Treatment-related Adverse Effects Research Articles

Cenobamate for treatment-resistant focal seizures: current evidence and place in therapy.

BackgroundCenobamate is newly approved for partial-onset seizures in adults, albeit the mechanism of its action remain poorly understood.Methods This article aims to review the efficacy, safety, and tolerability of cenobamate in treating partial-onset seizures.Data Collection:The English language articles were searched in the National Institute of Health clinical trials registry, PubMed, and the Cochrane library between 2010 and June 2021 using the keywords cenobamate, YKP 3089, and seizure, and filter “trial” was applied. Results:A total of 31 articles were retrieved. Eventually, two randomized, double-blind, multicenter clinical trials involving 659 patients were analyzed. Cenobamate has shown significant reduction in seizure frequency compared to placebo. In cenobamate group, a greater number of participants showed ≥50% reduction in seizure frequency, adverse effects, and drug discontinuation compared to placebo. Multiple drug-drug interactions with other anti-seizure drugs were also observed.ConclusionsBased on the findings of these trials, cenobamate seems to be an attractive option for treatment-resistant partial-onset seizures; however, multiple treatment-related adverse effects and drug-drug interactions are the areas of concern.

Nisin ZP, an Antimicrobial Peptide, Induces Cell Death and Inhibits Non-Small Cell Lung Cancer (NSCLC) Progressionin vitro in 2D and 3D Cell Culture.

Lung cancer is the leading cause of cancer deaths globally with most of the reported cases (> 85%) associated with non-small cell lung cancer (NSCLC). Current therapies have enhanced the overall survival rate of patients but treatment-related adverse effects and increase in drug-resistance limit the success of these treatment options. Antimicrobial peptides (AMPs) have gained interest as anticancer agents as they selectively target cancer cells and decrease the possibility of resistance. Nisin ZP is a polycyclic antimicrobial peptide produced by the Gram-positive bacterium, Lactococcus lactis and is commonly used as a food preservative. Nisin ZP has recently demonstrated anticancer activity in melanoma, head and neck squamous cell carcinoma, hepatic, colon, and blood cancer. In this study, we evaluated the anticancer potential of nisin ZP and assessed the underlying mechanisms in NSCLC cells. The results revealed that nisin ZP induced selective toxicity in cancer (A549 and H1299) cells compared to healthy (HEK293) cells after 48h of treatment. Nisin ZP exposure induced apoptosis and cell cycle arrest (G0/G1 phase) in NSCLC cells irrespective of tumor protein p53 expression. The cancer cell proliferation was inhibited via non-membranolytic pathways by mitochondrial membrane depolarization and elevation in reactive oxygen species (ROS) generation. Furthermore, nisin ZP decreased cancer cells' clonal expansion and migration, demonstrating potential use against highly metastatic NSCLC. The 3D spheroid growth and cell viability of the A549 cells were significantly inhibited by nisin ZP compared to control. Overall, the results suggest an excellent antitumor potential in vitro and, thus, can further be developed as a novel therapeutic for NSCLC.

Preclinical characterization of the novel anti-SIRPα antibody BR105 that targets the myeloid immune checkpoint

BackgroundThe CD47-SIRPα pathway acts as an important myeloid cell immune checkpoint and targeting the CD47/SIRPα axis represents a promising strategy to promote antitumor immunity. Several CD47-targeting agents show encouraging early...

Investigational New Drug Enabling Nonclinical Safety Pharmacology Assessment of the Iminosugar UV-4, a Broad-Spectrum Host-Targeted Antiviral Agent.

UV-4 (N-(9-methoxynonyl)-1-deoxynojirimycin) is a broad-spectrum antiviral drug candidate with demonstrated activity in vitro and in vivo against multiple, diverse viruses. Nonclinical safety pharmacology studies were conducted to support the filing of an Investigational New Drug (IND) application. Preliminary in vitro pharmacology testing evaluating potential for binding to "off-target" receptors and enzymes indicated no significant liability for advanced development of UV-4. The safety pharmacology of UV-4 was evaluated in the in vitro human ether-à-go-go-related gene (hERG) assay, in a central nervous system (CNS) study in the mouse (modified Irwin test), in a respiratory safety study in conscious mice using whole body plethysmography, and in a cardiovascular safety study in conscious, radiotelemetry-instrumented beagle dogs. There were no observed adverse treatment-related effects following administration of UV-4 as the hydrochloride salt in the hERG potassium channel assay, on respiratory function, in the CNS study, or in the cardiovascular assessment. Treatment-related cardiovascular effect of decreased arterial pulse pressure after 50 or 200mg of UV-4/kg was the only change outside the normal range, and all hemodynamic parameters returned to control levels by the end of the telemetry recording period. These nonclinical safety pharmacology assessments support the evaluation of this host-targeted broad-spectrum antiviral drug candidate in clinical studies.

Evaluation of cytogenetic and molecular markers with MTX-mediated toxicity in pediatric acute lymphoblastic leukemia patients.

Pediatric acute lymphoblastic leukemia (pALL) patients have better overall survival and methotrexate (MTX) is an effective drug used in their treatment. However, the treatment-related adverse effects (TRAEs) have a bigger impact on the therapy. In this study, we have evaluated the association of polymorphisms in genes encoding proteins engaged in MTX metabolism, and the cytogenetic aberrations with TRAEs. A total of 115 patients between the age of 1 and 18years (average: 6.6) under maintenance therapy were selected for the study. SLC19A1 (c.80G > A), MTHFR (c.677C > T; c.1298A > C), and TYMS (c.*450_*455del) genotypes were determined using PCR techniques and Sanger sequencing. Cytogenetic and SNP findings were analyzed for any association with the reported toxicities using odds ratio, chi-square test, multifactor dimensionality reduction (MDR) analysis for synergistic effect and, multinomial logistic regression analysis for the likelihood of adverse events. Among the evaluated genetic variations, SLC19A1 (c.80G > A) was significantly associated with TRAEs (OR = 5.71, p = 0.002). Multinomial logistic regression analysis (chi-sq = 16.64, p < 0.001) and MDR analysis (chi-sq = 10.51 p < 0.001) confirmed the finding. On the other hand, no significant association was observed between adverse events and any specific cytogenetic aberration. SLC19A1 facilitates the import of cyclic dinucleotides and reduced folates, evaluating genotypes in this gene can help in better management of patients on methotrexate treatment. Assessing a broader gene panel can help in finding more associated markers and delivering personalized medicine to the patients.

Topical dapsone in the treatment of acne: a systematic review.

Acne is one of the most common dermatological disorders. Initial therapies for acne include topical retinoids, benzoyl peroxide, and topical clindamycin. However, patients who fail initial therapies may benefit from alternative topicals, including dapsone gel. To analyze the current literature studying the efficacy of topical dapsone in the treatment of acne. PubMed, Embase, and Cochrane Library were systematically searched for clinical trials examining the efficacy of topical dapsone in the treatment of acne. Fourteen studies were included in the analysis. Dapsone monotherapy showed a treatment success rate of 40.1-69.4% for dapsone gel 5% and 29.8-47.0% for dapsone gel 7.5% when used for 12-16 weeks. In all studies, inflammatory lesions decreased by a larger percentage than noninflammatory or total lesions. Dapsone gel was also studied in combination with various other acne treatments, including doxycycline, oral isotretinoin, benzoyl peroxide, and topical retinoids. While mild treatment-related adverse effects, most commonly consisting of skin irritation, occurred in 2.0-75.0% of participants, no major treatment-related adverse effects were reported. Limitations of the study include variable treatment regimens making it difficult to compare results across studies. Additionally, adverse effects and skin irritation were reported differently, and potential selection biases exist in the randomized trials. Dapsone gel offers a safe and promising alternative therapy for patients with difficult to treat acne or those who experience adverse effects to first-line therapies.

Subchronic toxicological evaluation of EnXtra™ (standardised extract of Alpinia galanga rhizome) in rats.

Alpinia galanga is a commonly used ingredient in Asian food and traditional medicine. But an extract of the rhizome had never been used commercially in food supplements and functional foods. There is some evidence of safety and tolerability in humans for a proprietary A.galanga rhizome extract (EnXtra™) and it is Generally Recognised as Safe (GRAS) in the US already. However, this botanical ingredient has not been evaluated for its subchronic toxicity in rats to confirm its safety in wider food applications. Sprague Dawley rats were orally administered the test item for 90days by following OECD (Test Guideline: 408), with a recovery period of 28days. Cumulative effects and No Observed Adverse Effect Level (NOAEL) were estimated. EnXtra™ was administered orally at 0, 1,000, 2,000 and 3,000mgkg-1 body weight (b. wt.) with additional vehicle and high dose recovery groups. Observations included clinical signs, haematology, clinical chemistry, gross pathology and histopathology. On terminal sacrifice, no treatment-related adverse effects were observed viz., clinical signs, mortality, body weight changes and feed consumption parameters. Haematology, clinical biochemistry and thyroid hormone levels were within the normal range. Further, no treatment-related gross and microscopic pathological lesions were observed across the treatment groups. Based on the results of the toxicological evaluation, NOAEL of A.galanga rhizome extract (AGRE) was fixed at 3,000mgkg-1b. wt. per day and ADI of 1800mg day-1 in the case of humans.

The management of sexual problems in cancer patients

. The management of sexual problems in cancer patients. Sexual dysfunction is one of the most common and distressing consequences of cancer treatment. Many survivors face long-term effects such as treatment-induced menopause, altered gonadal function, and significant surgical disfigurement but some treatment-related sexual adverse effects are short-term. Many survivors do not feel prepared for potential sexual changes and often do not receive adequate support to manage sexual dysfunction. A concise review of the most common sexual problems experienced by cancer ptients is presented together with the main evidence based interventions to suggest to address sexual dysfunction.

Long-term satisfaction with curative treatment and follow-up in prostate cancer survivors

Purpose In a cross-sectional observational study to explore long-term satisfaction with treatment among men who had undergone radical prostatectomy (RP) or definitive pelvic radiotherapy (RT) for prostate cancer (PCa). Methods After mean 7 years from therapy (range: 6–8), 431 PCa-survivors (RP: n = 313, RT: n = 118) completed a mailed questionnaire assessing persistent treatment-related adverse effects (AEs) (Expanded Prostate cancer Index Composite [EPIC-26]) and seven Quality indicators describing satisfaction with the health care service following a most often general practitioner (GP)-led follow-up plan. A logistic regression model evaluated the associations between long-term satisfaction and treatment modality, age, the seven satisfaction-related Quality indicators, and persistent AEs. The significance level was set at p< .05. Results Four of five (81%) PCa-survivors reported long-term satisfaction with their treatment. In a multivariable model, satisfaction was positively associated with sufficient information about treatment and AEs, patient-perceived sufficient cooperation between the hospital and the GP and sufficient follow-up of AEs (ref.: insufficient). Age ≥70 years (ref.: <70) and a rising summary score within the EPIC-26 sexual domain additionally increased long-term satisfaction. The treatment modality itself (RP versus RT) did not significantly impact on satisfaction. Conclusions The majority of curatively treated PCa-survivors are satisfied with their treatment more than 5 years after primary therapy. Sufficient information, improved cooperation between the hospital specialists and the responsible GP and optimized follow-up of AEs may further increase long-term satisfaction among prostatectomized and irradiated PCa-survivors.

Real Life Experience with Individualized Doses of Incobotulinumtoxina in Patients with Severe Spasticity Due to Acquired Brain Injury

The objective of the present study was to evaluate the effectiveness and tolerability of incobotulinumtoxinA, at doses according to individual needs, in 10 patients with acquired brain injury and severe upper and lower limb spasticity. Patients received a multipattern periodic treatment with ultrasound-guided injections of incobotulinumtoxinA at doses of 800-900 U in the upper and lower limbs. The mean number of injection cycles per patient was 4.2. The 0-10 visual analogue scale for pain score decreased significantly from pre-injection (mean: 4.7) to four-week post-injection (mean: 0.7). Similarly, the mean Ashworth Scale score (muscular tone assessment) at four-week post-injection (mean: 1.4) was significantly lower than at injection (mean: 2.5). Except for two patients in one pattern, all cases showed an improvement in passive range of motion assessments using goniometry. All patients reported maximum satisfaction with the treatment, all reporting “much improved” after the treatment. No treatment-related adverse effects were observed during the study. Individualized doses of incobotulinumtoxinA are effective and well-tolerated for this type of patients and allow better management of their severe spasticity. Therefore, individualization of doses should be taken into account for optimizing clinical outcomes and improving the patients’ treatment satisfaction.

Early versus standard initiation of terlipressin for HRS-AKI in ACLF patients- a randomized controlled trial (ETERLI).

Background and Aim: Terlipressin infusion has been shown to be effective in treatment of HRS-AKI. Progression of AKI is rapid in ACLF patients. Response to terlipressin correlates with stage of AKI and ACLF. Aims: We investigated whether early initiation of therapy might improve response to terlipressin in HRS-AKI patients by day 7. Methods: Consecutive ACLF patients with stage II/III AKI despite albumin resuscitation(40g) for 12 hours were randomized to receive early terlipressin at 2mg/24 hour plus albumin (ET, n=35) or standard therapy (ST, n=35), albumin alone for 48h followed by terlipressin. The primary end-point was AKI reversal by day 7. The main secondary end-points included need for dialysis, treatment-related adverse effects and mortality at day 28 and Day 90. Results: Baseline parameters including AKI stage and ACLF AARC scores in two groups were comparable. Full AKI response at day 7 was observed in 24/35 (68.6%) patients in ET group compared to 14/35(40 %) in ST group [P-0.03]. There was significant improvement in ACLF grades from baseline to Day 7 in ET group (ACLF grade II to I in 16 patients). Five patients in each group developed progressive AKI requiring dialysis. Significantly more patients died in ST group (23/35; 65.7 %) within 28 days compared to 14/35 (40 %) in ET group [P-0.031]. The 90-day mortality in ST group was higher (69.6% vs. 57.2%; P-0.071). Baseline MELD score [HR: 0.987 (95% CI: 0.864-3.211); P-0.02], HE at presentation [HR: 4.405 (95% CI: 1.776-10.927); P-0.001] and admission BUN [HR: 1.007 (95% CI: 1.000-1.013); P-0.036] were independent predictors of 28-day mortality. Overall, 9 patients had terlipressin related adverse effects, none was life threatening. Conclusion: In patients with ACLF, early initiation of terlipressin for AKI persisting despite 12 hours of volume expansion with albumin helps in early reversal of AKI and regression of ACLF stage with significantly short-term mortality benefit.

Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for resectable esophageal squamous cell carcinoma

BackgroundProgrammed cell death 1 (PD-1) blockade induces tumor regression in patients with advanced esophageal squamous cell carcinoma (ESCC); however, little is known about the efficacy of PD-1 blockade as neoadjuvant...

Subchronic toxicity and genotoxicity studies of Hericium erinaceus β-glucan extract preparation

The medicinal effects of Hericium erinaceus have been long documented in scientific studies of Eastern traditional medicine. It is widely consumed, because of its nutritional qualities and perceived health benefits. Also, it is rich in β-glucans, which has been shown to have immunomodulating and antitumor effects. The objective of the present study was to investigate adverse effects, if any, of β-glucan extract preparation from H. erinaceus in subchronic toxicity and genotoxicity studies. The conduct of these studies was in compliance with Good Laboratory Practice (GLP) and test guidelines established by the Organization for Economic Cooperation and Development (OECD). In the subchronic toxicity study, Sprague Dawley rats (12/sex/group) were administered (gavage) H. erinaceus β-glucan extract preparation at dose levels of 0, 500, 1000 and 2000 mg/kg body weight (bw)/day for 90 days. Treatment with H. erinaceus β-glucan extract preparation did not result in any toxicologically significant treatment-related changes in clinical observations, ophthalmic examinations, body weights, body weight gains, feed consumption, and organ weights. Clinical pathology including hematology, serum chemistry, urinalysisand terminal necropsy (gross or histopathology findings) did not reveal any treatment-related adverse effects. The results of genotoxicity studies as evaluated by gene mutations in Salmonella typhimurium, in vitro chromosome aberrations and in vivo micronucleus test in mice did not reveal any genotoxicity of H. erinaceus β-glucan extract preparation. Based on the subchronic study, the no observed-adverse-effect level (NOAEL) for H. erinaceus β-glucan extract preparation was determined as 2000 mg/kg bw/day, the highest dose tested.

Obesity and prostate cancer: A narrative review

Overweight and obese men with prostate cancer are at an increased risk of disease recurrence, exacerbated treatment-related adverse effects, development of obesity-related comorbidities, earlier progression and development of metastatic disease, and higher all-cause and prostate cancer-specific mortality. The physiological mechanisms associating obesity with poor prostate cancer outcomes remain largely unknown; however, an increased inflammatory environment and metabolic irregularities associated with excess fat mass are commonly postulated. Although research is limited, fat loss strategies using exercise and nutrition programmes may slow down prostate cancer progression and improve a patient's prognosis. This review is an overview of: 1) the association between obesity and poor prostate cancer prognosis; 2) potential physiological mechanisms linking obesity and prostate cancer progression; 3) the effect of obesity on treatments for prostate cancer; and 4) the potential for weight loss strategies to improve outcomes in patients with prostate cancer.

Atogepant for the prevention of episodic migraine in adults.

Objective:Atogepant is a newly approved medication for the prevention of migraine. This review aims to discuss the efficacy, safety, cost, and place in therapy of atogepant.Methods:The authors performed a systematic search for sources, including articles, abstracts, and poster presentations. Queried databases were the National Institute of Health, US National Library of Medicine Clinical Trials, PubMed, European PMC, and the Cochrane Library. Search terms included atogepant, QULIPTA™, AGN-241689, MK-803, and N02CD07. Full-text, English language, randomized-controlled trials from 1 February 2012 to 1 February 2022 were included in the review. Additional relevant prescribing information, abstracts, and articles identified through the search were considered for inclusion in this review. A total of 193 database entries were evaluated for inclusion in this narrative review. Three articles representing two randomized controlled trials were reviewed.Results and conclusions:Atogepant, a small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist, is a daily oral treatment for migraine prevention. In placebo-controlled clinical trials, atogepant decreased mean monthly migraine days (MMD) over 12 weeks in patients with episodic migraine. Major treatment-related adverse effects include nausea and constipation. Long-term placebo-controlled efficacy and safety studies, chronic migraine studies, and studies in patients that failed more than two classes of preventive therapies are still pending. Atogepant represents one of many novel therapies for the prevention of migraine. To date, no head-to-head comparisons of atogepant versus other agents indicated for migraine prevention have been published. Atogepant offers patients an alternative therapy to injectable or infusion monoclonal antibody treatments and offers an alternative to non-specific migraine medications that are associated with poor tolerability. Due to its high cost and narrower therapeutic indications, atogepant may be reserved for a small subset of migraineurs who prefer oral therapy.

Efficacy and Safety of Epirubicin Combined with Temozolomide for Treatment of Advanced Leiomyosarcoma.

BackgroundLeiomyosarcoma (LMS) accounts for 24% of all soft tissue sarcomas (STSs) and this STS subtype has high metastatic potential. Previous studies indicated the best median progression-free survival (mPFS) time was 9.2 months and the best overall response rate (ORR) was 30.9%. We evaluated the efficacy and safety of epirubicin combined with temozolomide (EPI-TMZ) for treatment of advanced LMS.MethodsThis was a retrospective review of the records of patients with advanced LMS at the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. All patients initiated EPI-TMZ treatment between January 2018 and December 2020.ResultsWe examined 15 patients who received EPI-TMZ for LMS. This was a first-line treatment in 6 patients, a second- or third-line treatment in 7 patients, and a fourth-line treatment in 2 patients. At the time of data cutoff (April 25, 2021), the median PFS was 10 months, 1 patient had clinical complete response (cCR), 7 had partial response (PR), and 7 had stable disease (SD). The overall response rate (ORR) was 53.3% (8/15) and the disease control rate (DCR) was 100.0% (15/15). The most common treatment-related adverse effects were leukopenia, neutropenia, thrombocytopenia, anemia, nausea, vomiting, fatigue, and oral mucositis. One patient had severe adverse effect (febrile neutropenia), but there were no treatment-related deaths.ConclusionEPI-TMZ is potentially effective for treatment of advanced LMS, and the adverse effects appear tolerable. EPI-TMZ provided better outcomes than reported in previous studies of other treatments for advanced LMS.

Effects of transgenic Bacillus Thuringiensis maize (2A-7) on the growth and development in rats

This study aimed to determine the effects of genetically modified insect-resistant maize (2A-7) on the growth and development in developing rats. Rats were fed a diet formulated with 2A–7 maize and were compared with rats fed a diet formulated with non-transgenic maize (CK group) and rats fed AIN-93G diet (BC group). 2A-7 maize was formulated into diets at ratios of 82.4% (H group) and 20.6% (L group); non-transgenic maize was formulated into diets at a ratio of 82.4%. From the first day of pregnancy, adult rats were divided into four groups and fed with the above four diets, respectively. Weaning on postnatal day 21, the diets of offspring were consistent with their parents. The results showed that body weight, hematology, serum biochemistry, organ weight, organ coefficients and allergenicity of offspring fed with 2A–7 maize were comparable with those in the CK and BC groups. In physiological and behavioral development experiments, there was no statistically significant difference among groups. Although mCry1Ab proteins were detected in organs and serum, no histopathological changes were observed among groups. In conclusion, A-7 maize cause no treatment-related adverse effects on offspring, indicating that 2A-7 maize is safe for developing rats.

Efficacy of Penile Low-Intensity Shockwave Therapy and Determinants of Treatment Response in Taiwanese Patients with Erectile Dysfunction.

Background: Erectile dysfunction (ED) remains an emotional wrench to patients and a therapeutic challenge to urologists in andrology clinics worldwide. This is, in part, related to refraction to, or transient effect of phosphodiesterase 5 inhibitors (PDE5i), coupled with patients’ dissatisfaction with this treatment modality. Low-intensity extracorporeal shockwave therapy (Li-ESWT) is an evolving treatment option, with promising curative potential. Current international guidelines are inconclusive, bear weak recommendation strength, and lack ethnogeographic consensus. Objectives: This study evaluated the safety, efficacy, and effect duration of Li-ESWT, as well as exploring disease-associated determinants of treatment success in Taiwanese males with ED. Methods: A cohort of 69 eligible cases treated with 12 sessions of Li-ESWT and followed up for at least 12 months after treatment, between January 2018 and December 2019 at our medical facility, was used. The present single-center, retrospective, non-randomized, single-arm study employed standardized erectile function evaluation indices, namely, the five-item International Index of Erectile Function (IIEF-5) and Erection Hardness Score (EHS). Clinicopathological analyses of selected variables and comparative analyses of time-phased changes in the EF indices relative to baseline values were performed. Evaluation of treatment success was based on minimal clinically important difference (MCID), using a binomial logistic regression model. Results: The median age and duration of ED for our Taiwanese cohort were 55 years and 12 months, respectively, and an average of 31.3% presented with co-morbidities. The mean improvement in IIEF-5, EHS, and quality of life (QoL) domain scores relative to the baseline values was statistically very significant (p < 0.001) at all indicated follow-up time-points. When stratified, Taiwanese patients with severe and moderate ED benefited more from Li-ESWT, compared with those in the mild or mild-to-moderate group. Patients’ pre-Li-ESWT PDE5i response status was not found to significantly influence Li-ESWT response. Univariate analysis showed that age > 45 years (p = 0.04), uncontrolled diabetes mellitus (p = 0.04), and uncontrolled hyperlipidemia (p = 0.01) were strongly associated with Li-ESWT efficacy; however, only age > 45 years (p = 0.04) and uncontrolled hyperlipidemia (p = 0.03) were found to be independent negative predictors of Li-ESWT success by the multivariate logistic model. Follow-up was uneventful, with no treatment-related adverse events or side effects reported. Of the treated patients, 86.1% indicated satisfaction with the treatment regimen, and over 90% indicated they would recommend the same therapy to others. Conclusions: Li-ESWT is a safe and efficacious therapeutic modality for Taiwanese patients with ED. Uncontrolled hyperlipidemia and age > 45 years are independent negative predictors of treatment success for this cohort.

Integrative oncology: Addressing the global challenges of cancer prevention and treatment.

The increase in cancer incidence and mortality is challenging current cancer care delivery globally, disproportionally affecting low- and middle-income countries (LMICs) when it comes to receiving evidence-based cancer prevention, treatment, and palliative and survivorship care. Patients in LMICs often rely on traditional, complementary, and integrative medicine (TCIM) that is more familiar, less costly, and widely available. However, spheres of influence and tensions between conventional medicine and TCIM can further disrupt efforts in evidence-based cancer care. Integrative oncology provides a framework to research and integrate safe, effective TCIM alongside conventional cancer treatment and can help bridge health care gaps in delivering evidence-informed, patient-centered care. This growing field uses lifestyle modifications, mind and body therapies (eg, acupuncture, massage, meditation, and yoga), and natural products to improve symptom management and quality of life among patients with cancer. On the basis of this review of the global challenges of cancer control and the current status of integrative oncology, the authors recommend: 1) educating and integrating TCIM providers into the cancer control workforce to promote risk reduction and culturally salient healthy life styles; 2) developing and testing TCIM interventions to address cancer symptoms or treatment-related adverse effects (eg, pain, insomnia, fatigue); and 3) disseminating and implementing evidence-based TCIM interventions as part of comprehensive palliative and survivorship care so patients from all cultures can live with or beyond cancer with respect, dignity, and vitality. With conventional medicine and TCIM united under a cohesive framework, integrative oncology may provide citizens of the world with access to safe, effective, evidence-informed, and culturally sensitive cancer care.

Real-world efficacy and safety of anlotinib as third- or further-line treatment in refractory small cell lung cancer.

As a novel antiangiogenic multi-target tyrosine kinase inhibitor recently approved in China, anlotinib has exhibited promising anticancer efficacy and acceptable safety profile in the salvage treatment of small cell lung cancer (SCLC) in clinical trials. Here we retrospectively investigated the efficacy and safety of anlotinib as third- or further-line treatment in patients with refractory SCLC. A total of 40 patients with refractory SCLC treated with anlotinib monotherapy were included in this study. The clinicopathological data, treatment information, survival data and safety data were retrospectively collected. Survival curves were constructed using the Kaplan-Meier method. Univariate analysis was performed by log-rank testing. Altogether, 40 patients of extensive-stage SCLC or progressive limited-stage SCLC received anlotinib monotherapy as third- or further-line treatment from July 2018 to June 2020. Four patients achieved partial response (PR), 14 patients achieved stable disease (SD), no complete response (CR) was recorded, and 22 patients experienced progressive disease (PD). The disease control rate (DCR) was 45.0%. The median progression-free survival (PFS) was 3.0months (95% CI 2.241-3.759), and the median overall survival (OS) was 7.8months (95% CI 3.190-12.410). The common adverse effects (AEs) included hypertension, fatigue, anorexia, cough, rash and nausea. Grade 3 treatment-related AEs occurred in 3 (7.5%) patients. One patient interrupted anlotinib treatment due to repeated grade 1 epistaxis. Univariate analysis revealed that patients without liver metastases, previously treated with radiotherapy or with Eastern Cooperative Oncology Group (ECOG) scores of 0 or 1 had longer OS with anlotinib treatment. Cox regression analysis demonstrated that patients without liver metastases and patients with ECOG score ≤ 1 had longer PFS, while patients without liver metastases had longer OS. Anlotinib is beneficial to refractory SCLC as third- or further-line treatment, especially in patients without liver metastasis and with better physical status. Related adverse effects are tolerable and manageable.