Med J Aust. 2021 Oct 8. doi: 10.5694/mja2.51299. Online ahead of print.

NO ABSTRACT

PMID:34622959 | DOI:10.5694/mja2.51299

Rheumatol Int. 2021 Oct 7. doi: 10.1007/s00296-021-05017-9. Online ahead of print.

ABSTRACT

Data regarding COVID-19 vaccine efficacy and adverse events (AE) in patients with autoimmune and inflammatory rheumatic diseases (AIIRD) have been published recently although these mostly include the mRNA vaccines (Pfizer-BioNTech and Moderna) and the ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca). This research aimed to study the prevalence of AE presented with six different SARS-CoV-2 vaccines {ChadOX1 nCoV-19 (AZD1222), Ad5-nCoV2, Ad26.COV2.S, mRNA-1273, BNT162b2, and CoronaVac} in Mexican patients with AIIRD. We performed a cross-sectional study about vaccine history. Two hundred and twenty five consecutive patients were recruited, mean age was 50.7 years and the majority (n = 213; 94.6%) were females. One hundred and seven (47.5%) received BNT162b2 mRNA, 34 (15.1%) Ad5-nCoV, 29 (12.8%) mRNA-1273, 28 (12.4%) ChAdOX1 nCoV-19 (AZD1222), 22 (9.7%) CoronaVac and 5 (2.2%) Ad26.COV2.S. The vaccines that had the most AE proportionally to the number of patients vaccinated were Janssen (5; 100%) followed by Pfizer-BioNTEch (86; 80%) and CanSinoBIO (27; 79.4%). Localized pain was the most frequent (158; 70.2%) AE. Fatigue (78; 34.7%), headache (69; 30.6%) and muscle ache (66; 29.3%) were the most common systemic symptoms. No serious AE that required medical attention or hospitalization were reported. The current results support the safety of different COVID-19 vaccines in patients with AIIRD. This information can help fight vaccine hesitancy in this population.

PMID:34622311 | DOI:10.1007/s00296-021-05017-9

Thorac Cancer. 2021 Oct 6. doi: 10.1111/1759-7714.14185. Online ahead of print.

ABSTRACT

Immune checkpoint inhibitors can often trigger immune-related adverse events (irAEs), such as relapse of pre-existing interstitial pneumonia. Here, we report the case of an 88-year-Japanese man diagnosed with advanced lung adenocarcinoma with a high tumor proportion score of programmed death-ligand 1. Six years earlier, he had developed organizing pneumonia (OP), a subtype of interstitial pneumonia, that was treated with steroid pulse therapy maintained with prolonged prednisolone administration. We initiated pembrolizumab as the first-line treatment. One month after the first pembrolizumab administration, high resolution computed tomography (HRCT) of the chest demonstrated ground-glass opacities and consolidations. We suspected pembrolizumab-induced OP relapse, an irAE. His oxygenation was normal; therefore, we discontinued pembrolizumab without additional treatment for OP relapse. Four months after OP relapse, HRCT showed no new findings. After significant amelioration of OP, although the size of the tumor shadow remained the same on HRCT, positron emission tomography-computed tomography demonstrated the disappearance of the standardized uptake value of the primary tumor, mediastinal lymph nodes, and pleural nodules. In conclusion, this is the first report of a dramatic, significant metabolic response after a single pembrolizumab treatment despite the relapse of pre-existing OP in a patient with advanced lung adenocarcinoma.

PMID:34617405 | DOI:10.1111/1759-7714.14185

SAGE Open Med Case Rep. 2021 Sep 30;9:2050313X211050465. doi: 10.1177/2050313X211050465. eCollection 2021.

ABSTRACT

Angioedema is a serious adverse event that can manifest as lower extremity edema, face swelling, rash, hives, and a swollen tongue, which can sometimes lead to airway constriction and death. It is a well-documented reaction within the angiotensin-converting enzyme inhibitor drug class, where the bradykinin pathway leads to angioedema. We report a case where a patient experienced angioedema after taking venlafaxine. We evaluated other antidepressants as potential treatment options for the patient. We further examined potential cross-reactivity between antidepressants in order to find alternative medications for patients that experience serious adverse effects.

PMID:34616557 | PMC:PMC8488410 | DOI:10.1177/2050313X211050465

Acta Med Indones. 2021 Jul;53(3):326-330.

ABSTRACT

SARS CoV-2 virus has infected more than 200 million people worldwide and more than 4.4 million in Indonesia. The vaccination program has become one of the solutions launched by many countries globally, including Indonesia, to reduce the transmission rate of COVID-19. Various vaccination platforms are produced, such as inactivated, viral vector, mRNA, and protein subunit. The vaccination booster program with mRNA platform (Moderna) was launched by the Indonesian government to give better protection for health care workers, particularly from delta variant. In this case report, we discuss one of the typical side effects of Moderna vaccine, which is referred to as the COVID arm.

PMID:34611073

Invest New Drugs. 2021 Oct 6. doi: 10.1007/s10637-021-01180-9. Online ahead of print.

ABSTRACT

Background Dysregulation of histone deacetylases (HDACs) is common in cancer and is critical to the development and progression of the majority of tumors. This first-in-human Phase Ia study assessed the safety, efficacy, and pharmacokinetics (PK) of OBP-801, a cyclic depsipeptide class I HDAC inhibitor. Methods Adult patients with advanced solid tumors were treated in 3 dose cohorts (1.0 mg/m2, 2.0 mg/m2 or 2.8 mg/m2) of OBP-801 that was administered via intravenous infusion weekly. Initially, an accelerated titration design was used that was followed by a 3 + 3 dose escalation strategy. Primary objective was assessment of safety. Secondary objectives included determination of PK and objective response rate. Results Seventeen patients were enrolled, of which 8 patients were evaluable for efficacy. Drug-related ≥ Grade 3 treatment-emergent adverse events included abdominal pain, anemia, fatigue, gamma glutamyl-transferase increase, hypertriglyceridemia and vomiting. No dose-limiting toxicity was observed in the 1.0 mg/m2 cohort. The PK data showed that OBP-801 and its active metabolite OBP-801-SH exposure increased proportionally and more than proportionally, respectively. No accumulation of either agent was noticed after repeat administration. Best response was stable disease (37.5%), with one patient each in the three cohorts. Conclusion Further investigations of the OBP-801 1.0 mg/m2 dose will be needed to better understand the efficacy of the agent, either alone or in combination. Trial registration: NCT02414516 (ClinicalTrials.gov) registered on April 10, 2015.

PMID:34613570 | DOI:10.1007/s10637-021-01180-9

Drug Ther Bull. 2021 Oct 5:dtb-2021-000055. doi: 10.1136/dtb.2021.000055. Online ahead of print.

ABSTRACT

Overview of: Hodgkinson JA, Lee MM, Milner S, et al Accuracy of blood-pressure monitors owned by patients with hypertension (ACCU-RATE study): a cross-sectional, observational study in central England. Br J Gen Pract 2020;70:e548-e554.

PMID:34610975 | DOI:10.1136/dtb.2021.000055

Drug Ther Bull. 2021 Oct 5:dtb-2021-000056. doi: 10.1136/dtb.2021.000056. Online ahead of print.

ABSTRACT

Overview of: Azoulay É, Castro P, Maamar A, et al Outcomes in patients treated with chimeric antigen receptor T-cell therapy who were admitted to intensive care (CARTTAS): an international, multicentre, observational cohort study. Lancet Haematol 2021;8:e355-64.

PMID:34610974 | DOI:10.1136/dtb.2021.000056

Reg Anesth Pain Med. 2021 Oct 5:rapm-2021-102984. doi: 10.1136/rapm-2021-102984. Online ahead of print.

NO ABSTRACT

PMID:34610964 | DOI:10.1136/rapm-2021-102984

Ann Geriatr Med Res. 2021 Sep;25(3):217-221. doi: 10.4235/agmr.21.0062. Epub 2021 Sep 29.

ABSTRACT

The consumption of new selective serotonin reuptake inhibitors (SSRIs) is raising dramatically especially in European countries. It contributes to occurrence of clinically important drug side effects. One of which can be hyponatremia. We present two case reports of 85-year-old and 84-year-old women who developed hyponatremia after escitalopram administration. We hypothesize that in both cases hyponatremia was connected with antidepressants administration. However, due to multiple comorbidities and polypharmacy it is often impossible to establish the exact mechanism of hyponatremia. Moreover, it is crucial to distinguish subtypes of drug-induced syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH), such as SSRI-induced SIADH, reset osmostat SIADH, thiazide-associated hyponatremia, thiazide-induced hyponatremia, mineralocorticoid responsive hyponatremia of older adults, in order to properly diagnose and treat geriatric patients. Administration of antidepressants or thiazides should be followed by a regular monitoring of serum sodium level.

PMID:34610667 | DOI:10.4235/agmr.21.0062

JAMA. 2021 Oct 5;326(13):1299-1309. doi: 10.1001/jama.2021.13844.

ABSTRACT

IMPORTANCE: Assessing the scope of acute medication harms to patients should include both therapeutic and nontherapeutic medication use.

OBJECTIVE: To describe the characteristics of emergency department (ED) visits for acute harms from both therapeutic and nontherapeutic medication use in the US.

DESIGN, SETTING, AND PARTICIPANTS: Active, nationally representative, public health surveillance based on patient visits to 60 EDs in the US participating in the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance Project from 2017 through 2019.

EXPOSURES: Medications implicated in ED visits, with visits attributed to medication harms (adverse events) based on the clinicians' diagnoses and supporting data documented in the medical record.

MAIN OUTCOMES AND MEASURES: Nationally weighted estimates of ED visits and subsequent hospitalizations for medication harms.

RESULTS: Based on 96 925 cases (mean patient age, 49 years; 55% female), there were an estimated 6.1 (95% CI, 4.8-7.5) ED visits for medication harms per 1000 population annually and 38.6% (95% CI, 35.2%-41.9%) resulted in hospitalization. Population rates of ED visits for medication harms were higher for patients aged 65 years or older than for those younger than 65 years (12.1 vs 5.0 [95% CI, 7.4-16.8 vs 4.1-5.8] per 1000 population). Overall, an estimated 69.1% (95% CI, 63.6%-74.7%) of ED visits for medication harms involved therapeutic medication use, but among patients younger than 45 years, an estimated 52.5% (95% CI, 48.1%-56.8%) of visits for medication harms involved nontherapeutic use. The proportions of ED visits for medication harms involving therapeutic use were lowest for barbiturates (6.3%), benzodiazepines (11.1%), nonopioid analgesics (15.7%), and antihistamines (21.8%). By age group, the most frequent medication types and intents of use associated with ED visits for medication harms were therapeutic use of anticoagulants (4.5 [95% CI, 2.3-6.7] per 1000 population) and diabetes agents (1.8 [95% CI, 1.3-2.3] per 1000 population) for patients aged 65 years and older; therapeutic use of diabetes agents (0.8 [95% CI, 0.5-1.0] per 1000 population) for patients aged 45 to 64 years; nontherapeutic use of benzodiazepines (1.0 [95% CI, 0.7-1.3] per 1000 population) for patients aged 25 to 44 years; and unsupervised medication exposures (2.2 [95% CI, 1.8-2.7] per 1000 population) and therapeutic use of antibiotics (1.4 [95% CI, 1.0-1.8] per 1000 population) for children younger than 5 years.

CONCLUSIONS AND RELEVANCE: According to data from 60 nationally representative US emergency departments, visits attributed to medication harms in 2017-2019 were frequent, with variation in products and intent of use by age.

PMID:34609453 | DOI:10.1001/jama.2021.13844

Food Funct. 2021 Oct 4;12(19):9443-9455. doi: 10.1039/d1fo01905h.

ABSTRACT

Background: Cyclophosphamide (CYP) is a chemotherapy drug widely used in the treatment of several types of cancers and autoimmune disorders. Unfortunately, it causes severe side effects on many organs due to its oxidative stress effect. Objective: The present study aims to tentatively identify the phytochemical constituents of orange fruit (Citrus sinensis) peel extract (OFPE) and elucidate the chemopreventive effects of OFPE on CYP drug induced organ toxicity. Methods: The high performance liquid chromatography coupled with mass spectroscopy (HPLC-MS/MS) technique was used to identify the compounds. Thirty-five male rats were divided into five groups (GP; n = 7): GP1: normal control, GP2: OFPE 0.5 only, GP3: CYP-only, GP4: OFPE 0.25 + CYP, and GP5: OFPE 0.5 + CYP. Results: Twenty-nine compounds of polyphenolic nature, mainly flavonoids, anthocyanidins, phenolic acids and limonoids were characterized by HPLC-MS/MS analysis. Among these compounds, naringin, hesperidin, diosmin, rutin, neohesperidin and limonin were the predominant compounds in the examined extract. Serum cellular markers were found to be decreased significantly upon treatment with OFPE (especially high dose). Also, a significant prophylactic effect against liver, kidney, and heart injuries induced by CYP via decreasing inflammation (serum TNF-α, IL-1β & IL-6) and lipid peroxidation (MDA) was also revealed. Also, an increase in antioxidant levels (serum TAO, and cellular GSH & CAT in tissue homogenates) confirmed the protective efficacy of OFPE against CYP toxicity. Conclusions: The present study reveals some chemopreventive properties and beneficial effects of OFPE on CYP-induced organ toxicity via its antioxidant status and immunoregulatory activities.

PMID:34606555 | DOI:10.1039/d1fo01905h

Prague Med Rep. 2021;122(3):140-180. doi: 10.14712/23362936.2021.14.

ABSTRACT

Valproate (VPA) was first synthesized in 1882, but it was only in the early 1960s that its anticonvulsant properties were discovered. The aim of this literature review is to evaluate the clinical epidemiological profile, pathological mechanisms, and management of VPA-associated movement disorder (MD). Relevant reports in six databases were identified and assessed by two reviewers without language restriction. A total of 138 reports containing 362 cases of subjects who developed a MD secondary to VPA were reported. The MD identified were parkinsonism (PKN) (252), myoclonus (MCL) (54), dystonia (DTN) (17), dyskinesia (DKN) (16), stutters (4), tics (3), akathisia (AKT) (1). In the not clearly defined group, 15 extrapyramidal symptoms, 3 AKT, 2 DTN, 1 rigidity, 1 unstable gait were assessed. The mean and median age was 55.8 (SD: 16.58) and 61 years (range: 4-87 years). The most common VPA-indication was epilepsy, and 51.36% were males. The mean and median time from the VPA start to the MD onset was 32.75 (SD: 30.05) and 21.15 months (range: 1 day - 20 years). The mean and median time from the VPA withdrawal until the MD recovery was 2.89 (SD: 2.79) and 3 months (1 day - 12 months). The most common management was drug withdrawal. A complete recovery was obtained in 80.61%. VPA-associated MD was extensively reported in the literature. PKN was the most well-described. Future studies need to clearly report the clinical history of the patient, considering the full investigation of other adverse events during their entire life.

PMID:34606429 | DOI:10.14712/23362936.2021.14

Pulm Circ. 2021 Sep 29;11(4):20458940211049300. doi: 10.1177/20458940211049300. eCollection 2021 Oct-Dec.

ABSTRACT

Drug-induced pulmonary arterial hypertension (PAH) is constantly evolving as new drugs are developed. Carfilzomib is a recently approved therapy for relapsed and refractory multiple myeloma. While it has been associated with cardiovascular adverse events, such as ischemic heart disease and heart failure, PAH has not been a well-described side effect. We present two patients who developed PAH associated with initiation of carfilzomib. They both initially presented with severe dyspnea, had elevated right ventricular systolic pressure on transthoracic echocardiography and ultimately underwent right heart catheterization. With discontinuation of carfilzomib, both patients had improvement in hemodynamics. However, one patient required initiation of PAH-targeted therapies and has had worsening right ventricular function again despite permanent discontinuation of carfilzomib. It is important to recognize the association between carfilzomib and PAH. Echocardiography can be an important initial screening tool. PAH from carfilzomib therapy may be reversible, especially if diagnosed early; however, extended follow-up is essential.

PMID:34603687 | PMC:PMC8485285 | DOI:10.1177/20458940211049300

J Nepal Health Res Counc. 2021 Sep 6;19(2):362-366. doi: 10.33314/jnhrc.v19i2.3509.

ABSTRACT

BACKGROUND: Different bowel preparation regimens are available. Currently we are giving the entire preparation on the day of colonoscopy. Multiple studies have shown splitting the regimen might improve the quality of bowel preparation with lesser side effects and better compliance. The study was done to compare the efficacy and tolerability of split bowel preparation regimen with non-split dosing regimen.

METHODS: Single centered observational comparative study was done in a tertiary care hospital. One hundred ninety eight patients requiring elective colonoscopy were assigned to receive one of the two preparations (split versus morning) prior to colonoscopy. Main outcomes were bowel preparation quality and patient compliance and tolerability.

RESULTS: There was no significant difference between the two regimen for the mean total Boston Bowel Preparation Scale (6.79VS 6.74,P value -0.777).Patient compliance was better for split dosing compared to single dosing (99 vs 5 p value-<0.001).There were more side effects in the single dosage compared to split dosing except for sleep disturbance which was more in split dosing.

CONCLUSIONS: The study found that split-dose and single dose polyethylene glycol solution for bowel preparation before colonoscopy had similar efficacy in the quality of bowel preparation. Split-dose polyethylene glycol appears to be superior to single-dose PEG for patient compliance and side effects.

PMID:34601531 | DOI:10.33314/jnhrc.v19i2.3509

Orv Hetil. 2021 Oct 3;162(40):1610-1618. doi: 10.1556/650.2021.32223.

ABSTRACT

Összefoglaló. A dohányzás jelenleg is az egyik legjelentősebb népegészségügyi probléma hazánkban. Az orvosi szakterületek többségében előkerül a dohányzásleszokás-támogatás kérdése. Ezért az orvostársadalom számára az aktuális gyógyszeres terápiás ismeretek összefoglalása hasznos lehet. A jelen közleményben a leszokástámogatás elsődlegesen választandó gyógyszeres terápiáját tekintjük át a legújabb összefoglalók és irányelvek szerint. A gyógyszeres lehetőségek közül jelenleg a vareniklin és a nikotinpótló terápia választandó elsőként, nemcsak a leszokás, hanem az ártalomcsökkentés tekintetében is. A legújabb kutatási eredmények szerint a kis dózisú vareniklin hatékonysága megközelíti a standard adagolás hatékonyságát, ugyanakkor kevesebb mellékhatás jelentkezik. A nikotinpótló kezeléssel kapcsolatban ki kell emelni, hogy egyre több tudományos evidencia áll a transdermalis és oralis készítmények kombinálása mellett, szemben a monoterápiával. A kis dózisú vareniklin, illetve a nikotinpótló terápia akkor is segítséget nyújt a naponta elszívott cigaretták mérséklésében, ha a kliens nem kíván leszokni, de a dohányzás ártalmait csökkentené. A nikotinerg rendszeren kívül más módon ható gyógyszerek szerepe is felmerült. Egyre több összefoglaló támogatja az antidepresszívumok használatát a nikotinfüggőség kezelésében. Ezek közül a bupropion használatával kapcsolatban van a legtöbb adat, amelyről tudjuk, hogy kombinálható a nikotinpótló terápiával és a vareniklinnel is. A gyógyszeres terápiát minden esetben tanácsos magatartásorvoslási módszerekkel, illetve adherenciát fokozó intervenciókkal kombinálni. Ezenkívül a szakellátási szint bevonása is javasolt, hogy a lehető legtöbb segítséget kapja meg a páciens a leszokáshoz. Orv Hetil. 2021; 162(40): 1610-1618. Summary. Smoking is still one of the most significant public health problems in Hungary. The issue of smoking cessation support comes up in most medical specialties. Therefore, a summary of the current pharmacotherapeutic knowledge may prove useful to the medical community. In this paper, we review the first-line pharmacotherapy for smoking cessation based on the latest summaries and guidelines. Regarding the smoking cessation agents, varenicline and nicotine replacement therapy are currently the primary choice, not only in terms of cessation but also in terms of harm reduction. The results of previous studies suggest that the efficacy of low dose varenicline is close to that of standard dosing, with fewer side effects. With regard to nicotine replacement therapy, it should be emphasized that there is an increasing scientific evidence for the combination of transdermal and oral formulations as opposed to monotherapy. Low dose varenicline and nicotine replacement therapy also help reduce the number of cigarettes smoked daily if the client does not want to quit but would reduce the harms of smoking. The role of medications acting in other ways than the nicotinergic system has also emerged. An increasing number of reviews support the use of antidepressants in the treatment of nicotine addiction. Of these, most data are available on the use of bupropion, which is known to be combined with nicotine replacement therapy and varenicline. In all cases, it is advisable to combine pharmacotherapy with behavioral therapy as well as interventions that increase adherence. In addition, it is also recommended to include specific therapeutic interventions in order to get as much help as possible for the patient to quit smoking. Orv Hetil. 2021; 162(40): 1610-1618.

PMID:34601458 | DOI:10.1556/650.2021.32223

BMC Health Serv Res. 2021 Oct 2;21(1):1042. doi: 10.1186/s12913-021-07025-8.

ABSTRACT

BACKGROUND: Genetic testing has potential roles in identifying whether an individual would have risk of adverse drug reactions (ADRs) from a particular medicine. Robust cost-effectiveness results on genetic testing would be useful for clinical practice and policy decision-making on allocating resources effectively. This study aimed to update a systematic review on economic evaluations of pharmacogenetic testing to prevent ADRs and critically appraise the quality of reporting and sources of evidence for model input parameters.

METHODS: We searched studies through Medline via PubMed, Scopus and CRD's NHS Economic Evaluation up to October 2019. Studies investigating polymorphism-based pharmacogenetic testing, which guided drug therapies to prevent ADRs, using economic evaluation methods were included. Two reviewers independently performed data extraction and assessed the quality of reporting using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) guidelines and the quality of data sources using the hierarchy of evidence developed by Cooper et al. RESULTS: Fifty-nine economic evaluations of pharmacogenetic testing to avoid drug-induced ADRs were found between 2002 and 2018. Cost-utility and cost-effectiveness analyses were the most common methods of economic evaluation of pharmacogenetic testing. Most studies complied with the CHEERS checklist, except for single study-based economic evaluations which did not report uncertainty analysis (78%). There was a lack of high-quality evidence not only for estimating the clinical effectiveness of pharmacogenetic testing, but also baseline clinical data. About 14% of the studies obtained clinical effectiveness data of testing from a meta-analysis of case-control studies with direct comparison, which was not listed in the hierarchy of evidence used.

CONCLUSIONS: Our review suggested that future single study-based economic evaluations of pharmacogenetic testing should report uncertainty analysis, as this could significantly affect the robustness of economic evaluation results. A specific ranking system for the quality of evidence is needed for the economic evaluation of pharmacogenetic testing of ADRs. Differences in parameters, methods and outcomes across studies, as well as population-level and system-level differences, may lead to the difficulty of comparing cost-effectiveness results across countries.

PMID:34600523 | DOI:10.1186/s12913-021-07025-8

Lancet Oncol. 2021 Sep 30:S1470-2045(21)00402-2. doi: 10.1016/S1470-2045(21)00402-2. Online ahead of print.

ABSTRACT

BACKGROUND: The majority of patients with metastatic castration-resistant prostate cancer (mCRPC) will have disease progression of a uniformly fatal disease. mCRPC is driven by both activated androgen receptors and elevated intratumoural androgens; however, the current standard of care is therapy that targets a single androgen signalling mechanism. We aimed to investigate the combination treatment using apalutamide plus abiraterone acetate, each of which suppresses the androgen signalling axis in a different way, versus standard care in mCRPC.

METHODS: ACIS was a randomised, placebo-controlled, double-blind, phase 3 study done at 167 hospitals in 17 countries in the USA, Canada, Mexico, Europe, the Asia-Pacific region, Africa, and South America. We included chemotherapy-naive men (aged ≥18 years) with mCRPC who had not been previously treated with androgen biosynthesis signalling inhibitors and were receiving ongoing androgen deprivation therapy, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and a Brief Pain Inventory-Short Form question 3 (ie, worst pain in the past 24 h) score of 3 or lower. Patients were randomly assigned (1:1) via a centralised interactive web response system with a permuted block randomisation scheme (block size 4) to oral apalutamide 240 mg once daily plus oral abiraterone acetate 1000 mg once daily and oral prednisone 5 mg twice daily (apalutamide plus abiraterone-prednisone group) or placebo plus abiraterone acetate and prednisone (abiraterone-prednisone group), in 28-day treatment cycles. Randomisation was stratified by presence or absence of visceral metastases, ECOG performance status, and geographical region. Patients, the investigators, study team, and the sponsor were masked to group assignments. An independent data-monitoring committee continually monitored data to ensure ongoing patient safety, and reviewed efficacy data. The primary endpoint was radiographic progression-free survival assessed in the intention-to-treat population. Safety was reported for all patients who received at least one dose of study drug. This study is completed and no longer recruiting and is registered with ClinicalTrials.gov, number NCT02257736.

FINDINGS: 982 men were enrolled and randomly assigned from Dec 10, 2014 to Aug 30, 2016 (492 to apalutamide plus abiraterone-prednisone; 490 to abiraterone-prednisone). At the primary analysis (median follow-up 25·7 months [IQR 23·0-28·9]), median radiographic progression-free survival was 22·6 months (95% CI 19·4-27·4) in the apalutamide plus abiraterone-prednisone group versus 16·6 months (13·9-19·3) in the abiraterone-prednisone group (hazard ratio [HR] 0·69, 95% CI 0·58-0·83; p<0·0001). At the updated analysis (final analysis for overall survival; median follow-up 54·8 months [IQR 51·5-58·4]), median radiographic progression-free survival was 24·0 months (95% CI 19·7-27·5) versus 16·6 months (13·9-19·3; HR 0·70, 95% CI 0·60-0·83; p<0·0001). The most common grade 3-4 treatment-emergent adverse event was hypertension (82 [17%] of 490 patients receiving apalutamide plus abiraterone-prednisone and 49 [10%] of 489 receiving abiraterone-prednisone). Serious treatment-emergent adverse events occurred in 195 (40%) patients receiving apalutamide plus abiraterone-prednisone and 181 (37%) patients receiving abiraterone-prednisone. Drug-related treatment-emergent adverse events with fatal outcomes occurred in three (1%) patients in the apalutamide plus abiraterone-prednisone group (2 pulmonary embolism, 1 cardiac failure) and five (1%) patients in the abiraterone-prednisone group (1 cardiac failure and 1 cardiac arrest, 1 mesenteric arterial occlusion, 1 seizure, and 1 sudden death).

INTERPRETATION: Despite the use of an active and established therapy as the comparator, apalutamide plus abiraterone-prednisone improved radiographic progression-free survival. Additional studies to identify subgroups of patients who might benefit the most from combination therapy are needed to further refine the treatment of mCRPC.

FUNDING: Janssen Research & Development.

PMID:34600602 | DOI:10.1016/S1470-2045(21)00402-2

Acta Gastroenterol Belg. 2021 Jul-Sep;84(3):497-499. doi: 10.51821/84.3.015.

ABSTRACT

Pneumatosis Intestinalis (PI) is a rare radiological finding defined as the presence of extra-luminal gas within the intestinal wall. Several anti-tumor drugs can induce a damage of the gastrointestinal walls as an adverse effect, causing loss of mucosal integrity and endoluminal gas diffusion, responsible for PI development. We retrospectively analyzed 8 cases of PI detected through radiological imaging in oncologic patients undergoing various therapeutic regimens: five patients were receiving chemotherapy, two molecular targeted therapy (MTT) and one immunotherapy. Three patients were asymptomatic and pneumatosis was incidentally detected at routinary follow-up CT and then treated conservatively. Five patients presented acute abdomen symptoms and in these cases bowel perforation was the cause of death. Our experience confirms PI and perforation as rare complications of drug toxicity, especially in oncologic patients treated with combinations of different anticancer drugs and documented the second reported case of PI associated with atezolizumab and alectinib single administration.

PMID:34599575 | DOI:10.51821/84.3.015

J Clin Oncol. 2021 Oct 1:JCO2100468. doi: 10.1200/JCO.21.00468. Online ahead of print.

ABSTRACT

PURPOSE: The activity of androgen-deprivation therapy (ADT) in androgen receptor-positive (AR+) salivary gland carcinomas (SGCs) has been established in the past few years. Second-line treatment in castration-resistant patients is still unknown. We investigated the activity of abiraterone acetate as second-line treatment in ADT-resistant, AR+ patients with SGC.

METHODS: This was a single-institution phase II trial. A two-stage Simon's design was applied. The primary end point was confirmed objective response rate. Secondary end points were disease control rate, safety, progression-free survival, and overall survival. Patients were eligible when the following criteria were met: histologic diagnosis of AR-overexpressing SGC, measurable disease according to RECIST 1.1, clinical and/or radiologic progression on ADT, suppressed serum testosterone, and no limits for the number of previous chemotherapy lines. All patients received abiraterone 1 g daily plus prednisone 10 mg and luteinizing hormone-releasing hormone agonist until progression or unacceptable toxicities.

RESULTS: From 2015 to 2019, 24 AR+ patients with SGC (23 men; median age 65.8 years) were treated within the study. The overall response rate was 21% (5 partial responses), with a disease control rate of 62.5%. The median duration of response was 5.82 months. Median progression-free survival was 3.65 months (95% CI, 1.94 to 5.89), and median overall survival was 22.47 months (95% CI, 6.74 to not reached). Objective response to previous ADT did not correlate with the activity of abiraterone. Adverse events (AEs) were recorded in 22 cases (92%) with grade 3 AEs in six patients (25%): fatigue (two), flushing (one), supraventricular tachycardia (one), and two non-drug-related AEs. No drug-related grade 4 or 5 AEs were recorded.

CONCLUSION: Abiraterone plus luteinizing hormone-releasing hormone agonist is active and safe as a second-line option in AR-expressing, castration-resistant SGC.

PMID:34597119 | DOI:10.1200/JCO.21.00468