Cachexia is a multifactorial disease characterized by weight loss via skeletal muscle and adipose tissue loss, an imbalance in metabolic regulation, and reduced food intake. It is caused by factors of catabolism produced by tumors in the systemic circulation as well as physiological factors such as the imbalanced inflammatory activation, proteolysis, autophagy, and lipolysis that may occur with gastric, pancreatic, esophageal, lung cancer, liver, and bowel cancer. Cancer cachexia not only negatively affects the quality of life of patients with cancer but also reduces the effectiveness of anti-cancer chemotherapy and increases its toxicity, leading to increased cancer-related mortality and expenditure of medical resources. Currently, there are no effective medical interventions to completely reverse cachexia and no approved drugs. Adequate nutritional support is the main method of cachexia treatment, while drugs that target the inhibition of catabolism, cell damage, and excessive activation of inflammation are under study. This article reviews recent advances in the diagnosis, staging, and evaluation of cancer cachexia.
The increasing use of immune checkpoint inhibitors in tumors has brought new hope of survival to patients with advanced tumors. However, the immune system activated by immune checkpoint inhibitors, mainly activated T‐cells, can attack normal tissues and organs in the body and lead to a variety of adverse effects. In the lung, these attacks can induce checkpoint inhibitor pneumonitis (CIP). CIP is different from known pulmonary interstitial pneumonitis, and has the potential to be fatal if not treated correctly. In this review, we summarize the characteristics of CIP and provide advice on how to manage this disease.
Background: Anlotinib is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor, fibroblast growth factor receptor, platelet‐derived growth factor receptor, and stem cell factor receptor (c‐Kit). In the phase III ALTER‐0303 trial (Clinical Trial Registry ID: NCT 02388919), anlotinib significantly improved overall survival versus placebo in advanced non‐small cell lung cancer patients who had received at least two previous chemotherapy and epidermal growth factor receptor/anaplastic lymphoma kinase targeted therapy regimens. This study summarized adverse event management in this trial.Methods: Patients were randomized (2:1) to anlotinib or placebo up to progression or intolerable toxicity. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 and managed by investigators. Key strategies for preventing and managing the most common adverse events included patient education, supportive care, and dose modification.Results: Between February 2015 and August 2016, 294 patients received anlotinib. A total of 170 (57.8%) patients received antihypertensive medications for hypertension, 53 (18.0%) patients received levothyroxine for hypothyroidism, 24 (8.2%) patients received fibrates for hypertriglyceridemia, 11 (3.7%) patients took cortisone cream for hand‐foot syndrome, and 38 (12.9%) patients received anti‐diarrheal medications for diarrhea. Dose reduction and drug discontinuation were required in 24 (8.16%) and 31 (10.54%) patients in the anlotinib group, respectively.Conclusion: Anlotinb‐related adverse events could be controlled by patient education, prophylactic measures, early and active intervention, and dose modification.
11 November 2024 in Journal of Cachexia, Sarcopenia and Muscle
Background: Cancer cachexia significantly contributes to morbidity and mortality in patients with non‐small‐cell lung cancer (NSCLC). Inflammatory pathways mediated by interleukin‐6 (IL‐6) play a crucial role in the development of cancer cachexia. This study aimed to investigate the use of tocilizumab in the management of NSCLC with coexisting IL‐6‐elevated cachexia.Methods: In this retrospective study, data were collected from patients with NSCLC and concurrent IL‐6‐elevated cachexia who received either tocilizumab plus antitumour therapy or antitumour therapy alone. The primary endpoints were overall survival (OS) and improved modified Glasgow Prognostic Score (mGPS) at Week 12. The secondary endpoints included changes from baseline over 12 weeks in body weight, albumin, C‐reactive protein (CRP) and mGPS. Qualitative improvements in patient self‐rated appetite and fatigue were reported as exploratory analysis.Results: The study included 49 patients diagnosed with NSCLC and IL‐6‐elevated cachexia, Eastern Cooperative Oncology Group performance status of 2–4. Of these, 26 received tocilizumab in combination with antitumour therapy, and 23 received antitumour therapy alone. The majority of these patients were male (87.8%). Baseline characteristics were almost identical between the two groups. The tocilizumab group demonstrated a significantly longer median OS compared to the control group (15.1 vs. 3.2 months; hazard ratio 0.18, 95% confidence interval 0.08–0.38; p < 0.001). The rate of patients surviving with mGPS improvement at Week 12 was significantly higher in the tocilizumab group than in the control group (risk difference 0.88, 95% confidence interval 0.75–1.00; p < 0.001). Over the 12‐week period, significant improvements were observed in body weight, albumin, CRP and mGPS in the tocilizumab group compared to the control group (body weight: 5.15 ± 0.53 kg vs. −5.69 ± 0.76 kg, p = 0.041; albumin: 5.89 ± 0.70 g/L vs. −2.97 ± 0.71 g/L, p < 0.001; CRP: −91.50 ± 7.15 mg/L vs. 9.47 ± 13.69 mg/L, p < 0.001; mGPS: −1.61 ± 0.15 vs. 0.03 ± 0.08, p < 0.001). The tocilizumab group also displayed significantly higher rates of improvement in appetite and fatigue (both p < 0.001). The incidence of Grade 3 or higher adverse events was 34.6% in the tocilizumab group compared to 78.3% in the control group. Tocilizumab‐related adverse events were observed in three patients (11.5%), including two cases of neutropenia and one case of skin and subcutaneous tissue infection.Conclusion: Tocilizumab demonstrated significant benefits in survival and various clinical parameters, including body weight, albumin, CRP, mGPS and symptom burden in patients with NSCLC and concurrent IL‐6‐elevated cachexia. Given the existing unmet medical need for effective interventions for cancer cachexia, tocilizumab may be considered as a potential treatment option.