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Mucositis reduction with probiotics in children with cancer: a randomised-controlled feasibility study.
Hassan, H, Kinsey, S, Phillips, B
Archives of disease in childhood. 2022;(3):259-264
Abstract
BACKGROUND A recent systematic review and meta-analysis identified a paucity of randomised-controlled trials (RCTs) investigating the use of probiotics to reduce or prevent mucositis and infection in children with cancer. OBJECTIVE This study evaluated the feasibility of undertaking an RCT and investigated the efficacy of probiotics for reducing or preventing mucositis and infection in children with cancers. SETTING The Paediatric Oncology and Haematology department at Leeds Teaching Hospital, UK. PATIENTS Children aged 1 year or older, receiving chemotherapies likely to cause mucositis. INTERVENTIONS Participants were randomised to receive the probiotic or placebo on day 1-14 of a chemotherapy cycle. Participants were also required to complete a patient diary for 21 days. MAIN OUTCOME MEASURES To assess whether it is feasible to recruit children diagnosed with cancer who are at risk of developing mucositis to an adequately powered RCT. RESULTS Between May and November 2019, 34 out of 39 eligible participants were approached. Ten patients were recruited (4 probiotic and 6 placebo) of which 2 participants withdrew. Seven participants partially completed the diary but only two participants completed 80% or more. Eligible participants appeared to prefer giving informal verbal feedback when in direct contact with research and healthcare professionals. CONCLUSION This study demonstrated that recruitment needs to be improved prior to undertaking an adequately powered RCT. TRIAL REGISTRATION NUMBER NCT03785938.
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Effect of Food on the Pharmacokinetics of the Oral Docetaxel Tablet Formulation ModraDoc006 Combined with Ritonavir (ModraDoc006/r) in Patients with Advanced Solid Tumours.
Vermunt, MAC, de Weger, VA, Janssen, JM, Lopez-Yurda, MI, Keessen, M, Thijssen, B, Rosing, H, Huitema, ADR, Beijnen, JH, Marchetti, S
Drugs in R&D. 2021;(1):103-111
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INTRODUCTION ModraDoc006 is a novel docetaxel tablet formulation that is co-administrated with the cytochrome P450 3A4 and P-glycoprotein inhibitor ritonavir (r): ModraDoc006/r. OBJECTIVES This study evaluated the effect of food consumed prior to administration of ModraDoc006/r on the pharmacokinetics of docetaxel and ritonavir. METHODS Patients with advanced solid tumours were enrolled in this randomized crossover study to receive ModraDoc006/r in a fasted state in week 1 and after a standardized high-fat meal in week 2 and vice versa. Pharmacokinetic sampling was conducted until 48 h after both study drug administrations. Docetaxel and ritonavir plasma concentrations were determined using liquid chromatography with tandem mass spectrometry. Safety was evaluated with the Common Terminology Criteria for Adverse Events, version 4.03. RESULTS In total, 16 patients completed the food-effect study. The geometric mean ratio (GMR) for the docetaxel area under the plasma concentration-time curve (AUC)0-48, AUC0-inf and maximum concentration (Cmax) were 1.11 (90% confidence interval [CI] 0.93-1.33), 1.19 (90% CI 1.00-1.41) and 1.07 (90% CI 0.81-1.42) in fed versus fasted conditions, respectively. For the ritonavir Cmax, the GMR was 0.79 (90% CI 0.69-0.90), whereas the AUC0-48 and AUC0-inf were bioequivalent. The most frequent treatment-related toxicities were grade ≤ 2 diarrhoea and fatigue. Hypokalaemia was the only observed treatment-related grade 3 toxicity. CONCLUSIONS The docetaxel and ritonavir exposure were not bioequivalent, as consumption of a high-fat meal prior to administration of ModraDoc006/r resulted in a slightly higher docetaxel exposure and lower ritonavir Cmax. Since docetaxel exposure is the only clinically relevant parameter in our patient population, the overall conclusion is that combined ModraDoc006 and ritonavir treatment may be slightly affected by concomitant intake of a high-fat meal. In view of the small effect, it is most likely that the intake of a light meal will not affect the systemic exposure to docetaxel. CLINICALTRIALS. GOV IDENTIFIER NCT03147378, date of registration: May 10 2017.
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Vitamin D Supplementation for Prevention of Cancer: The D2d Cancer Outcomes (D2dCA) Ancillary Study.
Chatterjee, R, Fuss, P, Vickery, EM, LeBlanc, ES, Sheehan, PR, Lewis, MR, Dolor, RJ, Johnson, KC, Kashyap, SR, Nelson, J, et al
The Journal of clinical endocrinology and metabolism. 2021;(9):2767-2778
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CONTEXT Observational studies suggest that low vitamin D status may be a risk factor for cancer. OBJECTIVE In a population with prediabetes and overweight/obesity that is at higher risk of cancer than the general population, we sought to determine if vitamin D supplementation lowers the risk of cancer and precancers. METHODS The Vitamin D and type 2 diabetes (D2d) cancer outcomes study (D2dCA) is an ancillary study to the D2d study, which was conducted at 22 academic medical centers in the United States. Participants had prediabetes and overweight/obesity and were free of cancer for the previous 5 years. Participants were randomized to receive vitamin D3 4000 IU daily or placebo. At scheduled study visits (4 times/year), cancer and precancer events were identified by questionnaires. Clinical data were collected and adjudicated for all reported events. Cox proportional hazard models compared the hazard ratio (HR) of incident cancers and precancers between groups. RESULTS Over a median follow-up period of 2.9 years, among 2385 participants (mean age 60 years and 25-hydroxyvitamin D 28 ng/mL), there were 89 cases of cancer. The HR of incident cancer for vitamin D vs placebo was 1.07 (95% CI 0.70, 1.62). Of 241 participants with incident precancers, 239 had colorectal adenomatous polyps. The HR for colorectal polyps for vitamin D vs placebo was 0.83 (95% CI 0.64, 1.07). CONCLUSION In the D2d population of participants with prediabetes and overweight/obesity, not selected for vitamin D insufficiency, vitamin D supplementation did not have a significant effect on risk of incident cancer or colorectal polyps.
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Efficacy and safety of oral magnesium supplementation in reducing febrile neutropenia episodes in children with solid tumors treated with cisplatin-based chemotherapy: randomized clinical trial.
Castelán-Martínez, OD, Palomo-Colli, MA, Barrios-López, VE, Silva-Jivaja, KM, Juárez-Villegas, LE, Castañeda-Hernández, G, Sánchez-Rodríguez, MA
Cancer chemotherapy and pharmacology. 2020;(5):673-679
Abstract
PURPOSE Hypomagnesemia has been associated with febrile neutropenia (FN) in pediatric patients receiving cisplatin-based chemotherapy (CDDPBC). The primary aim was to determine whether oral magnesium supplementation reduces FN episodes in pediatric patients with solid tumors treated with CDDPBC. METHOD This randomized clinical trial, with open-label, single-center, parallel group and superiority design was conducted in Hospital Infantil de Mexico Federico Gomez at Mexico City. Children ≥ 9 years with solid tumors that were to receive a CDDPBC cycle were invited to participate. Each chemotherapy cycle with CDDPBC was randomly assigned to receive oral magnesium supplementation (250 mg/day) or not receive magnesium supplementation (control group). Efficacy was determined by relative risks (RR) with 95% confidence intervals (95% CI) as well as with numbers needed to treat (NNT). Active surveillance was conducted to assess safety in both groups. Analyses were carried out by intention to treat. ClinicalTrials.gov number NCT03449693. RESULTS One hundred and one chemotherapy cycles with CDDPBC were analyzed (50 in the magnesium supplement arm and 51 in control group). Baseline clinical characteristics were similar comparing both groups. Oral magnesium supplementation reduces FN episodes compared to control group [RR 0.53, (95% CI 0.32-0.89), NNT = 4]. In the supplemented group, patients had fewer episodes of septic shock secondary to FN [RR 0.43, (95% CI 0.02-0.94), NNT = 6] and FN appeared on average 5 days later (p = 0.031). Hypomagnesemia episodes and adverse events were similar across both groups. CONCLUSION Oral supplementation with magnesium reduces FN episodes neutropenia in pediatric patients with solid tumors treated with CDDPBC.
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Topical Costus sp. Preparation as Palliative Care for Chemotherapy-Induced Peripheral Neuropathy of Patients: A Randomized Placebo-Controlled Pilot Trial.
Heydarirad, G, Cramer, H, Choopani, R, Gharehgozlou, R, Mosavat, SH, Ameri, A, Pasalar, M
Journal of alternative and complementary medicine (New York, N.Y.). 2020;(9):807-812
Abstract
Objectives: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of various anticancer regimens with different sensory-motor abnormalities in patients. The aim of this study was to examine the feasibility of using Costus sp. oil as a palliative treatment in such patients. Design: This was a pilot randomized placebo-controlled double-blind clinical study. Settings/Location: Imam Hossein Hospital, Tehran, Iran. Subjects: Patients 18-80 years of age undergoing chemotherapy treatment recently or during the last 6 months were enrolled after meeting the inclusion criteria. Interventions: The intervention group used Costus sp. as a topical ointment and the placebo group used topical paraffin for 4 weeks. Outcome measures: Feasibility of recruitment, including treatment acceptability (evaluated as number of patients leaving the study early), and compliance (defined as consumption of a minimum 80% of the ointment) with the intervention were assessed. Neuropathic pain change was defined as the secondary outcome, too. Results: Totally, 50 out of 73 participants were identified eligible and were randomly divided into intervention or placebo groups. There was no significant difference between groups in terms of sociodemographic data. At the end of the study, 24% (confidence interval [95% CI]: 9-45) (intervention group) and 12% (95% CI: 2-31) (placebo group) of patients revealed treatment unacceptability. Meanwhile, 12% (95% CI: 2-31) in the intervention group and 28% (95% CI: 12-49) in the placebo group did not show the compliance. Moreover, according to patients' records, pain reduction was higher in the intervention group compared to the placebo group (p = 0.001). Conclusions: This preliminary study showed that topical use of Costus sp. was feasible and acceptable in patients suffering from CIPN.
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Efficacy of Improvised Topical Zinc (1%) Ora-Base on Oral Mucositis during Cancer Chemo-Radiation-A Randomized Study.
Chaitanya, N, Badam, R, Aryasri, AS, Pallarla, S, Garlpati, K, Akhila, M, Soni, P, Gali, S, Inamdar, P, Parinita, B, et al
Journal of nutritional science and vitaminology. 2020;(2):93-97
Abstract
Oral mucositis refers to erythematous and ulcerative lesions of oral mucosa during chemo/radiotherapy. Treatment modalities were directed towards reduction in severity of oral mucositis. Zinc plays an important role to retard oxidative processes and is considered as the critical component in wound healing. To compare the efficacy of zinc alone with improvised zinc preparation in reducing the severity of oral mucositis. Improvised zinc was a combination of zinc oxide, amla, tulsi and curcumin at 1% therapeutic concentrations. Seventy-five subjects undergoing chemo/radiotherapy were randomly divided into three groups: Group A (25 subjects) had received topical 5% zinc oxide paste trice daily application after food for entire treatment period, initiated 2 d prior to radiotherapy. Group B (25) received improvised zinc preparations (1%) and instructed to apply same as group A. Group C (25) received standard treatment offered by cancer hospital. All the groups were assessed for oral mucositis using WHO grading system at 7th, 14th, 21st, 28th, 35th day by the oncologist and results were tabulated for statistical analysis. Severity of oral mucositis reduced in zinc and improvised zinc group (p=0.096) when compared with controls with significant p value (0.037). Comparison of improvised zinc preparation (1%) group with only zinc group revealed that severity of overall mucositis though was not significant, was less in improvised zinc group with p value (0.029, 0.013) at 28 and 35 d respectively. Improvised zinc administration during radiation therapy was beneficial in reduction of oral mucositis during cancer treatment.
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Intensive Weight Loss Intervention and Cancer Risk in Adults with Type 2 Diabetes: Analysis of the Look AHEAD Randomized Clinical Trial.
, , Yeh, HC, Bantle, JP, Cassidy-Begay, M, Blackburn, G, Bray, GA, Byers, T, Clark, JM, Coday, M, Egan, C, et al
Obesity (Silver Spring, Md.). 2020;(9):1678-1686
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OBJECTIVE This study was designed to determine whether intensive lifestyle intervention (ILI) aimed at weight loss lowers cancer incidence and mortality. METHODS Data from the Look AHEAD trial were examined to investigate whether participants randomized to ILI designed for weight loss would have reduced overall cancer incidence, obesity-related cancer incidence, and cancer mortality, as compared with the diabetes support and education (DSE) comparison group. This analysis included 4,859 participants without a cancer diagnosis at baseline except for nonmelanoma skin cancer. RESULTS After a median follow-up of 11 years, 684 participants (332 in ILI and 352 in DSE) were diagnosed with cancer. The incidence rates of obesity-related cancers were 6.1 and 7.3 per 1,000 person-years in ILI and DSE, respectively, with a hazard ratio (HR) of 0.84 (95% CI: 0.68-1.04). There was no significant difference between the two groups in total cancer incidence (HR, 0.93; 95% CI: 0.80-1.08), incidence of nonobesity-related cancers (HR, 1.02; 95% CI: 0.83-1.27), or total cancer mortality (HR, 0.92; 95% CI: 0.68-1.25). CONCLUSIONS An ILI aimed at weight loss lowered incidence of obesity-related cancers by 16% in adults with overweight or obesity and type 2 diabetes. The study sample size likely lacked power to determine effect sizes of this magnitude and smaller.
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Effect of food on the pharmacokinetics of the WEE1 inhibitor adavosertib (AZD1775) in patients with advanced solid tumors.
Någård, M, Ah-See, ML, So, K, Vermunt, M, Thistlethwaite, F, Labots, M, Roxburgh, P, Ravaud, A, Campone, M, Valkenburg-van Iersel, L, et al
Cancer chemotherapy and pharmacology. 2020;(1):97-108
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PURPOSE To support future dosing recommendations, the effect of food on the pharmacokinetics of adavosertib, a first-in-class, small-molecule reversible inhibitor of WEE1 kinase, was assessed in patients with advanced solid tumors. METHODS In this Phase I, open-label, randomized, two-period, two-sequence crossover study, the pharmacokinetics of a single 300 mg adavosertib dose were investigated in fed versus fasted states. RESULTS Compared with the fasted state, a high-fat, high-calorie meal (fed state) decreased adavosertib maximum plasma concentration (Cmax) by 16% and systemic exposure (area under the plasma concentration-time curve [AUC]) by 6%; AUC0-t decreased by 7% and time to maximum plasma concentration was delayed by 1.97 h (P = 0.0009). The 90% confidence interval of the geometric least-squares mean treatment ratio for AUC and AUC0-t was contained within the no-effect limits (0.8-1.25), while that of Cmax crossed the lower bound of the no-effect limits. Adverse events (AEs) related to adavosertib treatment were reported by 20 (64.5%) of the 31 patients treated in this study. Grade ≥ 3 AEs were reported by four (12.9%) patients (one in the fed state, three in the fasted state); two of these AEs were considered treatment-related by the investigator. Three serious AEs were reported in three (9.7%) patients; these were not considered treatment-related. No patients discontinued because of treatment-related AEs, and no new safety signals were reported. CONCLUSION A high-fat meal did not have a clinically relevant effect on the systemic exposure of adavosertib, suggesting that adavosertib can be administered without regard to meals.
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Evaluation of an online knowledge translation intervention to promote cancer risk reduction behaviours: findings from a randomized controlled trial.
Neil-Sztramko, SE, Belita, E, Levinson, AJ, Boyko, J, Dobbins, M
BMC cancer. 2019;(1):1138
Abstract
BACKGROUND Many cancers are preventable through lifestyle modification; however, few adults engage in behaviors that are in line with cancer prevention guidelines. This may be partly due to the mixed messages on effective cancer prevention strategies in popular media. The goal of the McMaster Optimal Aging Portal (the Portal) is to increase access to trustworthy health information. The purpose of this study was to explore if and how knowledge translation strategies to disseminate cancer prevention evidence using the Portal influence participants' knowledge, intentions and health behaviors related to cancer risk. METHODS Adults ≥40 years old, with no cancer history were randomized to a 12-week intervention (weekly emails and social media posts) or control group. Quantitative data on knowledge, intentions and behaviors (physical activity, diet, alcohol consumption and use of tobacco products) were collected at baseline, end of study and 3 months later. Participant engagement was assessed using Google Analytics, and participant satisfaction through open-ended survey questions and semi-structured interviews. RESULTS Participants (n = 557, mean age 64.9) were predominantly retired (72%) females (81%). Knowledge of cancer prevention guidelines was higher in the intervention group at end of study only (+ 0.3, p = 0.01). Intentions to follow cancer prevention guidelines increased in both groups, with no between-group differences. Intervention participants reported greater light-intensity physical activity at end of study (+ 0.7 vs. 0.1, p = 0.03), and reduced alcohol intake at follow u (- 0.2 vs. + 0.3, p < 0.05), but no other between-group differences were found. Overall satisfaction with the Portal and intervention materials was high. CONCLUSIONS Dissemination of evidence-based cancer prevention information through the Portal results in small increases in knowledge of risk-reduction strategies and with little to no impact on self-reported health behaviours, except in particular groups. Further tailoring of knowledge translation strategies may be needed to see more meaningful change in knowledge and health behaviours. TRIAL REGISTRATION ClinicalTrials.gov NCT03186703, June 14, 2017.
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Effect of a mixed-exercise program on physical capacity and sedentary behavior in older adults during cancer treatments.
Maréchal, R, Fontvieille, A, Parent-Roberge, H, Fülöp, T, Riesco, E, Pavic, M, Dionne, IJ
Aging clinical and experimental research. 2019;(11):1583-1589
Abstract
BACKGROUND Aging, cancer and its treatment all contribute to increase the risk of deconditioning and sedentary behaviors. Mixed exercise is recognized to counteract the effects of aging and deconditioning as well as improving physical capacity during cancer treatment in adults. AIMS To determine the impact of a mixed exercise program (MXEP) to improve physical capacity and decrease sedentary behavior time (SBT) in older adults during cancer treatment. METHODS Fourteen participants (68.8 ± 3.4 years) completed 12 weeks of a mixed exercise program (MEXP) (n = 6) or stretching (n = 8) while they were under cancer treatment. Five tests of the Senior Fitness Test (Chair Stand, 8-Foot Up & Go, Arm Curl, Sit & Reach, 6 min Walk Test), two maximal strength tests (leg press and handgrip) and a Global Physical Capacity Score (GPCS) were used to assess physical capacity. For the amount of SBT (min/day), we used question 1 of the Physical Activity Scale for the Elderly. RESULTS Both groups presented significant pre- vs post-intervention differences for the Chair Stand, Arm Curl, 6 min Walk Tests and also GPCS. Nevertheless, this difference was significantly greater in the MEXP group only for the Chair Stand Test (4.3 ± 2.2 vs 1.0 ± 1.3 reps; p = 0.01) and the GPCS (4.0 ± 0.6 vs 1.5 ± 2.3 points; p = 0.047). A tend to display a greater decrease in SBT (- 295 ± 241 min/week vs - 11 ± 290 min/week; p = 0.079) was observed in favor of MEXP. CONCLUSION A 12-week mixed exercise program led to significant improvements in physical capacity and may reduce SBT.