PURPOSE: To provide recommendations for appropriate dosing of systemic antineoplastic agents in obese adults with cancer. METHODS: A systematic review of the literature collected evidence regarding dosing of chemotherapy, immunotherapy, and targeted therapies in obese adults with cancer. PubMed and the Cochrane Library were searched for randomized controlled trials, meta-analyses, or cohort studies published from November 1, 2010, through March 27, 2020. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS: Sixty studies, primarily retrospective, were included in the review. Overall, the evidence supported previous findings that obese adult patients tolerate full, body-size–based dosing of chemotherapy as well as nonobese patients. Fewer studies have addressed the dosing of targeted therapies and immunotherapies in relation to safety and efficacy in obese patients. RECOMMENDATIONS: The Panel continues to recommend that full, weight-based cytotoxic chemotherapy doses be used to treat obese adults with cancer. New to this version of the guideline, the Panel also recommends that full, approved doses of immunotherapy and targeted therapies be offered to obese adults with cancer. In the event of toxicity, the consensus of the Panel is that dose modifications of systemic antineoplastic therapies should be handled similarly for obese and nonobese patients. Important areas for future research include the impact of sarcopenia and other measures of body composition on optimal antineoplastic dosing, and more customized dosing based on pharmacokinetic or pharmacogenetic factors. Additional information is available at www.asco.org/supportive-care-guidelines .
Background Sepsis remains the top cause of morbidity and mortality of hospitalised patients despite concerted efforts. Clinical decision support for sepsis has shown mixed results reflecting heterogeneous populations, methodologies and interventions. Objectives To determine whether the addition of a real-time electronic health record (EHR)-based clinical decision support alert improves adherence to treatment guidelines and clinical outcomes in hospitalised patients with suspected severe sepsis. Design Patient-level randomisation, single blinded. Setting Medical and surgical inpatient units of an academic, tertiary care medical centre. Patients 1123 adults over the age of 18 admitted to inpatient wards (intensive care units (ICU) excluded) at an academic teaching hospital between November 2014 and March 2015. Interventions Patients were randomised to either usual care or the addition of an EHR-generated alert in response to a set of modified severe sepsis criteria that included vital signs, laboratory values and physician orders. Measurements and main results There was no significant difference between the intervention and control groups in primary outcome of the percentage of patients with new antibiotic orders at 3 hours after the alert (35% vs 37%, p=0.53). There was no difference in secondary outcomes of in-hospital mortality at 30 days, length of stay greater than 72 hours, rate of transfer to ICU within 48 hours of alert, or proportion of patients receiving at least 30 mL/kg of intravenous fluids. Conclusions An EHR-based severe sepsis alert did not result in a statistically significant improvement in several sepsis treatment performance measures.
PURPOSE: Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. METHODS: This retrospective study included PWH treated with anti–PD-1- or anti–PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC). RESULTS: Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti–PD-1/anti–PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load <400 copies/mL. Twenty percent (79/390) had any grade immune-related adverse events (irAEs) and 7.7% (30/390) had grade ≥3 irAEs. ORRs were 69% (nonmelanoma skin cancer), 31% (NSCLC), 16% (HCC), and 11% (HNSCC). In the matched mNSCLC cohort (61 PWH v 110 PWOH), 20% (12/61) PWH and 22% (24/110) PWOH had irAEs. Adjusted 42-month RMST difference was –0.06 months (95% CI, –5.49 to 5.37; P = .98) for PFS and 2.23 months (95% CI, –4.02 to 8.48; P = .48) for OS. CONCLUSION: Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.
1 July 2019 in Journal of Pain and Symptom Management