CINV related biomarkers and questionnaires

Purpose We assessed the efficacy of palonosetron (PAL) in comparison to granisetron (GRA) for the treatment of CINV using the self-assessment questionnaires. In addition, we analyzed the serum levels of emetic various biomarkers. Methods We conducted a randomized study of 70 patients naïve to chemotherapy. The primary endpoint was the late phase score on the MAT questionnaire. The plasma concentrations of the biomarkers were measured on days 1 and 3. Results There were no statistical differences in the scores on the questionnaires, but the mean values in response to PAL were higher than those in response to GRA. The value of ghrelin on day 1 was significantly higher for GRA than for PAL. Conclusions For the primary endpoint, the score of the late phase on the MAT questionnaire was not statistically different between the PAL and GRA treatment groups. Further studies are needed to clarify the role of ghrelin for the treatment of CINV

GPS and chemotherapy for elderly NSCLC

Background : Although platinum-combination chemotherapy is widely used to treat advanced non-small cell lung cancer (NSCLC), not all elderly patients benefit from this regimen. In this retrospective study, we aimed to evaluate whether the Glasgow Prognostic Score (GPS), an indicator of systemic inflammation and malnutrition, could predict the tolerability and efficacy of platinum-combination chemotherapy among elderly patients with NSCLC. Methods : The eligibility criteria included patients aged ≥ 70 years with NSCLC treated with first-line platinum-combination chemotherapy at Shimane University Hospital between January 2015 and December 2018. Results : Thirty-two patients with NSCLC (median age, 74 years) were included. The GPS scores were 0–1 for 19 patients and 2 for 13 patients. Four chemotherapy cycles were completed by 57.9% and 30.8% of patients in the GPS 0–1 and GPS 2 groups, respectively. The GPS 0–1 group experienced better outcomes than the GPS 2 group (response rate : 26% vs. 15%, P = 0.67 ; median progression-free survival : 4.1 vs. 2.1 months, P = 0.0026 ; median overall survival : 22.8 vs. 9.6 months, P = 0.0092). Conclusions : Platinum-combination chemotherapy demonstrated promising efficacy among elderly NSCLC patients with a GPS 0–1. Therefore, GPS may be crucial in determining whether treatments recommended for younger patients are suitable for older patients with NSCLC

Frail patients with respiratory failure

Background : Older patients with severe respiratory failure have higher mortality rates and are more likely to experience impairments in activities of daily living (ADL). Methods : We retrospectively reviewed patients (≥ 75 years) who received intubation and artificial ventilation for respiratory failure at Shimane University Hospital between November 2014 and December 2020. We compared the outcomes of frail patients with those of self-sufficient patients. Results : Thirty-two patients were included. ADL ability before respiratory failure was rated self-sufficient in 18 patients (self-sufficient group) and not self-sufficient in 14 patients (frail group). None of the patients in either group underwent advanced care planning prior to the onset of respiratory failure. In the self-sufficient and frail groups, the in-hospital mortality rates were 33% and 50%, and the incidence of bedridden patients at discharge was 6% and 43%, respectively. Most patients in the frail group (93%) died or were bedridden. The median hospitalization cost was JPY 2,984,000 for the self-sufficient group and JPY 3,008,000 for the frail group. Conclusion : The overall prognosis of frail older patients who underwent intubation and artificial ventilation was poor. When providing intensive care to such patients, it is important to carefully consider their suitability for the treatment

Novel prospective umbrella-type lung cancer registry study for clarifying clinical practice patterns: CS-Lung-003 study protocol

Introduction Conventional cancer registries are suitable for simple surveillance of cancer patients, including disease frequency and distribution, demographics, and prognosis; however, the collected data are inadequate to clarify comprehensively diverse clinical questions in daily practice. Methods We constructed an umbrella‐type lung cancer patient registry (CS‐Lung‐003) integrating multiple related prospective observational studies (linked studies) that reflect clinical questions about lung cancer treatment. The primary endpoint of this registry is to clarify daily clinical practice patterns in lung cancer treatment; a key inclusion criterion is pathologically diagnosed lung cancer. Under this registry, indispensable clinical items are detected in advance across all active linked studies and gathered prospectively and systematically to avoid excessive or insufficient data collection. Researchers are to input information mutually, irrespective of the relevance to each researcher's own study. Linked studies under the umbrella of the CS‐Lung‐003 registry will be updated annually with newly raised clinical questions; some linked studies will be newly created, while others will be deleted after the completion of the analysis. Enrollment began in July 2017. Discussion We successfully launched the umbrella‐type CS‐Lung‐003 registry. Under this single registry, researchers collaborate on patient registration and data provision for their own and other studies. Thus, the registry will produce results for multiple domains of study, providing answers to questions about lung cancer treatment raised by other researchers. Through such analysis of each linked study, this registry will contribute to the comprehensive elucidation of actual daily practice patterns in lung cancer treatment. Key points CS‐Lung‐003 registry directly integrates multiple linked studies created under the umbrella of this cancer registry to solve various clinical questions regarding daily practice patterns of lung cancer treatment

Current Therapeutic Strategies and Prospects for EGFR Mutation-Positive Lung Cancer Based on the Mechanisms Underlying Drug Resistance

The discovery of activating mutations in the epidermal growth factor receptor (EGFR) gene and the development of EGFR tyrosine kinase inhibitors (TKIs) have led to a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). EGFR mutation-positive NSCLC is common in East Asia, and approximately 50% of adenocarcinomas harbor EGFR mutations. Undoubtedly, EGFR-TKIs, with their promising efficacy, are the mainstay of primary therapy. However, even if tumor shrinkage is achieved, most patients become resistant to EGFR-TKIs and relapse; hence, EGFR-TKIs do not achieve a radical cure. The problem of the development of resistance to targeted drugs has been a persistent challenge. After the role of EGFR T790M mutation in acquired drug resistance was reported, osimertinib, a third-generation irreversible EGFR-TKI, was designed to overcome the resistance conferred by T790M mutation. In addition, some studies have reported the mechanism of drug resistance caused by mutations other than the T790M mutation and strategies to overcome them. Elucidating the mechanism underlying drug resistance development and combining therapeutic approaches are expected to further improve NSCLC prognosis

Erlotinib-induced acute interstitial lung disease associated with extreme elevation of the plasma concentration in an elderly non-small-cell lung cancer patient

We herein describe a case of drug-induced interstitial lung disease (ILD) following treatment with erlotinib. The plasma trough concentration of erlotinib at the time of the ILD diagnosis was extremely elevated compared with the plasma maximum concentration on day 1. We hypothesized that this phenomenon was associated with the pharmacodynamic interaction with a concomitant drug. The present case indicates that erlotinib-induced ILD was associated with a high plasma concentration of erlotinib. Oncologists should be aware of the possibility of ILD induced by erlotinib, especially for patients with co-morbidities

Immune checkpoint inhibitor (ICI)-induced hepatitis diagnosed by liver biopsy followed by ICI-free chemotherapy leading to therapeutic effect: A case of lung cancer treatment

In recent years, the combination of platinum-based chemotherapy and immune checkpoint inhibitors (ICIs) has become the standard treatment for patients with lung cancer. Hepatitis is one of the common toxicities following ICI/chemotherapy. When drug-induced hepatitis occurs, the suspected drug must be discontinued. Since it may be difficult to determine the exact drug causing the hepatitis, liver biopsy may help identify this. We report the case of a patient diagnosed with immune-related adverse event hepatitis from liver biopsy and clinical course.A 45-year-old man with lung adenocarcinoma (stage IV, cT4N3M1c) negative for driver gene mutation was treated with carboplatin (CBDCA), pemetrexed (PEM), and pembrolizumab. Elevated blood aspartate aminotransferase and alanine aminotransferase levels after chemotherapy indicated hepatitis induced by cytotoxic anticancer agents and ICIs. As autoimmune hepatitis was also suspected, liver biopsy was performed and the findings suggested ICI-induced hepatitis. Pembrolizumab was discontinued and CBDCA/PEM was resumed, following which, the primary lesion shrank. When drug-induced hepatitis is suspected, clinicians should actively perform liver biopsy to confirm the diagnosis, so that appropriate therapeutic regimen can be administered

Immune checkpoint inhibitor (ICI)-induced hepatitis diagnosed by liver biopsy followed by ICI-free chemotherapy leading to therapeutic effect: A case of lung cancer treatment

In recent years, the combination of platinum-based chemotherapy and immune checkpoint inhibitors (ICIs) has become the standard treatment for patients with lung cancer. Hepatitis is one of the common toxicities following ICI/chemotherapy. When drug-induced hepatitis occurs, the suspected drug must be discontinued. Since it may be difficult to determine the exact drug causing the hepatitis, liver biopsy may help identify this. We report the case of a patient diagnosed with immune-related adverse event hepatitis from liver biopsy and clinical course.A 45-year-old man with lung adenocarcinoma (stage IV, cT4N3M1c) negative for driver gene mutation was treated with carboplatin (CBDCA), pemetrexed (PEM), and pembrolizumab. Elevated blood aspartate aminotransferase and alanine aminotransferase levels after chemotherapy indicated hepatitis induced by cytotoxic anticancer agents and ICIs. As autoimmune hepatitis was also suspected, liver biopsy was performed and the findings suggested ICI-induced hepatitis. Pembrolizumab was discontinued and CBDCA/PEM was resumed, following which, the primary lesion shrank. When drug-induced hepatitis is suspected, clinicians should actively perform liver biopsy to confirm the diagnosis, so that appropriate therapeutic regimen can be administered