Franziska Jahn

International antiemetic guidelines on chemotherapy induced nausea and vomiting (CINV) : content and implementation in daily routine practice

Over the past decades major improvements in the management of chemotherapy induced nausea and vomiting (CINV) were obtained. With the correct use of antiemetic drugs, CINV can be prevented in almost 70%, and even up to, 80% of patients. Treatment guidelines enable physicians to integrate the latest clinical research into their daily practice. The large volume of rapidly evolving clinical data has been summarised and incorporated into treatment recommendations by well-known and reliable institutions. These organisations include the Multinational Association of Supportive Care in Cancer (MASCC), the European Society of Medical Oncology (ESMO), the American Society for Clinical Oncology (ASCO), and National Comprehensive Cancer Network (NCCN). However, despite the availability of these guidelines, there is an emerging evidence that adherence to, and implementation of, treatment recommendations is less than optimal. This review will especially focus on the content of the current antiemetic guidelines and will address the important question of how these guidelines are implemented in routine practice.

Recent developments in the prevention of chemotherapy-induced nausea and vomiting (CINV): a comprehensive review

The prevention of chemotherapy-induced nausea and vomiting (CINV) has been revolutionized over the past 25 years. Guideline-based treatment means that vomiting can be prevented in the majority, but not in all patients. Therefore, antiemetic research continues with the goal of optimizing CINV control for all patients. This comprehensive review summarizes the research efforts in this field over the past few years. Emerging from this research are two new antiemetic agents, netupitant/palonosetron, the first antiemetic combination agent and rolapitant, a new NK1RA. In addition, studies have evaluated the benefits of olanzapine and ginger, explored optimal combinations of agents for delayed CINV prevention, confirmed that dexamethasone-sparing regimens are effective, and demonstrated the value of NK1RAs in high-dose chemotherapy settings as well as with certain moderately emetogenic chemotherapies such as carboplatin. Research has also validated the correlation between antiemetic guideline adherence and improved CINV control. Finally, regulatory authorities have utilized extreme caution in retiring some 5-HT3RAs or decreasing their maximum dose.The prevention of chemotherapy-induced nausea and vomiting (CINV) has been revolutionized over the past 25 years. Guideline-based treatment means that vomiting can be prevented in the majority, but not in all patients. Therefore, antiemetic research continues with the goal of optimizing CINV control for all patients. This comprehensive review summarizes the research efforts in this field over the past few years. Emerging from this research are two new antiemetic agents, netupitant/palonosetron, the first antiemetic combination agent and rolapitant, a new NK1RA. In addition, studies have evaluated the benefits of olanzapine and ginger, explored optimal combinations of agents for delayed CINV prevention, confirmed that dexamethasone-sparing regimens are effective, and demonstrated the value of NK1RAs in high-dose chemotherapy settings as well as with certain moderately emetogenic chemotherapies such as carboplatin. Research has also validated the correlation between antiemetic guideline adherence and improved CINV control. Finally, regulatory authorities have utilized extreme caution in retiring some 5-HT3RAs or decreasing their maximum dose.

Radiation induced nausea and vomiting.

Radiation induced nausea and vomiting (RINV) is a frequent complication of radiotherapy and still often underestimated by radiation oncologists. Fractionated RT may involve up to 40 fractions over a 6-8 weeks period, and prolonged symptoms of nausea and vomiting affect quality of life. Approximately, 50-80 percent of patients undergoing radiotherapy (RT) will experience these symptoms if no appropriate prophylaxis is applied. The incidence and severity are influenced by the specific RT regimen and by patient-specific factors. Patients should receive antiemetic prophylaxis as suggested by the international antiemetic guidelines based upon a risk assessment, taking especially into account the planned radiotherapy regimen. In this field the guideline from the Multinational Association of Supportive Care in Cancer (MASCC)/European Society of Clinical Oncology (ESMO) and the American Society of Medical Oncology (ASCO) guidelines are wildly endorsed. The emetogenicity of radiotherapy regimens and recommendations for the appropriate use of antiemetics including 5-hydroxytryptamine (5-HT3) receptor antagonists and steroids will be discussed in regard to the applied radiotherapy or radiochemotherapy regimen.

Review of the efficacy of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in a range of tumor types

Chemotherapy regimens differ according to the tumor type being treated and are associated with varying degrees of emetogenic potential. Since the distribution of risk factors for chemotherapy-induced nausea and vomiting differs across tumor types, it is important to understand the efficacy of antiemetic regimens in multiple patient populations. To characterize treatment response in patients with various malignancies (e.g., breast, gastrointestinal, genitourinary, and lung) treated with either highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) regimens, a pooled analysis of patient-level data from 4 large randomized trials was performed (N=2813). Patients receiving an antiemetic regimen containing aprepitant, ondansetron, and dexamethasone were compared with patients receiving an active-control antiemetic regimen containing ondansetron plus dexamethasone. In all tumor types analyzed, complete responses were observed in a higher proportion of HEC-treated patients receiving aprepitant compared with active-control patients (genitourinary [61.5% vs 40.6%, P<0.001], gastrointestinal [68.2% vs 44.7%, P=0.013], and lung cancers [73.5% vs 52.8%, P<0.001]). For MEC-treated patients, complete response rates were also higher for aprepitant patients than active-control patients for all tumor types, with a significant difference noted among patients with breast cancer (54.9% vs 43.9%, P<0.0001). The proportion of patients with no vomiting was higher in both HEC- and MEC-treated patients. While results of previous studies provide support for the use of antiemetic regimens that include aprepitant, a selective 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone, this analysis demonstrates the consistent efficacy of aprepitant as part of an antiemetic regimen across different tumor types and chemotherapy regimens.

Safety and Efficacy of Liposomal Cytarabine in the Treatment of Neoplastic Meningitis

Objectives: Although rare, neoplastic meningitis (NM) has been increasingly observed in patients with cancer due to the prolonged course of the disease. Intrathecal chemotherapy with methotrexate or cytarabine with repeating injection schedules of 2-3 times per week is currently the mainstay of treatment. An efficacious and comfortable treatment alternative might be represented by liposomal cytarabine. Methods: In this retrospective study, we reviewed all patients with NM due to solid tumors or hematological malignancies treated with liposomal cytarabine at our institution between March 2004 and September 2011. The primary endpoint was treatment response, which was defined as improvement in neurological symptoms and/or conversion of the initial cerebrospinal fluid cytology and/or response in the radiological findings. The main secondary endpoint was safety. Results: Fifty-one adult patients were evaluable for safety and 44 patients for efficacy. In 36 patients (81.8%), a treatment response was achieved. The median overall survival after diagnosis of NM was 11 months (95% confidence interval 8.8-13.2). Adverse events grade 1-4 occurred in 31 patients (60.8%), whereas grade 3-4 occurred in 18 patients (35.3%). Conclusion: The encouraging efficacy and safety data obtained in our analysis and the convenient administration schedule make intrathecal liposomal cytarabine a favorable treatment option for NM patients.

Prophylactic Management of Radiation-Induced Nausea and Vomiting

The incidence of nausea and vomiting after radiotherapy is often underestimated by physicians, though some 50–80% of patients may experience these symptoms. The occurrence of radiotherapy-induced nausea and vomiting (RINV) will depend on radiotherapy-related factors, such as the site of irradiation, the dosing, fractionation, irradiated volume, and radiotherapy techniques. Patients should receive antiemetic prophylaxis as suggested by the international antiemetic guidelines based upon a risk assessment, taking especially into account the affected anatomic region and the planned radiotherapy regimen. In this field the international guidelines from the Multinational Association of Supportive Care in Cancer (MASCC)/European Society of Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) guidelines as well as the National Comprehensive Cancer Network (NCCN) are widely endorsed. The emetogenicity of radiotherapy regimens and recommendations for the appropriate use of antiemetics including 5-hydroxytryptamine (5-HT3) receptor antagonists, steroids, and other antiemetics will be reviewed in regard to the applied radiotherapy or radiochemotherapy regimen.

Neuropharmacology and management of chemotherapy-induced nausea and vomiting in patients with breast cancer.

Advances in our understanding of the pathophysiology of chemotherapy-induced nausea and vomiting (CINV), the identification of patient risk factors, and the development of new antiemetics have led to significant improvements in CINV prevention. With the correct use of antiemetic drugs, CINV can be prevented in the majority of patients. Extensive clinical data have been considered in the development of antiemetic treatment recommendations by reliable institutions such as the Multinational Association of Supportive Care in Cancer, the European Society of Medical Oncology and the American Society for Clinical Oncology. These guidelines are intended to enable physicians to incorporate the latest clinical research into their daily practice, considering CINV prevention as part of an optimal patient-centered approach to cancer management. Yet despite the availability of these guidelines, there is emerging evidence that implementation of treatment recommendations is suboptimal. Recently, guideline committees gave special consideration to patient-related risk factors (young, females) contributing to the emetogenic potential for patients receiving anthracycline and cyclophosphamide-based chemotherapy. As women with breast cancer represent a particularly challenging population regarding emesis control, it is especially important that treatment recommendations are followed. This review focuses on the content of the current antiemetic guidelines, addressing the importance of how these are intended to be implemented in routine clinical practice.

2016 updated MASCC/ESMO consensus recommendations: prevention of radiotherapy-induced nausea and vomiting

PurposeRadiotherapy-induced nausea and vomiting (RINV) are distressing symptoms. Evidence-based guidelines should facilitate the prescription of the best possible antiemetic prophylaxis. As part of the MASCC/ESMO Antiemetic Guidelines Update 2016, a thorough review of the literature concerning RINV since the 2009 update was required.MethodsA systematic review of the literature including data published from June 2009 to May 2015 was performed. Committee VII (RINV) under the MASCC/ESMO Antiemetic Guidelines Update Committee assessed the literature.ResultsThe searches yielded 926 records, 906 records were excluded, leaving 20 records for full text assessment, and 18 publications were finally included. The only fully published randomized studies in prevention of RINV were two negative studies in acupuncture and green tea, respectively. No data to support new recommendations for antiemetic prophylaxis in RINV was available. However, based on expert opinions, the committee agreed on changes in emetic risk level for certain sites of irradiation.ConclusionsThe serotonin receptor antagonists are still the corner stone in antiemetic prophylaxis of nausea and vomiting induced by high and moderate emetic risk radiotherapy. The studies available since the last update did not change recommendations for antiemetic prophylaxis. The emetogenicity of craniospinal radiotherapy was reclassified from low to moderate emetic level along with some other minor changes. In the future, RINV prophylaxis in single fraction, multiple fraction, and in concomitant chemo-radiotherapy still need to be explored with regard to the different classes and combinations of antiemetic drugs.

Trabectedin: Supportive care strategies and safety profile.

Trabectedin is an approved antineoplastic agent for the treatment of adult patients with advanced soft tissue sarcomas or in combination with pegylated liposomal doxorubicin (PLD) in patients with relapsed platinum sensitive ovarian cancer. The mechanism of action is still not fully understood but many typical side effects seen with other chemotherapy drugs are less common, mild or unreported. Although this apparent favorable safety profile suggests a well-tolerated and manageable therapeutic option in the palliative care setting, trabectedin does have specific adverse side effects which can be hazardous for individual patients. The most commonly observed toxicities with trabectedin include neutropenia, nausea, vomiting, and increases in liver transaminases, anemia, fatigue, thrombocytopenia, anorexia and diarrhea. However, for most patients the appropriate use of supportive care strategies can reduce or overcome these side effects. We present a concise review of the safety data of trabectedin with the corresponding overview of the supportive care strategies.

Calcium and Magnesium Infusions for the Prevention of Oxaliplatin-Induced Peripheral Neurotoxicity: A Systematic Review

Objectives: The objective of this systematic review was to summarize the evidence of calcium and magnesium (CaMg) infusions in the prevention of oxaliplatin-induced neuropathy on the basis of prospective randomized controlled trials (RCTs). Methods: A systematic search included MEDLINE and CENTRAL, plus major oncology conferences, and identified RCTs evaluating CaMg. Efficacy endpoints were chronic neurotoxicity measured with National Cancer Institute Common Terminology Criteria for Adverse Events grades and the oxaliplatin-specific scale (OSS). Data were synthesized using a random effects model. Results: A total of 5 trials with 694 evaluable patients were included in this analysis. The pooled result stated the outcome of the largest study included [Loprinzi et al.: J Clin Oncol 2014;32:997-1005], in which no differences were detected for the incidence of grade ≥2 neuropathy between those receiving CaMg infusions and controls [relative risk (RR) 0.81, 95% confidence interval (CI) 0.60-1.11]. Only 2 studies (n = 52) quoted an incidence of chronic neurotoxicity for all grades (with a pooled RR of 0.95 and 95% CI 0.69-1.32), with substantial statistical heterogeneity. Three studies reported an actual incidence of the OSS but, due to the detected substantial statistical heterogeneity, the studies were not pooled. Conclusion: The results of our systematic review demonstrated the nonbeneficial effect of CaMg infusions for the prevention of oxaliplatin-induced peripheral neuropathy.