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Evaluation of miR-122 to Predict High Dose Acetaminophen-Induced Liver Injury in Mice: The Combination Uses of 5-Fluorouracil.

Biol Pharm Bull. 2018;41(11):1732-1735

Authors: Munakata C, Fuchigami Y, Hiroishi S, Haraguchi A, Hagimori M, Enomoto H, Tachiki H, Kodama Y, Sasaki H, Kawakami S

Abstract
Administration of high doses of acetaminophen (APAP) is known to cause drug-induced liver injury (DILI) in humans. Therefore, the detection or prediction of these side-effects at an early stage using appropriate biomarkers is the need of the hour. Micro RNA (miR)-122 is expected to be a novel biomarker for liver injury. However, more evidence is required in various alternate situations such as its use in combination as APAP is often used along with anticancer drugs. In the present study, we aimed to evaluate the functions of miR-122 as a biomarker for liver injury in comparison with alanine aminotransferase (ALT) in a mice model with the APAP-induced liver injury (AILI). Consequently, there was a dose-dependent increase in miR-122 after administration of APAP intraperitoneally. Similar observations were made for ALT activity. Additionally, the expression of miR-122 increased in a more rapid manner compared to ALT activity. However, there was a variation in the miR-122 expression. Further, we investigated the drug-drug interaction between APAP and 5-fluorouracil using miR-122 and ALT in mice. As a result, the degree of AILI was not changed by the use of 5-fluorouracil in combination with APAP in mice.

PMID: 30381674 [PubMed - in process]

[Analysis of Risk Factors for Side Effects and the Establishment of Supportive Therapy during Cancer Chemotherapy].

Yakugaku Zasshi. 2018;138(11):1363-1370

Authors: Sakurada T

Abstract
Cancer chemotherapy has a high frequency of side effects, and patients often experience adverse health effects. This review focuses on risk factors and supportive care for the prevention of chemotherapy side effects. 1) Drug-induced interstitial lung disease (DILD) is one of the serious adverse events associated with chemotherapy, and this retrospective study investigated the risk of DILD in Japanese patients with lung cancer. Among the 459 patients who received lung cancer chemotherapy from April 2007 to March 2013, 33 (7.2%) developed chemotherapy-associated DILD. Preexisting interstitial lung disease was a risk factor for DILD [odds ratio (OR)=5.38; 95% confidence interval (CI)=2.47-11.73]. Early death was observed in 10 of the 33 patients who developed DILD. Epidermal growth factor receptor-tyrosine kinase inhibitor use (OR=9.26; 95%CI=1.05-81.96) and two or more prior chemotherapy regimens (OR=6.95; 95%CI=1.14-42.35) were identified as poor prognostic factors. 2) The incidence of pemetrexed-induced rash is high. The aim of this retrospective study was to evaluate the efficacy of corticosteroids for pemetrexed-induced rash. Rash developed in 26.9% of patients who received pemetrexed between April 2009 and March 2014. Supplementation with dexamethasone (≥1.5 mg) on days 2 and 3 significantly reduced the incidence of rash compared with no supplementary corticosteroids (39.4% vs. 17.8%, p<0.05). Increasing the corticosteroid dose had no additional effect on pemetrexed-induced rash development. These results suggest that supplementary corticosteroids may prevent pemetrexed-induced rash, and low-dose corticosteroids are sufficient for such prevention.

PMID: 30381644 [PubMed - in process]

Bosentan for patients with steroid-resistant pulmonary sarcoidosis: a randomised controlled trial.

Swiss Med Wkly. 2018 Oct 22;148:w14677

Authors: Hostettler K, Baty F, Kleiner R, Junker L, Tamm M, Brutsche M

Abstract
BACKGROUND: Sarcoidosis is a disorder of unknown aetiology. Most patients have steroid-responsive disease, but side effects and steroid resistance may necessitate alternative treatments. Endothelin has in-vitro fibrogenic activity and the endothelin system is activated in sarcoidosis.
OBJECTIVES: We studied the efficacy and safety of the endothelin receptor antagonist bosentan in sarcoidosis patients.
METHODS: In a prospective 12-month, double-blind, 1:1-randomised, placebo-controlled phase II trial, we assessed the effect of bosentan in patients with steroid-resistant sarcoidosis and with impaired exercise capacity and/or resting lung function. Primary endpoints were safety and overall response rate of total lung capacity, diffusion capacity, peak oxygen uptake, 6-minute walking distance and chest computed tomography score. Secondary endpoints included adverse events and quality of life.
MAIN RESULTS: Twenty patients were randomised. Three patients discontinued the study medication prematurely. No serious drug-related adverse events occurred. At 12 months no statistically significant differences were observed in the primary endpoints including total lung capacity, diffusion capacity, 6-minute walking distance, peak oxygen uptake, and computed tomography-score. Sixty-three percent of the patients treated with bosentan showed an increase of 10% in at least one of the primary endpoints, compared with 67% in the placebo group (p = 1).
CONCLUSIONS: There is no evidence to support efficacy of bosentan as an antifibrotic treatment for patients with steroid-resistant pulmonary sarcoidosis. Bosentan was well tolerated and no drug-related adverse effects were observed within the study population.
TRIAL REGISTRATION: ISRCTN registry, ISRCTN73579020.

PMID: 30378090 [PubMed - in process]

Rationale and design of the Caloric Restriction and Exercise protection from Anthracycline Toxic Effects (CREATE) study: a 3-arm parallel group phase II randomized controlled trial in early breast cancer.

BMC Cancer. 2018 Sep 03;18(1):864

Authors: Kirkham AA, Paterson DI, Prado CM, Mackey JM, Courneya KS, Pituskin E, Thompson RB

Abstract
BACKGROUND: Anthracycline chemotherapy agents are commonly used to treat breast cancer, but also result in cardiac injury, and potentially detrimental effects to vascular and skeletal muscle. Preclinical evidence demonstrates that exercise and caloric restriction can independently reduce anthracycline-related injury to the heart as well as cancer progression, and may be promising short-term strategies prior to treatment administration. For women with breast cancer, a short-term strategy may be more feasible and appealing, as maintaining regular exercise training or a diet throughout chemotherapy can be challenging due to treatment symptoms and psychosocial distress.
METHODS: The Caloric Restriction and Exercise protection from Anthracycline Toxic Effects (CREATE) study will determine whether acute application of these interventions shortly prior to receipt of each treatment can reduce anthracycline-related toxicity to the heart, aorta, and skeletal muscle. Fifty-six women with early stage breast cancer scheduled to receive anthracycline treatment will be randomly assigned to one of three groups who will: 1) perform a single, 30-min, vigorous-intensity, aerobic exercise session 24 h prior to each anthracycline treatment; 2) consume a prepared diet reduced to 50% of caloric needs for 48 h prior to each anthracycline treatment; or 3) receive usual cancer care. The primary outcome is magnetic resonance imaging (MRI) derived left ventricular ejection fraction reserve (peak exercise LVEF - resting LVEF) at the end of anthracycline treatment. Secondary outcomes include MRI-derived measures of cardiac, aortic and skeletal muscle structure and function, circulating NT-proBNP, cardiorespiratory fitness and treatment symptoms. Exploratory outcomes include quality of life, fatigue, tumor size (only in neoadjuvant patients), oxidative stress and antioxidants, as well as clinical cardiac or cancer outcomes. MRI, exercise tests, and questionnaires will be administered before, 2-3 weeks after the last anthracycline treatment, and one-year follow-up.
DISCUSSION: The proposed lifestyle interventions are accessible, low cost, drug-free potential methods for mitigating anthracycline-related toxicity. Reduced toxic effects on the heart, aorta and muscle are very likely to translate to short and long-term cardiovascular health benefits, including enhanced resilience to the effects of subsequent cancer treatment (e.g., radiation, trastuzumab) aging, and infection.
TRIAL REGISTRATION: ClinicalTrials.gov NCT03131024; 4/21/18.

PMID: 30176834 [PubMed - indexed for MEDLINE]

A comparative phase III clinical study to evaluate efficacy and safety of TrastuRel™ (biosimilar trastuzumab) and innovator trastuzumab in patients with metastatic human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer.

Indian J Cancer. 2017 Oct-Dec;54(4):664-668

Authors: Apsangikar P, Chaudhry S, Naik M, Deoghare S, Joseph J

Abstract
INTRODUCTION: The present study for biosimilar trastuzumab was a multicentric, randomized, two-arm parallel-group, comparative phase III study in patients with metastatic breast cancer.
MATERIALS AND METHODS: Stage I of the study was conducted among 42 participants with equal distribution in the study and reference arm. After a loading dose of 8 mg/kg trastuzumab was administered intravenously on day 1 of the first cycle; serum samples were obtained at 0, 1.5 (end of IP infusion), 3, 6, 8, 24, 96, 168, and 336 h after the first infusion for the first cycle only. Cmax and AUC0-336 were calculated for a single dose. Stage II enrolled a total of 106 patients across 20 centers who were randomized to receive biosimilar trastuzumab (study trastuzumab) or the reference trastuzumab with paclitaxel. The primary endpoint of the objective response rate (ORR) was analyzed after last the dosed participant had completed 25-week evaluation. The secondary outcome measures included time to tumor progression, progression-free survival and overall survival at week 48, and safety evaluation.
RESULTS: For reference and study trastuzumab products, mean Cmax of 229.02 and 210.68 μg/mL and AUC0-336 of 24298.29 and 25809.33 (μg × h/mL), respectively, were obtained. The efficacy results demonstrated that study trastuzumab and reference trastuzumab had comparable ORR (48.44% vs. 44.44%). The proportions of participants showing complete response and partial response in each arm were found to be comparable. There were 56 (68.29%) participants in the study arm and 13 (59.09%) participants in the reference arm who had at least one adverse event during the study. Immunogenicity assessment also revealed no participants with positive antibody titer in any of the study arms.
CONCLUSION: The pharmacokinetics, overall response rate at 25 weeks, and safety of the biosimilar trastuzumab was comparable to the reference trastuzumab.

PMID: 30082554 [PubMed - indexed for MEDLINE]

First-line tyrosine kinase inhibitors in metastatic renal cell carcinoma: A regional cancer center experience.

Indian J Cancer. 2017 Oct-Dec;54(4):626-630

Authors: Rudresha AH, Chaudhuri T, Lakshmaiah KC, Babu GK, Lokanatha D, Jacob LA, Suresh Babu MC, Lokesh KN, Rajeev LK

Abstract
BACKGROUND: Renal cell carcinoma (RCC) is highly resistant to systemic chemotherapy, and historically a poor prognosis for metastatic disease has been reported, with a 5-year survival rate of <10%. Significant advances have been made in the last decade since the introduction of different tyrosine kinase inhibitors (TKIs) such as sunitinib, pazopanib, and sorafenib. Unfortunately, even though the TKIs have been used for a long time, there are very few published data regarding the experience of TKI therapy in metastatic RCC (mRCC) from India.
MATERIALS AND METHODS: This is a single institutional review of mRCC patients treated between January 2012 and July 2017. Patients who received at least 1 month of first-line TKIs were included for analysis of response rates, toxicity, survival outcomes, and prognostic factors.
RESULTS: Of the 40 mRCC patients, 31 (77.5%) were males. Median age at diagnosis was 58 years (range: 38-80 years). The most common site of metastasis was lungs (n = 24) followed by bone (n = 19) and liver (n = 7). Three patients had favorable risk disease, whereas 25 had intermediate risk and 12 had poor risk disease according to the MSKCC risk criteria. First-line TKI therapy used was sunitinib in 24, pazopanib in 11, and sorafenib in 5 patients. Toxicities of TKIs were Grade 1 or 2 in 13 patients and Grade 3 or 4 in 9 patients; the most common being fatigue, followed by hand-foot syndrome, skin rash, mucositis, and hypertension. Overall, 29 patients (72.5%) had disease control (complete responses in 1, partial responses in 10, and stable disease in 18 patients), whereas 11 had progression of disease at initial evaluation. At a median follow-up of 16 months (range: 2-38 months), median progression-free survival (PFS) was 10.8 months and median overall survival was 19.1 months.
CONCLUSIONS: Sunitinib and pazopanib are viable first-line options for mRCC and showed a comparable PFS in Indian patients. Careful patient selection, tailoring of TKI doses, and careful toxicity management are essential for optimum therapy.

PMID: 30082547 [PubMed - indexed for MEDLINE]

Effective assessment of psychotropic medication side effects using PsyLOG mobile application.

Schizophr Res. 2018 02;192:211-212

Authors: Rojnic Kuzman M, Andlauer O, Burmeister K, Dvoracek B, Lencer R, Koelkebeck K, Maric NP, Nawka A, Pantovic-Stefanovic M, Riese F, Aukst Margetic B, Bosnjak D, Ruzic MC, Curkovic M, Grubsin J, Madzarac Z, Makaric P, Petric D, Radic K, Savic A

PMID: 28457773 [PubMed - indexed for MEDLINE]

Effect of valaciclovir on CD4 count decline in untreated HIV: an international randomized controlled trial.

J Antimicrob Chemother. 2018 Oct 29;:

Authors: Tan DHS, Raboud JM, Szadkowski L, Grinsztejn B, Madruga JV, Figueroa MI, Cahn P, Barton SE, Clarke A, Fox J, Zubyk W, Walmsley SL, VALIDATE Study Group

Abstract
Objectives: To determine the impact of valaciclovir on HIV disease progression in treatment-naive HIV-positive adults.
Methods: In this fully blind, multicentre, 1:1 randomized placebo-controlled trial, treatment-naive HIV-1-positive adults with CD4 counts 400-900 cells/mm3 and not meeting contemporaneous recommendations for combination ART (cART) were randomized to valaciclovir 500 mg or placebo twice daily, and followed quarterly until having two consecutive CD4 counts ≤350 cells/mm3 or initiating cART for any reason. The primary analysis compared the rate of CD4 count decline by study arm after adjusting for baseline CD4 count and viral load (VL). Secondary analyses compared the rate of CD4 percentage decline, HIV VL, herpes simplex virus (HSV) recurrences and drug-related adverse events. The trial closed after release of the START trial results in August 2015.
Results: We enrolled 198 participants in Canada, Brazil, Argentina and the UK. Median (IQR) age was 35 (30-43) years. Baseline CD4 count was 592 (491-694) cells/mm3 and VL was 4.04 (3.5-4.5) log10 copies/mL. Over 276 person-years of follow-up, CD4 counts declined by 49 cells/mm3/year in the valaciclovir arm versus 58 cells/mm3/year in the placebo arm (P = 0.65). No differences were seen in the rate of change in CD4 percentage (-1.2%/year versus -1.7%/year, P = 0.34). VL was 0.27 log10 copies/mL lower in valaciclovir participants overall (P<0.001). Placebo participants had more HSV recurrences (62 versus 21/100 person-years, P < 0.0001) but similar rates of grade ≥2 drug-related adverse events.
Conclusions: Unlike prior trials using aciclovir, we found that valaciclovir did not slow CD4 count decline in cART-untreated adults, although power was limited due to premature study discontinuation. Valaciclovir modestly lowered HIV VL.

PMID: 30376108 [PubMed - as supplied by publisher]

Advanced signet-ring cell carcinoma of the stomach: Clinicopathological characteristics of patients and efficacy of the modified docetaxel, cisplatin, and fluorouracil regimen.

J Cancer Res Ther. 2018 Sep;14(Supplement):S742-S747

Authors: Bozkaya Y, Erdem GU, Özdemir NY, Hocazade C, Yazici O, Demirci NS, Zengin N

Abstract
Background: The aim of this retrospective study was to investigate the clinicopathological characteristics of patients with signet-ring cell carcinoma (SRCC) of the stomach, and the efficacy of the modified docetaxel, cisplatin, and fluorouracil (mDCF) chemotherapy regimen.
Patients and Methods: Sixty-five patients diagnosed with metastatic or recurrent SRCC and treated with at least one course of mDCF regimen as the first-line treatment at our hospital July 2007 and January 2015, were included in this study. The mDCF protocol comprised docetaxel at 60 mg/m2/day (day 1), cisplatin at 60 mg/m2/day (day 1), and 5-fluorouracil at 600 mg/m2/day (days 1-5) for every 3 weeks.
Results: The median age was 53 years (range, 25-69 years). The most frequent sites of metastasis were the peritoneum (50.8%) and liver (21.5%). The median number of chemotherapy courses was six. In assessing 61 patients for response evaluation, one patient (1.6%) achieved a complete response, and 36 (59.0%) achieved a partial response. Fifteen patients (24.6%) had stable disease and nine (14.8%) had progressive disease. Grades 3-4 hematological toxicity revealed anemia in three (4.6%) patients, thrombocytopenia in two (3.1%), and neutropenia in five (7.7%). Grades 3-4 nonhematological side effects revealed nausea and vomiting in four (6.1%) patients and mucositis in one (1.5%). The overall survival (OS) and progression-free survival (PFS) were 10.4 months (95% confidence interval [95% CI], 8.9-12.0) and 6.1 months (95% CI, 5.1-7.0), respectively. Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) performance score of 2 and a high pretreatment carcinoembryonic antigen level were statistically significant.
Conclusions: mDCF is an effective regimen in patients with SRCC of the stomach who have ECOG performance score of 0-1 when the PFS, OS, and tumor response rate are considered. Further prospective studies including more patients should be conducted on this subject.

PMID: 30249897 [PubMed - indexed for MEDLINE]

Evaluation of the use of nab-paclitaxel and gemcitabine in clinical practice.

J Cancer Res Ther. 2018 Sep;14(Supplement):S730-S735

Authors: Casanova-Martinez C, Romero-Ventosa EY, González-Costas S, Arroyo-Conde C, Piñeiro-Corrales G

Abstract
Context: Pancreatic cancer in a common tumor in our country for which there are various treatment alternatives.
Objective: Evaluate the effectiveness and safety of nab-paclitaxel and gemcitabine in everyday clinical practice.
Settings and Design: Observational, retrospective study at a tertiary university hospital.
Subjects and Methods: We included patients diagnosed of metastatic or locally advanced pancreatic cancer that were being treated with nab-paclitaxel and gemcitabine. We recorded response, progression-free survival (PFS), and overall survival (OS) rates together with toxicities.
Statistical Analysis Used: We used SPSS program for Windows. We conducted descriptive statistics using averages, medians, standard deviations or ranges, and percentages.
Results: We included 15 patients. At 3 months, there were no complete responses; 20% showed partial responses, and in 60% of patients, the disease stabilized. The median PFS was 8.9 months and the OS was 9.6. The most important adverse reactions were neutropenia, fatigue, and nausea/vomiting.
Conclusions: The treatment regimen leads to increased survival in these patients with an acceptable toxicity profile.

PMID: 30249895 [PubMed - indexed for MEDLINE]

Drug-induced uveitis.

Curr Opin Ophthalmol. 2018 Nov;29(6):588-603

Authors: Moorthy RS, Moorthy MS, Cunningham ET

Abstract
PURPOSE OF REVIEW: Nearly one-half of all uveitis cases seen at tertiary referral centers have no identifiable cause. Many systemic, paraocular, intraocular, topical medications, and even vaccines can induce intraocular inflammation, scleritis, and rarely orbititis and are often overlooked as causes of uveitis. This review was undertaken to elucidate the strength of association of these medications with uveitis and to make clinicians aware of these associations, especially among newer medications.
RECENT FINDINGS: Medication-induced uveitis has become particularly important and more frequently seen because of the advent of biologic therapies such as immune checkpoint inhibitors (ICPIs), BRAF, and MEK inhibitors, antivascular endothelial growth factor agents, and antitumor necrosis factor agents, as well as newer systemic bisphosphonates are strongly associated with uveitis.
SUMMARY: The ever-broadening scope of pharmaceuticals now available to treat previously untreatable conditions, such as advanced metastatic cutaneous melanoma, have resulted in unintended ocular inflammatory diseases. Ophthalmologists must recognize that drugs such as ICPIs, BRAF, and MEK inhibitors, anti-vascular endothelial growth factor agents, tumor necrosis factor-α inhibitors, cidofovir, bisphosphonates, topical prostaglandin analogues, topical brimonidine, BCG vaccination can cause of uveitis. Utilizing a thorough review of systems, physicians may readily identify medications that may cause uveitis and avoid expensive and unnecessary laboratory testing.

PMID: 30222658 [PubMed - indexed for MEDLINE]

Efficacy and safety of everolimus in hormone receptor positive breast cancer in a developing country: Real-life single institutional experience.

J Cancer Res Ther. 2018 Jul-Sep;14(5):1112-1116

Authors: Assi T, Kattan J, El Rassy E, Tabchi S, Chebib R, Moussa T, Hanna C, El Karak F, Farhat F, Ghosn M

Abstract
Introduction: Breast cancer is the second leading cause of cancer-related mortality despite the staggering improvement in cancer therapeutics. So far, published data illustrate endocrine therapy as the cornerstone treatment for patients with hormone receptor-positive metastatic breast cancer. Unfortunately, most patients eventually develop resistance to this treatment.
Methods: The purpose of this study is to evaluate the efficacy of mammalian target of rapamycin inhibition in reversing hormone resistance in the Lebanese breast cancer patients. Efficacy of the intervention according to the independent factors and notable side effects encountered were the primary points of the evaluation.
Results: In total, fifty patients received the combination of everolimus and exemestane. The mean age of the study population was 61 ± 11 years. Sensitivity to hormonal therapy before the start of the combination treatment was estimated at 64%. Response rate was 14%, and all patients were partial responders. After regular interval evaluation, the median progression-free survival was 5.2 months since the initiation of therapy. The main toxicities associated with the combination were stomatitis (22%), myalgia (22%), skin toxicity (8%), and hyperglycemia (4%), all Grades 1 and 2.
Conclusion: Everolimus has been shown to be effective in overcoming hormonal resistance in Lebanese breast cancer patients with results inferior to those reported in the BOLERO-2 population. The particular differences in molecular and pathological aspects of breast cancer in our region should stimulate the extensive research for a better understanding of the particular pattern of the disease.

PMID: 30197358 [PubMed - indexed for MEDLINE]

Auditory function and quality of life in patients receiving cisplatin chemotherapy in head and neck cancer: A case series follow-up study.

J Cancer Res Ther. 2018 Jul-Sep;14(5):1099-1104

Authors: Kalyanam B, Sarala N, Azeem Mohiyuddin SM, Diwakar R

Abstract
Background: Cisplatin is one of the anticancer drugs used for head and neck cancers. Although some studies have shown that cisplatin can cause ototoxicity, periodic audiometric assessments have not been extensively studied in the Indian rural population. Hence, this study has been undertaken to evaluate the effects of cisplatin on hearing.
Materials and Methods: Fifty-nine patients with squamous cell carcinomas of head and neck, who received cisplatin chemotherapy, were recruited. Serum creatinine, blood urea, serum proteins, and audiometry were assessed before and after the first, second, and third chemotherapy cycle. The cochleotoxic effect of cisplatin was assessed by pure tone audiometry. Hearing loss was graded accordingly. All patients were administered a quality of life questionnaire at baseline and at the end of the third cycle.
Results: Hearing loss was observed in 12 patients at speech frequencies and those at higher frequencies were 12 (4000 Hz), 18 (6000 Hz), and 28 (8000 Hz). The hearing loss was symmetrical, sensorineural, and showed a strong correlation with the low serum albumin levels at the end of the third cycle. Dizziness was seen in eight patients, at the end of the study. The commonly observed adverse effects were nausea, vomiting, hair loss, fatigue, and tinnitus.
Conclusion: The studies have shown hearing loss in higher frequencies, but in our study, we have observed hearing loss at speech frequency in 22.2% of patients receiving cisplatin, who also had low serum albumin levels. Periodic audiometric monitoring and serum albumin level may be helpful to provide timely intervention to prevent further hearing loss and deterioration in the quality of life.

PMID: 30197356 [PubMed - indexed for MEDLINE]

Unintended Consequences of Systemic and Ablative Oncologic Therapy in the Abdomen and Pelvis.

Radiographics. 2018 Jul-Aug;38(4):1158-1179

Authors: Birch JC, Khatri G, Watumull LM, Arriaga YE, Leyendecker JR

Abstract
Human cancers are genetically complex and diverse. Although advances in oncologic therapy aim to define and target unique steps in carcinogenesis, oncologists often rely on less discriminate anticancer therapies that have consequences for normal tissues. Even many of the so-called targeted therapies currently employed can adversely affect normal cells, leading to complications that necessitate dose reductions or cessation of specific therapies. This article explores the unintended consequences of currently employed systemic and ablative anticancer therapies that might manifest at imaging examinations of the abdomen and pelvis, including cytotoxic, molecular targeted, and immunologic agents; ablation; and hematopoietic stem cell transplant. Each of these treatments can have both major and minor unintended effects in the targeted organ(s), in local or adjacent structures, or at distant sites. Timely detection and reporting of adverse consequences of anticancer therapies by the astute imager can result in critical treatment modifications and/or lifesaving interventions; therefore, knowledge of these unintended effects is paramount for radiologists interpreting the results of imaging examinations in cancer patients. ©RSNA, 2018.

PMID: 29995613 [PubMed - indexed for MEDLINE]

Local Radiotherapy Affects Drug Pharmacokinetics-Exploration of a Neglected but Significant Uncertainty of Cancer Therapy.

Technol Cancer Res Treat. 2017 12;16(6):705-716

Authors: Chen YJ, Tsai TH, Wang LY, Hsieh CH

Abstract
PURPOSE: Concurrent chemoradiation therapy is the mainstay of treatment for many types of malignancies. However, concurrent chemoradiation therapy is associated with a greater number of systemic adverse effects than radiotherapy or chemotherapy alone.
SUMMARY: Pharmacokinetics is the study of a drug and/or its metabolite kinetics in the body, including absorption, distribution, metabolism, and elimination. The incidences of adverse effects are markedly higher in patients who receive concurrent chemoradiation therapy than in those who receive either radiotherapy or chemotherapy alone. This phenomenon implies that irradiation affects the pharmacokinetics of cytotoxic agents, namely the radiotherapy-pharmacokinetic phenomenon. Experimental animal studies have shown that local irradiation affects the systemic pharmacokinetics of 5-fluorouracil and cisplatin at both low dose (simulating generous dose distributed to normal tissues) and daily practice dose (mimicking therapeutic dose to target volumes). These effects are significant in the circulation of blood and lymphatic system as well as in the hepatobiliary excretion. Furthermore, recent studies have demonstrated that matrix metalloproteinase-8 plays an important role in the radiotherapy-pharmacokinetic phenomenon.
CONCLUSION: In the present review, we provide a general overview of the radiotherapy-pharmacokinetic phenomenon and discuss the possible mechanisms governing the phenomenon.

PMID: 29332468 [PubMed - indexed for MEDLINE]

Neuropsychiatric adverse drug reactions in children initiated on montelukast in real-life practice.

Eur Respir J. 2017 11;50(5):

Authors: Ducharme FM, Bénard B

PMID: 29167307 [PubMed - indexed for MEDLINE]

Neuropsychiatric adverse drug reactions in children initiated on montelukast in real-life practice.

Eur Respir J. 2017 11;50(5):

Authors: Urdaneta E

PMID: 29167306 [PubMed - indexed for MEDLINE]

3,4-Methylenedioxymethamphetamine-assisted psychotherapy for treatment of chronic posttraumatic stress disorder: A randomized phase 2 controlled trial.

J Psychopharmacol. 2018 Oct 29;:269881118806297

Authors: Ot'alora G M, Grigsby J, Poulter B, Van Derveer JW, Giron SG, Jerome L, Feduccia AA, Hamilton S, Yazar-Klosinski B, Emerson A, Mithoefer MC, Doblin R

Abstract
BACKGROUND:: Posttraumatic stress disorder often does not resolve after conventional psychotherapies or pharmacotherapies. Pilot studies have reported that 3,4-methylenedioxymethamphetamine (MDMA) combined with psychotherapy reduces posttraumatic stress disorder symptoms.
AIMS:: This pilot dose response trial assessed efficacy and safety of MDMA-assisted psychotherapy across multiple therapy teams.
METHODS:: Twenty-eight people with chronic posttraumatic stress disorder were randomized in a double-blind dose response comparison of two active doses (100 and 125 mg) with a low dose (40 mg) of MDMA administered during eight-hour psychotherapy sessions. Change in the Clinician-Administered PTSD Scale total scores one month after two sessions of MDMA served as the primary outcome. Active dose groups had one additional open-label session; the low dose group crossed over for three open-label active dose sessions. A 12-month follow-up assessment occurred after the final MDMA session.
RESULTS:: In the intent-to-treat set, the active groups had the largest reduction in Clinician-Administered PTSD Scale total scores at the primary endpoint, with mean (standard deviation) changes of -26.3 (29.5) for 125 mg, -24.4 (24.2) for 100 mg, and -11.5 (21.2) for 40 mg, though statistical significance was reached only in the per protocol set ( p=0.03). Posttraumatic stress disorder symptoms remained lower than baseline at 12-month follow-up ( p<0.001) with 76% ( n=25) not meeting posttraumatic stress disorder criteria. There were no drug-related serious adverse events, and the treatment was well-tolerated.
CONCLUSIONS:: Our findings support previous investigations of MDMA-assisted psychotherapy as an innovative, efficacious treatment for posttraumatic stress disorder.

PMID: 30371148 [PubMed - as supplied by publisher]

3D-QSAR and Molecular Docking Studies on Design Anti-prostate Cancer Curcumin Analogues.

Curr Comput Aided Drug Des. 2018 Oct 29;:

Authors: Meng X, Cui L, Song F, Luan M, Ji J, Si H, Duan Y, Zhai H

Abstract
BACKGROUND: Prostate cancer is one of the most common tumors in the world and the fifth leading cause of male cancer death. Although successful in the treatment of localized androgen-dependent prostate cancer, the efficacy of androgen-independent metastatic disease is limited. Curcumin, a natural product, has been found to inhibit the proliferation of prostate cancer cells.
OBJECTIVE: In order to design curcumin analogues with higher biological activity and lower toxic and side effects for the treatment of prostate cancer.
METHODS: In this study, the three dimensional-quantitative structure activity relationship (3D-QSAR) and molecular docking studies were performed on 34 curcumin analogues as anti-prostate cancer compounds. And we introduced OSIRIS Property Explorer to predict drug-related properties of newly designed compounds.
RESULTS: The optimum CoMSIA model exhibited statistically significant results: the cross-validated correlation coefficient q2 is 0.540 and non-cross-validated R2 value is 0.984. The external predictive correlation coefficient is 0.792. The information of structure-activity relationship can obtain from the CoMSIA contour maps. In addition, the molecular docking study of the compounds for 3ZK6 as the protein target revealed important interactions between active compounds and amino acids.
CONCLUSION: Compound 28i may be a new type of anti-prostate cancer drug with higher biological activity and more promising development.

PMID: 30370853 [PubMed - as supplied by publisher]