; Middle Aged

The current use of prophylactic antibiotics for lung cancer surgery requires modification in aging individuals with impaired lung function. A sustained-release formulation of azithromycin (AZM-SR) could help resolve some of these challenges with its sustained antibacterial and anti-inflammatory effects. The aim of this study was to examine the safety and efficacy of AZM-SR in lung cancer surgery as well as its anti-inflammatory effect.. Fifty patients were included in the study, and AZM-SR was administered 1 day prior to the surgery. The clinical course, including postoperative complications, was monitored, and the concentration of AZM, bacterial culture, and inflammatory cytokine levels of resected lung specimens were evaluated.. No side effects related to AZM-SR were observed. Five cases of postoperative pneumonia (10%) were observed; technical issues were involved in 3 cases. All patients recovered well. Four cases showed positive bacterial culture upon lung tissue examination; however, this was not significantly correlated with postoperative complications. A negative correlation was observed between AZM concentration in lung tissue and interleukin-6 (IL-6) expression.. Prophylactic utilization of AZM-SR in lung cancer surgery seems feasible. The anti-inflammatory effect of AZM might contribute additional beneficial effects in the perioperative management of lung cancer surgery.

Topics: Anti-Bacterial Agents; Azithromycin; Delayed-Action Preparations; Humans; Lung; Lung Neoplasms

Cancer cells use autophagy for growth, survival, and cytoprotection from chemotherapy. Therefore, autophagy inhibitors appear to be good candidates for cancer treatment. Our group previously reported that macrolide antibiotics, especially azithromycin (AZM), have potent autophagy inhibitory effects, and combination treatment with tyrosine kinase inhibitors or proteasome inhibitors enhances their anti-cancer activity. In this study, we evaluated the effect of combination therapy with DNA-damaging drugs and AZM in non-small-cell lung cancer (NSCLC) cells. We found that the cytotoxic activities of DNA-damaging drugs, such as doxorubicin (DOX), etoposide, and carboplatin, were enhanced in the presence of AZM in NSCLC cell lines, whereas AZM alone exhibited almost no cytotoxicity. This enhanced cell death was dependent on wild-type-p53 status and autophagosome-forming ability because TP53 knockout (KO) and ATG5-KO cells attenuated AZM-enhanced cytotoxicity. DOX treatment upregulated lysosomal biogenesis by activating TFEB and led to lysosomal membrane damage as assessed by galectin 3 puncta assay and cytoplasmic leakage of lysosomal enzymes. In contrast, AZM treatment blocked autophagy, which resulted in the accumulation of lysosomes/autolysosomes. Thus, the effects of DOX and AZM were integrated into the marked increase in damaged lysosomes/autolysosomes, leading to prominent lysosomal membrane permeabilization (LMP) for apoptosis induction. Our data suggest that concomitant treatment with DNA-damaging drugs and AZM is a promising strategy for NSCLC treatment via pronounced LMP induction.

Topics: A549 Cells; Autophagy; Azithromycin; Carboplatin; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Membrane Permeability; Cell Proliferation; Cell Survival; DNA Damage; Drug Synergism; Humans; Lung Neoplasms; Lysosomes; Topoisomerase II Inhibitors

Outbreak of the new type coronavirus infection, known as coronavirus infection 2019 (COVID-19), has begun in December 2019, in Wuhan, China. As of today, 3 April 2020, 972,640 people affected and 50,325 people died from Severe Acute Respiratory Syndrome-Coronavirus 2. There is not any standard treatment for coronavirus infection 2019; however, there are promising data for hydroxychloroquine and some anti-retroviral drugs. Programmed death-1 (PD-1)/programmed death ligand-1 (PDL-1) pathway is an important target for the cancer immunotherapy. However, there is a robust pre-clinical and clinical data regarding inhibitor effect of this pathway on the acute or chronic viral infections. Thus, blockade of this pathway may lead to an anti-viral effect and decrease viral load. Here, we report the clinical course of coronavirus infection 2019 infection of a patient in whom older aged, having multiple co-morbidities, and taking nivolumab for metastatic malignant melanoma. In contrast to her older age, comorbidities, and cancer diagnosis, she was in a good condition, and there was also no pneumonia finding. We think that this good clinical course of coronavirus infection 2019 infection may be related to blockade of PD-1/PDL-1 pathway with nivolumab. It is impossible to say that blockade of PD-1/PDL-1pathway is a treatment option for COVID-19; however, we want to share our experience.

Topics: Aged; Antineoplastic Agents, Immunological; Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Female; Humans; Hydroxychloroquine; Lung Neoplasms; Melanoma; Multiple Chronic Conditions; Nivolumab; Oseltamivir; Pandemics; Pneumonia, Viral; Programmed Cell Death 1 Receptor; SARS-CoV-2; Tomography, X-Ray Computed; Treatment Outcome

Currently there are no reported series determining the Covid-19 infected lung cancer patient´s characteristics and outcome that allow us to clarify strategies to protect our patients. In our study we determine whether exists differences in cumulative incidence and severity of Covid-19 infection between lung cancer patients visiting our Medical Oncology department and the reference population of our center (320,000 people), in the current epicenter of the pandemic in Europe (Madrid, Spain). We also describe clinical and demographic factors associated with poor prognosis and Covid-19 treatment outcomes.. We retrospectively reviewed 1878 medical records of all Covid-19 patients who were admitted at Hospital Universitario Infanta Leonor of Madrid between March 5, 2020 and April 7, 2020, in order to detect cumulative incidence of Covid-19 in lung cancer patients. We also described Covid-19 treatment outcome, mortality and associated risk factors using univariate and multivariate logistic regression analysis.. 17/1878 total diagnosis in our center had lung cancer (0.9 %) versus 1878/320,000 of the total reference population (p = 0.09). 9/17 lung cancer patients with Covid-19 diagnosis died (52.3 %) versus 192/1878 Covid-19 patients in our center (p < 0.0001). Dead lung cancer patients were elderly compared to survivors: 72 versus 64.5 years old (p = 0.12). Combined treatment with hydroxychloroquine and azithromycin improves the outcome of Covid-19 in lung cancer patients, detecting only 1/6 deaths between patients under this treatment versus others treatment, with statistical significance in the univariate and multivariate logistic regression (OR 0.04, p = 0.018).. Lung cancer patients have a higher mortality rate than general population. Combined hydroxychloroquine and azithromycin treatment seems like a good treatment option. It is important to try to minimize visits to hospitals (without removing their active treatments) in order to decrease nosocomial transmission.

Topics: Aged; Aged, 80 and over; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Cross Infection; Drug Combinations; Female; Humans; Hydroxychloroquine; Logistic Models; Lung Neoplasms; Male; Middle Aged; Pandemics; Pneumonia, Viral; Prognosis; SARS-CoV-2; Spain

Treatment of malignancy with anti-programmed cell death 1 (PD-1) immune checkpoint inhibitors can cause mucocutaneous side effects resulting from T cell activation. Due to their recent development, the full side effect profile remains to be fully elucidated, however dermatologic adverse events are most common. The main oral toxicities of these immune checkpoint inhibitors include: xerostomia, dysgeusia, and lichenoid reactions. Oral mucositis occurs more rarely in the setting of PD-1 inhibition, and few other reports of a Grade 3 or higher, severe, stomatitis have been reported in the literature. We present a case of a 78-year-old woman with Grade 3 ulcerative oral mucositis that occurred 13 months after initiation of PD-1 inhibitor, pembrolizumab, for the treatment for lung adenocarcinoma. She was successfully treated with prednisone, and pembrolizumab was temporarily held by her oncologist. Physicians should be aware of the possibility of severe mucositis in the setting of PD-1 inhibitors, as well as the management. J Drugs Dermatol. 2018;17(7):807-809.

Topics: Adenocarcinoma; Aged; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Azithromycin; Female; Humans; Lung Neoplasms; Melanoma; Programmed Cell Death 1 Receptor; Severity of Illness Index; Stomatitis

Macrolides with 14- and 15-membered ring are characterized by high and extensive tissue distribution, as well as good cellular accumulation and retention. Since macrolide structures do not fit the Lipinski rule of five, macrolide pharmacokinetic properties cannot be successfully predicted by common models based on data for small molecules. Here we describe the development of the first models for macrolide cellular pharmacokinetics. By comparison of cellular accumulation and retention in six human primary cell cultures of leukocytic and lung origin, as well as in lung carcinoma cell line NCI-H292, this cell line was found to be an adequate representative cell type for modeling macrolide cellular pharmacokinetics. Accumulation and retention in the NCI-H292 cells, as well as various physicochemical properties, were determined for a set of 48 rationally designed basic macrolide compounds. Classification models for predicting macrolide cellular accumulation and retention were developed using relatively easily determined and conceptually simple descriptors: experimentally determined physicochemical parameters ChromlogD and CHI IAM, as well as a calculated number of positively charged atoms (POS). The models were further tested and improved by addition of 37 structurally diverse macrolide molecules.

Topics: Cell Line, Tumor; Chemical Phenomena; Humans; Leukocytes; Lung; Lung Neoplasms; Macrolides; Models, Biological; Primary Cell Culture; Respiratory Mucosa; Structure-Activity Relationship

Topics: Anti-Bacterial Agents; Azithromycin; Cell Line; Clarithromycin; Humans; Immunologic Factors; Lung Neoplasms; Tumor Cells, Cultured