Background—Alzheimer’s disease (AD) is a multifactorial, progressive, neurodegenerative disease that is characterized by memory loss, personality changes, and a decline in cognitive function. While the exact cause of AD is still unclear, recent studies point to lifestyle, diet, environmental, and genetic factors as contributors to disease progression. The pharmaceutical approaches developed to date do not alter disease progression. More than two hundred promising drug candidates have failed clinical trials in the past decade, suggesting that the disease and its causes may be highly complex. Medicinal plants and herbal remedies are now gaining more interest as complementary and alternative interventions and are a valuable source for developing drug candidates for AD. Indeed, several scientific studies have described the use of various medicinal plants and their principal phytochemicals for the treatment of AD. This article reviews a subset of herbs for their anti-inflammatory, antioxidant, and cognitive-enhancing effects. Methods—This article systematically reviews recent studies that have investigated the role of neuroprotective herbs and their bioactive compounds for dementia associated with Alzheimer’s disease and pre-Alzheimer’s disease. PubMed Central, Scopus, and Google Scholar databases of articles were collected, and abstracts were reviewed for relevance to the subject matter. Conclusions—Medicinal plants have great potential as part of an overall program in the prevention and treatment of cognitive decline associated with AD. It is hoped that these medicinal plants can be used in drug discovery programs for identifying safe and efficacious small molecules for AD.

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IMPORTANCE Adjuvant drugs are used to reduce the risk of tumor recurrence in patients with cancer who are successfully treated with first-line therapy. The same drugs used in the metastatic or first-line setting are often used in the adjuvant setting, and although the resulting adverse effects may be similar between the 2 settings, tolerability may be different. OBJECTIVETo compare the discontinuation rates of drugs in the adjuvant setting and in the metastatic setting in clinical trials of cancer drugs. DESIGN, SETTING, AND PARTICIPANTSThis cross-sectional study examined clinical trials of cancer drugs with results published in major medical and oncology journals between July 2018 through June 2021. Because adjuvant drugs can be used in a metastatic setting, included trials were conducted in an adjuvant setting. Data were analyzed December 2021.EXPOSURES Drugs used in the adjuvant setting, which were also used in the metastatic setting for the same tumor indication. MAIN OUTCOMES AND MEASURESDiscontinuation rates in the adjuvant and metastatic settings, which were calculated by dividing the total number of study participants who withdrew or discontinued because of adverse events by the number of participants allocated to the drug arm. RESULTSA total of 29 trials with a drug being used in the adjuvant and metastatic setting were found. In the adjuvant setting, the median (IQR) age for study participants was 58.0 (52.0-63.5) years, and the median (IQR) percentage of male participants was 55.5% (0.9%-64.8%). In the metastatic setting, the median (IQR) age for study participants was 61 years, and the median (IQR) percentage of male participants was 55.2% (2.0%-66.0%). Overall, a median (IQR) 21.4% (17.7%-29.4%) of participants discontinued because of adverse events or patient withdrawal in the adjuvant setting compared with a median (IQR) 15.9% (9.7%-21.3%) in the metastatic setting (P = .01). Checkpoint inhibitors (median [IQR] rate of discontinuation, 21.4% [18.6%-31.3%] vs 15.2% [9.9%-19.5%]; P = .01) and targeted drugs (median [IQR] rate of discontinuation, 27.7% vs 14.0%; P < .001) demonstrated a higher rate of discontinuation in the adjuvant setting while cytotoxic drugs (median [IQR] rate of discontinuation, 16.6% [12.2%-23.3%] vs 25.5% [19.8%-28.8%]; P = .07) showed no difference between the 2 settings. The largest differences between adjuvant and metastatic discontinuation rates were for sorafenib (renal cell carcinoma, 43.8% vs 5.5%; difference, 38.2%), imatinib (gastrointestinal stromal tumor, 37.4% vs 6.1%; difference, 31.2%), and erlotinib (non-small cell lung cancer, 37.5% vs 8.4%; difference, 29.0%). CONCLUSIONS AND RELEVANCEIn this cross-sectional study of clinical trials that involved novel cancer drugs, drugs used in the adjuvant setting were associated with significantly higher (continued) Key Points Question How does the percentage of patients who withdraw from adjuvant trials because of adverse events compare with patients who withdraw from metastatic trials for the same drug? Findings In this c...

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