Mark Pasetka

Prophylaxis of radiation-induced nausea and vomiting using 5-hydroxytryptamine-3 serotonin receptor antagonists: a systematic review of randomized trials.

PURPOSE 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. METHODS AND MATERIALS 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. RESULTS 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). CONCLUSION 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.

Update on the management of chemotherapy-induced nausea and vomiting – focus on palonosetron

Purpose Nausea and vomiting are major adverse effects of chemotherapy and can greatly impact patients’ quality of life. Although chemotherapy-induced nausea and vomiting (CINV) prevalence is high, treatment remains difficult. Palonosetron is a 5-hydroxytryptamine receptor antagonist (5-HT3RA) approved for treatment of CINV. The purpose of this review is to discuss existing and emerging therapeutic options, and examine studies focusing on palonosetron with regards to efficacy, pharmacology, tolerability, safety, and patient-derived outcomes. Methods A literature search was conducted using Ovid MEDLINE and EMBASE to identify relevant studies using palonosetron alone or in combination with other antiemetics. Studies were extracted if they included complete response (CR), complete control (CC), no nausea, no vomiting, and no rescue medications as an endpoint. Studies were also included if safety endpoints were examined. Results Palonosetron alone has been shown to improve CR and CC rates for patients receiving low, moderate, or high emetogenic chemotherapy. Rates were further improved with the addition of dexamethasone, a corticosteroid. Furthermore, the addition of neurokinin-1 receptor antagonists, such as netupitant markedly improved efficacy profiles compared to palonosetron alone. Aprepitant is an antiemetic that has exhibited positive results in combination with palonosetron. Recently, a new drug consisting of netupitant and palonosetron (NEPA) has demonstrated significantly more efficacious prevention of CINV. Regardless of the combination, palonosetron has been well tolerated. The most common adverse events were constipation, headache, fatigue, and dizziness, with the majority of patients describing them as only mild or moderate. Conclusion Palonosetron, alone or with other antiemetics, has improved CINV treatment due to its ability to significantly reduce delayed phases of CINV, compared to similar 5-HT3RAs. Palonosetron is both more effective than first generation 5-HT3RAs and safer, as it results in a smaller prolongation of the QTc interval, compared to other 5-HT3RAs.

Evaluating an Oncology Systemic Therapy Computerized Physician Order Entry System Using International Guidelines

Chemotherapy is prone to medication error resulting from complexities in ordering and administration. Computerized physician order entry (CPOE) has been established as an important tool to minimize such errors and hence improve patient safety. As a leading Canadian advisory body in oncology, Cancer Care Ontario (CCO) has been a champion in developing and implementing its own cancer systemic therapy CPOE, the Oncology Patient Information System (OPIS). This article reviews and consolidates principles for oncology CPOE systems as found in the literature and in guidelines created by three international oncology organizations (American Society of Clinical Oncology, Clinical Oncological Society of Australia, and CCO). It then evaluates OPIS by these standards and provides a working example of what a cancer CPOE system should look like. This document can therefore be used as a framework to help develop and evaluate cancer CPOE platforms in different national settings. As end users, oncologists are considered key stakeholders in developing such systems and thus should be well informed about CPOE principles to help make decisions on the appropriate implementation of these platforms in their local practice settings. In addition, oncologists are also important champions for the successful uptake of oncology CPOE platforms and would benefit from a better understanding of whether proposed or existing local CPOE systems meet established standards.

Aprepitant and granisetron for the prophylaxis of radiotherapy-induced nausea and vomiting after moderately emetogenic radiotherapy for bone metastases: a prospective pilot study.

PURPOSE We evaluated the novel combination of aprepitant and granisetron for the prophylaxis of radiotherapy-induced nausea and vomiting (rinv) among patients receiving moderately-emetogenic radiotherapy for thoracolumbar bone metastases. METHODS In this single-centre two-arm nonrandomized prospective pilot study, patients undergoing single-fraction radiotherapy (8 Gy) received aprepitant 125 mg and granisetron 2 mg on the day of radiotherapy and aprepitant 80 mg on each of the first 2 days after the day of radiotherapy. Patients undergoing multiple-fraction radiotherapy (20 Gy in 5 fractions) received aprepitant 125 mg on day 1 of radiotherapy, aprepitant 80 mg on days 3 and 5 of radiotherapy, and granisetron 2 mg on every day of radiotherapy. Symptoms and total medication intake were recorded daily during the acute phase (day 1 of radiotherapy until the first day after the last day of radiotherapy), and the delayed phase (days 2-10 after the last day of radiotherapy). Control of vomiting, retching, and nausea was defined as no symptoms and no use of rescue medication. RESULTS Control rates for single-fraction patients (n = 13) were 100% for acute nausea, 62% for delayed nausea, 100% for acute vomiting and retching, and 85% for delayed vomiting and retching. Control rates for multiple-fraction patients (n = 6) were 67% for acute nausea, 83% for delayed nausea, 67% for acute vomiting and retching, and 83% for delayed vomiting and retching. No grade 3 or 4 toxicities attributable to the study intervention were observed. CONCLUSIONS The combination of aprepitant and granisetron was safe and efficacious for the prophylaxis of rinv after both single- and multiple-fraction moderately emetogenic radiotherapy for thoracolumbar bone metastases. Our results require confirmation in a larger population.

A comparison of the toxicity and tolerability of two intraperitoneal chemotherapy regimens for advanced-stage epithelial ovarian cancer

OBJECTIVES Randomized controlled trials (RCTs) in optimally cytoreduced epithelial ovarian cancer (EOC) patients have demonstrated an impressive survival benefit of intraperitoneal (IP) platinum over intravenous (IV), but its use has been limited by significant toxicity from cisplatin. The aim of this study was to compare the toxicity and tolerability of IP cisplatin to IP carboplatin in women with optimally cytoreduced EOC. METHODS Retrospective analysis of 141 women with EOC who underwent optimal surgical cytoreduction followed by IV paclitaxel and IP cisplatin or IP carboplatin was performed. Toxicities of the two treatment regimens were compared. As a secondary outcome, overall survival (OS) and progression-free survival (PFS) probabilities were obtained using the Kaplan-Meier estimate; the log-rank test was used to compare survival curves. RESULTS Of the 141 patients, 77 (54.6%) received IP cisplatin and 64 (45.4%) received IP carboplatin. Eighty-six percent received at least 4 cycles of IP chemotherapy. IP cisplatin was associated with significantly more grade 3 nausea and vomiting (10.4% vs. 1.6%, p=0.033), grade 3 neuropathy (7.8% vs. 0%, p=0.013) and grade 2-3 neutropenia (22.1% vs. 9.4%, p=0.042). No difference in PFS (p=0.602) or OS (p=0.107) was found between the groups. CONCLUSION IP chemotherapy had a high completion rate in both groups of patients. IP carboplatin required a less resource intense protocol and was tolerated better than IP cisplatin with less gastrointestinal, neurologic and hematologic toxicities.

Efficacy of granisetron and aprepitant in a patient who failed ondansetron in the prophylaxis of radiation induced nausea and vomiting: a case report.

BACKGROUND Radiotherapy-induced nausea and vomiting (RINV) is a toxicity that can occur in 40-80% of individuals who receive radiation treatment. Current guidelines recommend 5-hydroxytryptamine3 receptor antagonists (5-HT3 RAs) for prophylaxis of RINV for moderate and highly emetogenic radiotherapy; however, certain patients may suffer from RINV despite prophylaxis. CASE PRESENTATION This report details the case of a 47-year-old female with extensive bony involvement to the spine from breast cancer presenting with lower back pain. CASE MANAGEMENT To palliate her symptoms, the patient underwent a course of irradiation to the lumbar spine and was prescribed ondansetron as an antiemetic. However, the patient experienced severe nausea and emesis and was subsequently switched to granisetron and aprepitant. CASE OUTCOME The patient completed the remainder of the radiation treatment with no further emesis and minimal nausea, representing the first documented success of granisetron and aprepitant for RINV after failure on ondansetron. CONCLUSIONS In chemotherapy, switching 5-HT3 RAs after failure on the first is successful in preventing chemotherapy-induced nausea and vomiting (CINV), yet this has not been previously reported in radiation. In this patient, granisetron and aprepitant were successful in substantially reducing nausea and preventing further emesis, and may represent an alternative antiemetic regimen for RINV prophylaxis and salvage.

Oral Anticancer Medication Adherence, Toxicity Reporting, and Counseling: A Study Comparing Health Care Providers and Patients

PURPOSE Oral anticancer medications (OACMs) have created new treatment opportunities, but also challenges for patients and practitioners. We aimed to compare health care provider (HCP) and patient perceptions on OACM adherence, toxicity reporting, and patient educational needs. METHODS An online survey for HCPs and paper survey for patients were analyzed using descriptive statistics. Bivariate analysis using the χ(2) test was used for some questions. RESULTS There were 169 HCP and 143 patient responses; 91% of patients reported taking their OACMs as prescribed more than 75% of the time, but only 40% of HCPs believed their patients were as adherent; 97% of HCPs believed patients reported their adverse effects some or most of the time; 61% of patients reported toxicities sometimes, often, or very often, but 30% never or rarely reported; 66% of HCPs believed patients did not report toxicity because of fear of treatment interruption, compared with 2% of patients. HCPs (53%) and patients (62%) both believed adverse effect tolerance was a common reason not to report. Most HCPs (70%) believed patients reported adverse effects first to a nurse. Patients seemed to report equally to nurses (42%) and oncologists (38%). Both HCPs and patients favored paper-based educational materials and call-back programs. CONCLUSION This study highlights disparities in patient and HCP perceptions of OACM adherence principles and toxicity reporting. Opportunities for improved patient education are identified, particularly around reporting significant toxicities. Different HCPs may benefit from complimentary counseling tools to encompass the entire spectrum of patient needs and provider practice.

Latest advances in the management of radiation-induced pain flare, nausea and vomiting

Palliative radiotherapy (RT) is an effective treatment for symptomatic bone metastases. However, pain flare, nausea and vomiting are common adverse effects associated with this treatment. The management of pain flare and radiation-induced nausea and vomiting (RINV) are important endpoints in palliative care. Our report documents the incidence, clinical importance, and advances in the management of these two adverse-effects. We recommend that antiemetic prophylaxis be given based on emetic risk category as outlined in the American Society of Clinical Oncology (ASCO) guidelines. Newer antiemetics investigated in the chemotherapy setting should also be studied in the radiation setting. As there are no guidelines for the use of pain flare prophylaxis at present, further research in this area is needed.

Retrospective review of the incidence of monitoring blood glucose levels in patients receiving corticosteroids with systemic anti-cancer therapy

BACKGROUND Corticosteroids are used adjuvant to certain chemotherapy regimens, either as an antiemetic, to reduce other side effects, or to enhance cancer treatment. Additionally, they are frequently used for symptom control in cancer patients with end stage disease. Corticosteroid use may induce hyperglycemia in approximately 20-50% of patients, which may negatively affect patient outcomes. OBJECTIVE To determine the frequency of blood glucose monitoring in patients with and without diabetes receiving continuous corticosteroids with chemotherapy, and to determine the incidence of treatment-emergent abnormal blood glucose levels and steroid-induced diabetes mellitus (DM). METHODS A retrospective review was conducted for 30 genitourinary (GU) cancer patients who were treated with continuous oral corticosteroids as part of their chemotherapy regimen. The Canadian Diabetes Association (CDA) criterion for diagnosis of diabetes was applied to categorize patients into two distinct groups, patients with diabetes and patients without diabetes. This categorization was made based on glucose measurements completed prior to commencement of corticosteroid therapy. Glucose monitoring was defined as receiving a laboratory blood glucose test before first chemotherapy administration along with a test within a week of each subsequent treatment cycle. The CDA criteria for diagnosis of pre-diabetes and diabetes was used to classify glucose levels as hyperglycemic. RESULTS The mean incidence of blood glucose monitoring was 19% and 76% in patients with diabetes and patients without diabetes, respectively. Approximately, 40% of patients with diabetes required an adjustment to their diabetes management and a further 20% required hospitalization. Fifteen patients without diabetes received a fasting blood glucose test, of which 40% had abnormal blood glucose results; half of these fell into the pre-diabetic range and half in the diabetic range. Ten patients without diabetes were tested for diabetes using the CDA criteria for diabetes diagnosis during or after their chemotherapy, of which 30% developed diabetes. CONCLUSIONS In order to optimize patient care, blood glucose levels should be monitored in all patients receiving continuous oral corticosteroids as part of their chemotherapy. Future studies should be conducted prospectively to determine the most effective manner of monitoring in order to implement screening guidelines and avoid unnecessary morbidity.

Olanzapine for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting (CINV): a retrospective study

BACKGROUND While the efficacy of olanzapine in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) has been documented, the literature on the use of olanzapine as a rescue medication for breakthrough CINV has been scarce. The following study retrospectively evaluated the safety and efficacy of olanzapine for the treatment of breakthrough CINV. The efficacy and safety of olanzapine in the prophylactic setting was also examined in a smaller cohort. METHODS Electronic medical records of adult patients aged >17 years receiving a prescription for olanzapine from the Odette Cancer Centre Pharmacy at Sunnybrook Hospital between January 2013 and June 2015 were reviewed retrospectively. Inclusion criteria required receiving one or more doses of olanzapine for the rescue or prophylaxis of CINV and documentation of the outcome. RESULTS A total of 154 patients and 193 treatment cycles were included in the breakthrough setting, while a total of 16 patients and 20 treatment cycles were included in the prophylaxis setting. In the breakthrough setting, 88% of cases experienced improved nausea, while 21% of cases reported improved vomiting. In the prophylactic setting, 100% of cases experienced improved nausea, while 65% achieved improved vomiting. A total of 43% of cases in the breakthrough setting and 65% of cases in the prophylactic setting experienced sedation. CONCLUSIONS Olanzapine is effective in improving CINV in both the prophylactic and breakthrough settings. The safety, efficacy, and appropriate dosage of olanzapine for the rescue of breakthrough CINV should be prospectively evaluated in a randomized controlled trial (RCT).