Purpose To update the ASCO guideline for antiemetics in oncology. Methods ASCO convened an Expert Panel and conducted a systematic review of the medical literature for the period of November 2009 to ...June 2016. Results Forty-one publications were included in this systematic review. A phase III randomized controlled trial demonstrated that adding olanzapine to antiemetic prophylaxis reduces the likelihood of nausea among adult patients who are treated with high emetic risk antineoplastic agents. Randomized controlled trials also support an expanded role for neurokinin 1 receptor antagonists in patients who are treated with chemotherapy. Recommendation Key updates include the addition of olanzapine to antiemetic regimens for adults who receive high-emetic-risk antineoplastic agents or who experience breakthrough nausea and vomiting; a recommendation to administer dexamethasone on day 1 only for adults who receive anthracycline and cyclophosphamide chemotherapy; and the addition of a neurokinin 1 receptor antagonist for adults who receive carboplatin area under the curve ≥ 4 mg/mL per minute or high-dose chemotherapy, and for pediatric patients who receive high-emetic-risk antineoplastic agents. For radiation-induced nausea and vomiting, adjustments were made to anatomic regions, risk levels, and antiemetic administration schedules. Rescue therapy alone is now recommended for low-emetic-risk radiation therapy. The Expert Panel reiterated the importance of using the most effective antiemetic regimens that are appropriate for antineoplastic agents or radiotherapy being administered. Such regimens should be used with initial treatment, rather than first assessing the patient's emetic response with less-effective treatment. Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki .
Antiemetics: ASCO Guideline Update Hesketh, Paul J; Kris, Mark G; Basch, Ethan ...
Journal of clinical oncology,
08/2020, Letnik:
38, Številka:
24
Journal Article
Recenzirano
To update the guideline to include new anticancer agents, antiemetics, and antiemetic regimens and to provide recommendations on the use of dexamethasone as a prophylactic antiemetic in patients ...receiving checkpoint inhibitors (CPIs).
ASCO convened an Expert Panel and updated the systematic review to include randomized controlled trials (RCTs) and meta-analyses of RCTs published between June 1, 2016, and January 24, 2020. To address the dexamethasone and CPI question, we conducted a systematic review of RCTs that evaluated the addition of a CPI to chemotherapy.
The systematic reviews included 3 publications from the updated search and 10 publications on CPIs. Two phase III trials in adult patients with non-small-cell lung cancers evaluating a platinum-based doublet with or without the programmed death 1 (PD-1) inhibitor pembrolizumab recommended that all patients receive dexamethasone as a component of the prophylactic antiemetic regimen. In both studies, superior outcomes were noted in the PD-1 inhibitor-containing arms. Other important findings address olanzapine in adults and fosaprepitant in pediatric patients.
Recommendations for adults are unchanged with the exception of the option of adding olanzapine in the setting of hematopoietic stem cell transplantation. Dosing information now includes the option of a 5-mg dose of olanzapine in adults and intravenous formulations of aprepitant and netupitant-palonosetron. The option of fosaprepitant is added to pediatric recommendations. There is no clinical evidence to warrant omission of dexamethasone from guideline-compliant prophylactic antiemetic regimens when CPIs are administered to adults in combination with chemotherapy. CPIs administered alone or in combination with another CPI do not require the routine use of a prophylactic antiemetic.Additional information is available at www.asco.org/supportive-care-guidelines.
We studied the use of palliative radiotherapy (RT) among patients with primary, non-curable, locally advanced pancreatic cancer. In this subset of patients, with very poor survival, various ...palliative RT dose fractionation schemes are used; but, in the absence of a guideline, practice patterns vary, and dose choice is mainly based on the physician's intuition. We divided the patients into three groups, according to the dose fractionation schedules received: low (A), intermediate (B), and high (C) dose groups, to study the potential differences in outcome between the different dose prescriptions. Cohort:
= 184. Median age: 69 years. Male:
= 105 (57%), female:
= 79 (43%). Stage IV:
= 117 (64%). T4:
= 127 (69%). Tumor location: head:
= 109 (59%), body:
= 37 (20%), tail:
= 25 (14%), neck:
= 11 (6%), and uncinate:
= 2 (1%). Prior systemic therapy:
= 66 (36%). Most common dose fractionations received: 20 Gy in five fractions
= 67 (36%), 30 Gy in 10 fractions
= 49 (27%), and 8 Gy in one fraction
= 23 (13%). Group A:
= 33 (18%), median overall survival (OS) 19 days (95% CI 4-33). Group B:
= 84 (46%), median OS 52 days (95% CI 43-60). Group C:
= 67 (36%), median OS 126 days (95% CI 77-174). Median days to in-field progression: Group A 59 days (range 7-109), Group B 96 days (range 19-173), and Group C 97 days (range 13-475). To our knowledge, this is the largest reported retrospective cohort of patients receiving non-ablative palliative RT to treat their primary pancreatic tumors. Most patients had metastatic disease, T4 tumors of the pancreatic head and had not received prior systemic therapy. A significant survival benefit was seen favoring the high dose/longer RT fractionation group, presumably due to appropriate patient selection rather than an RT effect. Despite the relatively short median overall survival, one fifth of the patients were found to experience an in-field progression following RT.
We studied the dose-local control (LC) relationship in ablative vs. non-ablative radiotherapy in a non-radical treatment setting of "locally advanced pancreatic cancer (LAPC)" by comparing our ...patients (n = 89) treated with SBRT on the CyberKnife unit vs. conventional radiation between January 2005 and January 2021, and by reviewing the literature. A systematic search was performed leveraging Medline for references on SBRT use in pancreatic cancer without date terms or language restrictions. A total of 3702 references were identified and the search was then repeated in Embase and the Cochrane database. Ultimately, 12 studies were eligible for inclusion, which either compared SBRT to conventional radiation, or SBRT use in dose escalation for primary LAPC in a non-neoadjuvant setting. Our cohort's median overall survival was 152 days (CI 95%, 118-185); including 371 days (CI 95%, 230-511) vs. 126 days (CI 95%, 90-161) favoring SBRT,
= 0.004. The median time to local progression was 170 days (48-923) for SBRT vs. 107 days (27-489) for the non-ablative group. In our SBRT patients, no local progressions were seen with BED
> 60 Gy. Even when palliating LAPC, SBRT should be considered as an alternative to conventional radiation, especially in patients with a low disease burden. BED
≥ 60-70 Gy offers better local control without increasing toxicity rates. Less local progression may provide a better quality of life to those patients who already have a short life expectancy.
Metastasis is the most common cause of death of prostate cancer patients. Identification of specific metastasis biomarkers and novel therapeutic targets is considered essential for improved prognosis ...and management of the disease. MicroRNAs (miRNAs) form a class of non-coding small RNA molecules considered to be key regulators of gene expression. Their dysregulation has been shown to play a role in cancer onset, progression and metastasis, and miRNAs represent a promising new class of cancer biomarkers. The objective of this study was to identify down- and up-regulated miRNAs in prostate cancer that could provide potential biomarkers and/or therapeutic targets for prostate cancer metastasis.
Next generation sequencing technology was applied to identify differentially expressed miRNAs in a transplantable metastatic versus a non-metastatic prostate cancer xenograft line, both derived from one patient's primary cancer. The xenografts were developed via subrenal capsule grafting of cancer tissue into NOD/SCID mice, a methodology that tends to preserve properties of the original cancers (e.g., tumor heterogeneity, genetic profiles).
Differentially expressed known miRNAs, isomiRs and 36 novel miRNAs were identified. A number of these miRNAs (21/104) have previously been reported to show similar down- or up-regulation in prostate cancers relative to normal prostate tissue, and some of them (e.g., miR-16, miR-34a, miR-126*, miR-145, miR-205) have been linked to prostate cancer metastasis, supporting the validity of the analytical approach.
The use of metastatic and non-metastatic prostate cancer subrenal capsule xenografts derived from one patient's cancer makes it likely that the differentially expressed miRNAs identified in this study include potential biomarkers and/or therapeutic targets for human prostate cancer metastasis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background Pain flare occurs after palliative radiotherapy, and dexamethasone has shown potential for prevention of such flare. We aimed to compare the efficacy of dexamethasone with that of ...placebo in terms of reduction of incidence of pain flare. Methods In this double-blind, randomised, placebo-controlled phase 3 trial, patients from 23 Canadian centres were randomly allocated (1:1) with a web-based system and minimisation algorithm to receive either two 4 mg dexamethasone tablets or two placebo tablets taken orally at least 1 h before the start of radiation treatment (a single 8 Gy dose to bone metastases; day 0) and then every day for 4 days after radiotherapy (days 1–4). Patients were eligible if they had a non-haematological malignancy and bone metastasis (or metastases) corresponding to the clinically painful area or areas. Patients reported their worst pain scores and opioid analgesic intake before treatment and daily for 10 days after radiation treatment. They completed the European Organisation for Research and Treatment of Cancer (EORTC) quality of life QLQ-C15-PAL, the bone metastases module (EORTC QLQ-BM22), and the Dexamethasone Symptom Questionnaire at baseline, and at days 10 and 42 after radiation treatment. Pain flare was defined as at least a two-point increase on a scale of 0–10 in the worst pain score with no decrease in analgesic intake, or a 25% or greater increase in analgesic intake with no decrease in the worst pain score from days 0–10, followed by a return to baseline levels or below. Primary analysis of incidence of pain flare was by intention-to-treat (patients with missing primary data were classified as having pain flare). This study is registered with ClinicalTrials.gov , number NCT01248585 , and is completed. Findings Between May 30, 2011, and Dec 11, 2014, 298 patients were enrolled. 39 (26%) of 148 patients randomly allocated to the dexamethasone group and 53 (35%) of 150 patients in the placebo group had a pain flare (difference 8·9%, lower 95% confidence bound 0·0, one-sided p=0·05). Two grade 3 and one grade 4 biochemical hyperglycaemic events occurred in the dexamethasone group (without known clinical effects) compared with none in the placebo group. The most common adverse events were bone pain (61 41% of 147 vs 68 48% of 143), fatigue (58 39% of 147 vs 49 34% of 143), constipation (47 32% of 147 vs 37 26% of 143), and nausea (34 23% of 147 vs 34 24% of 143), most of which were mild grade 1 or 2. Interpretation Dexamethasone reduces radiation-induced pain flare in the treatment of painful bone metastases. Funding The NCIC CTG's programmatic grant from the Canadian Cancer Society Research Institute.
To review the published literature pertaining to radiation oncology in undergraduate medical education.
Ovid MEDLINE, Ovid MEDLINE Daily Update and EMBASE databases were searched for the 11-year ...period of January 1, 1998, through the last week of March 2009. A medical librarian used an extensive list of indexed subject headings and text words.
The search returned 640 article references, but only seven contained significant information pertaining to teaching radiation oncology to medical undergraduates. One article described a comprehensive oncology curriculum including recommended radiation oncology teaching objectives and sample student evaluations, two described integrating radiation oncology teaching into a radiology rotation, two described multidisciplinary anatomy-based courses intended to reinforce principles of tumor biology and radiotherapy planning, one described an exercise designed to test clinical reasoning skills within radiation oncology cases, and one described a Web-based curriculum involving oncologic physics.
To the authors' knowledge, this is the first review of the literature pertaining to teaching radiation oncology to medical undergraduates, and it demonstrates the paucity of published work in this area of medical education. Teaching radiation oncology should begin early in the undergraduate process, should be mandatory for all students, and should impart knowledge relevant to future general practitioners rather than detailed information relevant only to oncologists. Educators should make use of available model curricula and should integrate radiation oncology teaching into existing curricula or construct stand-alone oncology rotations where the principles of radiation oncology can be conveyed. Assessments of student knowledge and curriculum effectiveness are critical.
Purpose
The aim of this project was to develop clinical practice guidelines on the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and management of oral ...mucositis (OM) in cancer patients.
Methods
A systematic review of the available literature was conducted. The body of evidence for the use of each agent, in each setting, was assigned a level of evidence. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, or no guideline possible.
Results
A recommendation was developed in favor of patient-controlled analgesia with morphine in hematopoietic stem cell transplant (HSCT) patients. Suggestions were developed in favor of transdermal fentanyl in standard dose chemotherapy and HSCT patients and morphine mouth rinse and doxepin rinse in head and neck radiation therapy (H&N RT) patients. Recommendations were developed against the use of topical antimicrobial agents for the prevention of mucositis. These included recommendations against the use of iseganan for mucositis prevention in HSCT and H&N RT and against the use of antimicrobial lozenges (polymyxin–tobramycin–amphotericin B lozenges/paste and bacitracin–clotrimazole–gentamicin lozenges) for mucositis prevention in H&N RT. Recommendations were developed against the use of the mucosal coating agent sucralfate for the prevention or treatment of chemotherapy-induced or radiation-induced OM. No guidelines were possible for any other agent due to insufficient and/or conflicting evidence.
Conclusion
Additional well-designed research is needed on prevention and management approaches for OM.
Patients with metastatic epidural spinal cord compression (MESCC) and favorable survival prognoses may benefit from radiation doses exceeding 10 × 3.0 Gy. In a multi-center phase 2 trial, patients ...receiving 15 × 2.633 Gy (41.6 Gy
) or 18 × 2.333 Gy (43.2 Gy
) were evaluated for local progression-free survival (LPFS), motor/sensory functions, ambulatory status, pain, distress, toxicity, and overall survival (OS). They were compared (propensity score-adjusted Cox regression) to a historical control group (n = 266) receiving 10 × 3.0 Gy (32.5 Gy
). In the phase 2 cohort, 50 (of 62 planned) patients were evaluated for LPFS. Twelve-month rates of LPFS and OS were 96.8% and 69.9%, respectively. Motor and sensory functions improved in 56% and 57.1% of patients, and 94.0% were ambulatory following radiotherapy. Pain and distress decreased in 84.4% and 78.0% of patients. Ten and two patients experienced grade 2 and 3 toxicities, respectively. Phase 2 patients showed significantly better LPFS than the control group (
= 0.039) and a trend for improved motor function (
= 0.057). Ambulatory and OS rates were not significantly different. Radiotherapy with 15 × 2.633 Gy or 18 × 2.333 Gy was well tolerated and appeared superior to 10 × 3.0 Gy.
To systematically review the effectiveness and safety of 5-hydroxytryptamine-3 receptor antagonists (5-HT3 RAs) compared with other antiemetic medication or placebo for prophylaxis of ...radiation-induced nausea and vomiting.
We searched the following electronic databases: MEDLINE, Embase, the Cochrane Central Register of Controlled Clinical Trials, and Web of Science. We also hand-searched reference lists of included studies. Randomized, controlled trials that compared a 5-HT3 RA with another antiemetic medication or placebo for preventing radiation-induced nausea and vomiting were included. We excluded studies recruiting patients receiving concomitant chemotherapy. When appropriate, meta-analysis was conducted using Review Manager (v5) software. Relative risks were calculated using inverse variance as the statistical method under a random-effects model. We assessed the quality of evidence by outcome using the Grading of Recommendations Assessment, Development, and Evaluation approach.
Eligibility screening of 47 articles resulted in 9 included in the review. The overall methodologic quality was moderate. Meta-analysis of 5-HT3 RAs vs. placebo showed significant benefit for 5-HT3 RAs (relative risk RR 0.70; 95% confidence interval CI 0.57-0.86 for emesis; RR 0.84, 95% CI 0.73-0.96 for nausea). Meta-analysis comparing 5-HT3 RAs vs. metoclopramide showed a significant benefit of the 5-HT3 RAs for emetic control (RR 0.27, 95% CI 0.15-0.47).
5-Hydroxytryptamine-3 RAs are superior to placebo and other antiemetics for prevention of emesis, but little benefit was identified for nausea prevention. 5-Hydroxytryptamine-3 RAs are suggested for prevention of emesis. Limited evidence was found regarding delayed emesis, adverse events, quality of life, or need for rescue medication. Future randomized, controlled trials should evaluate different 5-HT3 antiemetics and new agents with novel mechanisms of action such at the NK(1) receptor antagonists to determine the most effective drug. Delayed nausea and vomiting should be a focus of future study, perhaps concentrating on the palliative cancer population.
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