Search

Background and Aim: As one of the second-generation epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors, afatinib brings survival benefits to patients with common and rare EGFR mutations. This study aimed to compare the effectiveness and safety of 30 and 40 mg of afatinib in patients with non–small cell lung cancer (NSCLC) using qualitative and quantitative analysis methods so as to provide reference for clinical medication. Methods: The PubMed, Embase, ClinicalTrials.gov, Cochrane Library, China National Knowledge Infrastructure, and WanFang databases were thoroughly searched from inception to February 26, 2021. Two researchers independently screened the literature, extracted data, and evaluated the quality. RevMan and Stata 15.0 were used for meta-analysis. Results: Twelve cohort studies including 1290 patients for final analysis were selected; of which, 1129 patients were analyzed to measure the effectiveness outcomes and 470 patients were analyzed for safety outcomes. In patients with non-brain metastasis, the progression-free survival of the first- or second-line treatment with reduced-dose afatinib was equivalent to the conventional dose. In terms of safety, the reduced dose could significantly lower the incidence of severe diarrhea and severe rash, but not the total incidence of diarrhea, rash, and all levels of paronychia. Conclusions: The incidence of common serious adverse reactions was significantly lower with 30 mg of afatinib than with 40 mg of afatinib in patients with NSCLC. The effectiveness appeared to be similar to that in patients with non-brain metastasis. This study provides a reference for clinical dose reduction of afatinib. Systematic Review Registration: [PROSPERO], identifier [CRD42021238043] [ABSTRACT FROM AUTHOR]

Advances in novel drugs, therapies, and genetic techniques have revolutionized the diagnosis and treatment of cancers, substantially improving cancer patients' prognosis. Although rare tumors account for a non-negligible number, the practice of precision medicine and development of novel therapies are largely hampered by many obstacles. Their low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and subtyping. Sample exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines, insufficient biomarkers for prognosis/efficacy, and inability to identify potential novel therapies in clinical trials. Herein, by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas, we proposed a definition of rare tumor in China, including 515 tumor types with incidences of less than 2.5/100 000 per year. We also summarized the current diagnosis process, treatment recommendations, and global developmental progress of targeted drugs and immunotherapy agents on the status quo. Lastly, we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by NCCN. With this informative report, we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients., (© 2023. Higher Education Press.)

Copyright of Journal of Chinese Pharmaceutical Sciences is the property of Journal of Chinese Pharmaceutical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Since its eruption in China, novel coronavirus disease (COVID‐19) has been reported in most of the countries and territories (>200) of the world with ∼18 million confirmed cases (as of August 3, 2020). In most of the countries, COVID‐19 upsurge is uncontrolled with a significant mortality rate. Currently, no treatment effective for COVID‐19 is available in the form of vaccines or antiviral drugs and patients are currently treated symptomatically. Although the majority of the patients develop mild symptoms and recover without mechanical ventilation for respiratory management, severe respiratory illness develops in a significant portion of affected patients and may result in death. While the scientific community is working to develop vaccines and drugs against the COVID‐19 pandemic, novel alternative therapies may reduce the mortality rate. Recent use of stem cells for critically ill COVID‐19 patients in a small group of patients in China and subsequent Emergency Use Authorization of stem cells by Food and Drug Administration to Global Institute of Stem Cell Therapy and Research and Athersys has created excitement among the medical community. As a result, several clinical trials have been registered using stem cells for COVID‐19 treatment that aim to use different cell sources, dosage, and importantly diverse targeted patient groups. In this brief review, the possibilities of stem cell use in COVID‐19 patients and relevant challenges in their use have been discussed. [ABSTRACT FROM AUTHOR]

Background: Squamous cell carcinoma is the dominant type of esophageal cancer in China with many patients initially diagnosed at advanced stage. Patient-derived xenografts (PDX) models have been developed to be an important platform for preclinical research. This study aims to establish and characterize PDX models using biopsy tissue from advanced esophageal cancer patients to lay the foundation of preclinical application.Methods: Fresh endoscopic biopsy tissues were harvested from patients with advanced esophageal cancer and implanted subcutaneously into NOD/SCID mice. Then, the PDXs were serially passaged for up to four generations. Transplantation was analyzed and genomic characteristics of xenografts were profiled using next-generation sequencing.Results: Twenty-five PDX models were established (13.3%, 25/188). The latency period was 75.12 ± 19.87 days (50-120 days) for the first passage and it decreased with increasing passaging. Other than tumor stages, no differences were found between transplantations of xenografts and patient characteristics, irrespective of chemotherapy. Histopathological features and chemosensitivity of PDXs were in great accordance with primary patient tumors. Each PDX was assessed for molecular characteristics including copy number variations, somatic mutations, and signaling pathway abnormalities and these were similar to patient results.Conclusions: Our PDX models were established from real time biopsies and molecularly profiled. They might be promising for drug development and individualized therapy. [ABSTRACT FROM AUTHOR]

Background: Epidermal growth factor receptor (EGFR) mutations play essential roles in the treatment of non-small cell lung cancer (NSCLC) patients using EGFR tyrosine kinase inhibitors. Detection of EGFR mutations in blood cell-free DNA (cfDNA) seems promising. However, the mutation status in the plasma/serum is not always consistent with that in the tissues. Objectives: The aims of this study were to compare the mutation statuses in plasma to those in tissues and thus to determine the specific subgroups of NSCLC patients who may be the best candidates for EGFR mutation analyses using blood cfDNA. Methods: A total of 111 pairs of tissue and plasma samples were collected. Mutant-enriched PCR and sequencing analyses were performed to detect EGFR exon 19 deletions and exon 21 L858R mutations. Results: Mutations were discovered in 43.2% (48/111) of the patients. The overall rate of consistency of the EGFR mutation statuses for the 111 paired plasma and tissue samples was 71.2% (79/111). The sensitivity and specificity rates of detecting EGFR mutations in the plasma were 35.6% (16/45) and 95.5% (63/66), respectively. The disease stage and tumor differentiation subgroups showed significantly different detection sensitivities; the sensitivity was 10% in early-stage patients and 56% in advanced-stage patients (p = 0.0014). For patients with poorly differentiated tumors, the sensitivity was 77.8%, which was significantly different from those with highly differentiated (20%; p = 0.0230) and moderately differentiated tumors (19%; p = 0.0042). Conclusion: Blood analyses for EGFR mutations may be effectively used in advanced-stage patients or patients with poorly differentiated tumors. [ABSTRACT FROM AUTHOR]

Protease inhibitor phenotypes and serum alpha-1-antitrypsin levels in patients with COPD: A study from Hong Kong KWOK JSY, LAWTON JWM, YEW WW, CHAU CH, LEE J, WONG PC. Respirology 2004; 9: 265–270 Many studies have suggested that an imbalance of protease activation and inhibition might result in COPD with emphysema. Levels of alpha-1-antitrypsin (α1-AT), the key protease inhibitor, are genetically determined by alleles that present in many phenotypes/subtypes, some of which are associated with deficiency of the protein. We prospectively evaluated the prevalence of the protease inhibitor (Pi) alleles and phenotypes together with the serum α1-AT levels in Chinese patients with COPD. The study population comprised 356 patients with COPD. The male-to-female ratio was 4 : 1 with a mean age of 72.4 years (range 44–93 years). Isoelectric focusing was used for Pi phenotyping/subtyping. The frequencies of Pi alleles and phenotypes were compared with the frequencies in 1085 healthy unrelated Chinese control subjects. The serum α1-AT levels were measured by the Cobas Fara assay. PiZ was not detected. No significant difference in distribution of PiM phenotypes/subtypes between patients with COPD and healthy controls was observed, except for M1M3 and M2M3. There was also a significant difference in the proportion of variant S and F alleles between the disease group and the control population. The low prevalence of deficiency Pi phenotypes/subtypes suggests a lack of contribution of α1-AT deficiency to the pathogenesis of COPD in Chinese patients. The strategy of launching an α1-AT deficiency detection program among COPD patients, based on the recommendation of the World Health Organization, may not be readily applicable in our local setting. [ABSTRACT FROM AUTHOR]

Background: The gefitinib compassionate-use programme has enabled >39,000 patients worldwide to receive gefitinib ('Iressa', ZD1839) treatment. This paper reports the outcome of gefitinib treatment in Chinese patients who enrolled into the 'Iressa' Expanded Access Programme (EAP) at the Peking Union Medical College Hospital. Methods: Thirty-one patients with advanced or metastatic non-small-cell lung cancer (NSCLC) that had progressed after prior systemic chemotherapy were eligible to receive oral gefitinib 250 mg/day as part of the EAP. Treatment was continued until disease progression or unacceptable toxicity occurred. The impact of treatment on disease-related symptoms and quality of life (QoL) was evaluated with the Chinese versions of European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ-C30 and QLQ-LC13). Results: Gefitinib was well tolerated. Adverse events (AEs) were generally mild (grade 1 and 2) and reversible. The most frequent AEs were acneform rash and diarrhoea. Only one patient withdrew from the study due to a drug-related AE. The objective tumour response rate was 35.5% (95% confidence interval [CI]: 18.6-52.3); median progression-free survival was 5.5 months (95% CI, 1.6 to 9.4); median overall survival was 11.5 months (95% CI, 5.6 to 17.3). The QoL response rates for five functioning scales and global QoL varied from 56-88%. The main symptom response rates varied from 44-84%. QoL and symptom response were correlated with objective tumour response. Conclusion: Gefitinib demonstrated safety and efficacy as monotherapy in this series of Chinese patients with advanced NSCLC and was also associated with remarkable symptom relief and improvement in QoL. Although clinical trials are needed to confirm these positive findings, the data suggest that treatment with gefitinib may be beneficial for some Chinese patients who do not respond to chemotherapy and have poor prognosis. [ABSTRACT FROM AUTHOR]