The present review summarizes and discuss the most recent updated antiemetic consensus.
Two new neurokinin (NK)1-receptor antagonists, netupitant and rolapitant, have been approved by the Food and ...Drug Administration and the European Medicines Agency and incorporated in the latest versions of the MASCC/ESMO, ASCO, and NCCN guidelines. Guidelines all recommend a combination of a serotonin (5-HT)3-receptor antagonist, dexamethasone, and a NK1-receptor antagonist in patients receiving highly emetogenic chemotherapy (HEC) with the addition of the multireceptor targeting agent, olanzapine, as an option in cisplatin or anthracycline-cyclophosphamide chemotherapy. A combination of a 5-HT3-receptor antagonist, dexamethasone, and a NK1-receptor antagonist is also recommended in patients receiving carboplatin-based chemotherapy, although based on a lower level of evidence. In spite of the development of new antiemetics, nausea has remained a significant adverse effect. Olanzapine is an effective antinausea agent, but sedation can be a problem. Therefore, the effect and tolerability of multitargeting, nonsedative agents like amisulpride, should be explored.
Guidelines recommend a combination of a 5-HT3-receptor antagonist, dexamethasone, and an NK1-receptor antagonist in HEC and carboplatin-based chemotherapy. The addition of olanzapine can be useful in cisplatin-based and anthracycline-cyclophosphamide-based chemotherapy in particular if the main problem is nausea.
To provide evidence-based guidance on the clinical management of cancer cachexia in adult patients with advanced cancer.
A systematic review of the literature collected evidence regarding ...nutritional, pharmacologic, and other interventions, such as exercise, for cancer cachexia. PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and systematic reviews of RCTs published from 1966 through October 17, 2019. ASCO convened an Expert Panel to review the evidence and formulate recommendations.
The review included 20 systematic reviews and 13 additional RCTs. Dietary counseling, with or without oral nutritional supplements, was reported to increase body weight in some trials, but evidence remains limited. Pharmacologic interventions associated with improvements in appetite and/or body weight include progesterone analogs and corticosteroids. The other evaluated interventions either had no benefit or insufficient evidence of benefit to draw conclusions on efficacy. Limitations of the evidence include high drop-out rates, consistent with advanced cancer, as well as variability across studies in outcomes of interest and methods for outcome assessment.
Dietary counseling may be offered with the goals of providing patients and caregivers with advice for the management of cachexia. Enteral feeding tubes and parenteral nutrition should not be used routinely. In the absence of more robust evidence, no specific pharmacological intervention can be recommended as the standard of care; therefore, clinicians may choose not to prescribe medications specifically for the treatment of cancer cachexia. Nonetheless, when it is decided to trial a drug to improve appetite and/or improve weight gain, currently available pharmacologic interventions that may be used include progesterone analogs and short-term (weeks) corticosteroids.
Chemotherapy-induced nausea and vomiting (CINV) are still two of the most feared side effects of cancer therapy. Although major progress in the prophylaxis of CINV has been made during the past 40 ...years, nausea in particular remains a significant problem. Older patients have a lower risk of CINV than younger patients, but are at a higher risk of severe consequences of dehydration and electrolyte disturbances following emesis. Age-related organ deficiencies, comorbidities, polypharmacy, risk of drug-drug interactions, and lack of compliance all need to be addressed in the older patient with cancer at risk of CINV. Guidelines provide evidence-based recommendations for the prophylaxis of CINV, but none of these guidelines offer specific recommendations for older patients with cancer. This means that the recommendations may lead to overtreatment in some older patients. This review describes the development of antiemetic prophylaxis of CINV focusing on older patients, summarizes recommendations from antiemetic guidelines, describes deficiencies in our knowledge of older patients, summarizes necessary precautions, and suggests some future perspectives for antiemetic research in older patients.
Introduction
The aim of this study is to rigorously review the efficacy and safety of olanzapine in defined hematology oncology settings including (1) the setting of highly emetogenic chemotherapy ...(HEC) and moderately emetogenic chemotherapy (MEC) settings (2) at 5 mg and 10 mg doses, and (3) for response rates for use in the acute, delayed, and overall settings post-MEC and HEC.
Methods
Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched through April 23, 2020. The primary efficacy endpoints were the rate of complete response, in the acute (0–24 h post-chemotherapy), delayed (24–120 h post-chemotherapy), and overall (0–120 h post-chemotherapy) phases. The secondary efficacy endpoints were the rates of no nausea and no emesis, for each phase. Safety endpoints were the rate of no serious adverse events (i.e., no grade 3 or 4 toxicities), as assessed by Common Terminology Criteria for Adverse Events (CTCAE) criteria. The Mantel-Haenszel, random-effects analysis model was used to compute risk ratios and accompanying 95% confidence intervals for each endpoint. For endpoints that statistically favored one arm, absolute risk differences were computed to assess whether there is a 10% or greater difference, used as the threshold for clinical significance by MASCC/ESMO. Fragility indices were also calculated for each statistically significant endpoint, to quantitatively assess the robustness of the summary estimate. A cumulative meta-analysis was conducted for each efficacy meta-analysis with more than 5 studies, also using the Mantel-Haenszel random-effects analysis model.
Results
Three studies reported on olanzapine for the rescue of breakthrough chemotherapy-induced nausea and vomiting (CINV); 22 studies reported on olanzapine in the prophylactic setting. For studies reporting on HEC patients, olanzapine-containing regimens were statistically and clinically superior in seven of nine efficacy endpoints in the prophylaxis setting. When olanzapine is administered at a 10-mg dose, it is statistically and clinically superior to control patients in eight of nine endpoints among adults. Olanzapine may be effective in the MEC setting and when administered at 5-mg doses, but the paucity of data leads to notable uncertainty.
Conclusion
Further RCTs are needed in the setting of MEC patients and administration of olanzapine at a lower 5-mg dose, which may be given to reduce the sedative effect of olanzapine at 10 mg.
Nausea and vomiting are two of the most severe problems for patients treated with chemotherapy. Until the late 1970s, nausea and vomiting induced by chemotherapy was an almost neglected research ...area. With the introduction of cisplatin, the cytotoxin with the highest emetic potential, research was stimulated and has now resulted in the development of two new classes of antiemetics, the serotonin and neurokinin antagonists. A large number of trials have fine-tuned antiemetic therapy and made evidence-based recommendations possible for the majority of patients receiving chemotherapy. This Review discusses the pathophysiology of nausea and vomiting, the development of antiemetics, highlights some of the newest antiemetics, and finally summarizes recommendations from the evidence-based guidelines developed by the Multinational Association of Supportive Care in Cancer.
Age-related immune dysfunction (ARID) describes age-associated changes in immunity that may affect the efficacy of immunotherapy with checkpoint inhibitors. We evaluated the efficacy of treatment ...with ipilimumab (530 patients) or pembrolizumab (562 patients) in a Danish national cohort of metastatic melanoma patients.
We confirmed known prognostic biomarkers related to treatment with ipilimumab and found no impact of age on survival or progression-free survival. In patients treated with pembrolizumab, we also confirmed known prognostic biomarkers. Overall survival (OS) and progression-free survival was significantly higher in patients aged between 70 and 80 years compared with younger patients. In multivariate analysis with OS as end-point, age was shown to be an independent good prognostic biomarker in these patients. Survival in patients aged above 80 years was not better than in younger patients, probably because of increase in significant comorbidity.
Our analyses have revealed a higher survival rate when using drugs targeting PD1 in metastatic melanoma patients between the age of 70 and 80 years. ARID does not seem to negatively impact the efficacy of treatment with checkpoint inhibitors in metastatic melanoma patients. Despite these encouraging data for elderly patients, clinicians still need to carefully consider the higher risk of more serious outcomes of the immune-related adverse events in the elderly patient population, before deciding to treat old patients with checkpoint inhibitors.
•Large national cohort of metastatic melanoma patients treated with anti-CTLA4 or anti-PD1.•Age between 70 and 80 predicts better survival after treatment with anti-PD1 compared with younger patients.•Survival is not affected by age using anti-CTLA4 as checkpoint inhibitor in metastatic melanoma patients.
Purpose
This review summarizes the recommendations for the prophylaxis of acute and delayed nausea and vomiting induced by multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea ...and vomiting as agreed at the MASCC/ESMO Antiemetic Guidelines update meeting in Copenhagen in June 2015.
Methods
A systematic literature search using PubMed from January 01, 2009 through January 06, 2015 with a restriction to papers in English was conducted.
Results
There were three phase III randomized trials in patients undergoing high-dose chemotherapy and stem cell transplant and eight single arm non-randomized clinical studies (single in patients undergoing transplantation and one in patients receiving multiple-day chemotherapy treatment). We used a total of two randomized clinical trials in this guideline update. For patients receiving treatment for breakthrough chemotherapy-induced nausea and vomiting, a phase III randomized trial investigating the use of olanzapine versus metoclopramide in patients receiving highly emetogenic chemotherapy and a second single arm study looking at the effectiveness of olanzapine were identified.
Conclusions
It was concluded that for patients receiving high-dose chemotherapy with stem cell transplant, a combination of a 5-HT
3
receptor antagonist with dexamethasone and aprepitant (125 mg orally on day 1 and 80 mg orally on days 2 to 4) is recommended before chemotherapy.
For patients undergoing multiple-day chemotherapy-induced nausea and vomiting, a 5-HT
3
receptor antagonist, dexamethasone, and aprepitant, are recommended before chemotherapy for the prophylaxis of acute emesis and delayed emesis.
For patients experiencing breakthrough nausea and vomiting, the available evidence suggests the use of 10 mg oral olanzapine, daily for 3 days. Mild to moderate sedation in this patient population (especially elderly patients) is a potential problem with this agent.
Niraparib is an oral poly(adenosine diphosphate ADP-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of ...niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer.
In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2:1 ratio to receive niraparib (300 mg) or placebo once daily. The primary end point was progression-free survival.
Of 553 enrolled patients, 203 were in the gBRCA cohort (with 138 assigned to niraparib and 65 to placebo), and 350 patients were in the non-gBRCA cohort (with 234 assigned to niraparib and 116 to placebo). Patients in the niraparib group had a significantly longer median duration of progression-free survival than did those in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard ratio, 0.27; 95% confidence interval CI, 0.17 to 0.41), as compared with 12.9 months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59) and 9.3 months vs. 3.9 months in the overall non-gBRCA cohort (hazard ratio, 0.45; 95% CI, 0.34 to 0.61; P<0.001 for all three comparisons). The most common grade 3 or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which were managed with dose modifications.
Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of the presence or absence of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro; ClinicalTrials.gov number, NCT01847274 .).
Purpose
Olanzapine-containing regimens have been reported to be effective in preventing CINV following highly emetogenic chemotherapy (HEC), but it is unsure whether it is cost-effective. There has ...been no cost-effectiveness analysis conducted for olanzapine using costs from the USA. The aim of this study is to determine whether olanzapine-containing antiemetic regimens are cost-effective in patients receiving HEC.
Methods
A decision tree model was constructed to evaluate the cost and health outcomes associated with olanzapine-containing antiemetic regimens and otherwise-identical regimens. One-way sensitivity analyses were conducted to individually investigate the effect of (i) lower complete response (CR) rates of olanzapine, closer to non-olanzapine-containing regimens; (ii) higher FLIE scores for patients who achieved no/incomplete response, closer to FLIE scores of patients achieving a complete response; (iii) differing costs of olanzapine to reflect different costs per hospitals, globally, due to different insurance systems and drug costs; and (iv) varying costs for uncontrolled CINV, to account for varying durations of chemotherapy and accompanying uncontrolled CINV.
Results
Olanzapine regimens have an expected cost of $325.24, compared with $551.23 for non-olanzapine regimens. Meanwhile, olanzapine regimens have an expected utility/index of 0.89, relative to 0.87 for non-olanzapine regimens. Olanzapine-containing regimens dominate non-olanzapine-containing regimens even if CR of olanzapine-containing regimens fall to 0.63. Only when CR is between 0.60 and 0.62 is olanzapine both more effective and more costly.
Conclusion
Olanzapine-containing regimens are both cheaper and more effective in the prophylaxis of CINV in HEC patients, compared with non-olanzapine-containing regimens. Future CINV trial resources should be allocated to understand newer antiemetics and compare them to olanzapine-containing regimens as the control arm. Further analysis should use nationally representative data to examine medication costs by payer type.
Addition of aprepitant, a neurokinin-1 receptor antagonist (NK1RA), to an ondansetron and dexamethasone regimen improves prevention of chemotherapy-induced nausea/vomiting (CINV), particularly during ...the delayed phase (DP; 25 to 120 hours). Therefore, recommended antiemetic regimens include multiple-day NK1RA administration. Preliminary data suggested that single-dose aprepitant before chemotherapy could provide CINV protection throughout the overall risk phase (OP; 0 to 120 hours). This study compared a 3-day oral aprepitant schedule to a regimen containing a single dose of the intravenous NK1RA fosaprepitant.
A randomized, double-blind, active-control design was used to test whether fosaprepitant is noninferior to aprepitant. Patients receiving cisplatin ≥ 70 mg/m(2) for the first time received ondansetron and dexamethasone with a standard aprepitant regimen (125 mg on day 1, 80 mg on day 2, 80 mg on day 3) or a single-dose fosaprepitant regimen (150 mg on day 1). The primary end point was complete response (CR; no vomiting, no rescue medication) during OP. Secondary end points were CR during DP and no vomiting during OP. Accrual of 1,113 evaluable patients per treatment arm was planned to confirm noninferiority with expected CR of 67.7% and noninferiority margin of minus 7 percentage points.
A total of 2,322 patients were randomly assigned, and 2,247 were evaluable for efficacy. Antiemetic protection with aprepitant and fosaprepitant was equivalent within predefined bounds for noninferiority. Both regimens were well tolerated, although more frequent infusion site pain/erythema/thrombophlebitis was seen with fosaprepitant relative to aprepitant (2.7% v 0.3%, respectively).
Given with ondansetron and dexamethasone, single-dose intravenous fosaprepitant (150 mg) was noninferior to standard 3-day oral aprepitant in preventing CINV during OP and DP.
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