FLOT; To Be Treated as a Highly Emetogenic Regimen or a Moderately Emetogenic One? Comparison of the Emetogenic Potential of FLOT versus FOLFOX and TAC Regimens

PurposeThe current study aimed at investigating the efficacy of aprepitant-containing triple antiemetic regimen in FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel) recipients as well as the emetogenic potential of FLOT regimen, through comparison of nausea and vomiting rates in a moderately emetogenic chemotherapy, FLOT, and a highly emetogenic chemotherapy recipients.StudyPatients planned to receive one of FLOT, FOLFOX (Fluorouracil+Leucovorin+ Oxaliplatin/moderate-emetic-risk), or TAC (Docetaxel+Doxorubicin+Cyclophosphamide/high-emetic-risk) regimens were recruited. All patients were treated with the same triple antiemetic regimen containing aprepitant.ResultsA total of 165 chemotherapy-naïve patients (52 FLOT recipients) were eligible to enter the study. At the end of day five, “complete response” (primary efficacy endpoint) was achieved by 84.6%, 63.5%, and 61.5% of the FLOT-receiving patients in acute, delayed, and overall phases, respectively. A significant difference was seen among the odds of FLOT recipients and FOLFOX recipients concerning “complete response” achievement in delayed (p=0.014) and overall (p=0.017) phases, “no emesis” in delayed (p=0.018) and overall (p=0.010) phases, also “complete protection” in acute (p=0.023), delayed (p=0.009) and overall (p=0.006) phases; however, the difference between the odds of FLOT recipients and TAC recipients, in relation to achieving these endpoints was insignificant. FLOT group showed significantly faster time-to-antiemetic regimen failure and time-to-first emetic episode in comparison to the FOLFOX group, which was insignificant in comparison to the TAC group.ConclusionAccording to the findings, FLOT has to be considered as a high-emetic-risk regimen. To better management of highly emetogenic regimens, antiemetic guidelines recommend adding olanzapine to aprepitant-containing triple antiemetic regimen besides continuing dexamethasone and olanzapine administration on days 2-4.

Randomized, Double-Blind, Phase III Study of Fosnetupitant Versus Fosaprepitant for Prevention of Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: CONSOLE

PURPOSE We evaluated the efficacy and safety of fosnetupitant (FosNTP) versus fosaprepitant (FosAPR) for preventing highly emetogenic chemotherapy-induced nausea and vomiting. This phase III study was the first head-to-head comparison between two different neurokinin-1 receptor antagonists in combination with palonosetron and dexamethasone. PATIENTS AND METHODS Patients scheduled to receive cisplatin-based chemotherapy were randomly assigned 1:1 to FosNTP 235 mg or FosAPR 150 mg in combination with palonosetron 0.75 mg and dexamethasone. The primary end point was overall (0-120 hours) complete response (CR; no emetic event and no rescue medication) rate, stratified by sex and age category, to show the noninferiority of FosNTP to FosAPR (noninferiority margin, –10% for the difference in the overall CR rate). RESULTS Overall, 795 patients were randomly assigned, of whom 785 received the study drug (FosNTP [N = 392] v FosAPR [N = 393]) and were evaluated for efficacy and safety. The overall CR rate was 75.2% versus 71.0%, respectively (Mantel-Haenszel common risk difference, 4.1%; 95% CI, –2.1% to 10.3%), demonstrating noninferiority of FosNTP to FosAPR. The CR rates in the acute (0-24 hours), delayed (24-120 hours), and beyond delayed (120-168 hours) phases, and at 0-168 hours were 93.9% versus 92.6%, 76.8% versus 72.8%, 86.5% versus 81.4%, and 73.2% versus 66.9%, respectively. The incidence rates of treatment-related adverse events with FosNTP versus FosAPR were 22.2% versus 25.4%, whereas adverse events or treatment-related adverse events relevant to injection site reactions were 11.0% versus 20.6% ( P < .001) and 0.3% versus 3.6% ( P < .001), respectively. CONCLUSION FosNTP demonstrated noninferiority to FosAPR, with a favorable safety profile and lower risk for injection site reactions. Thus, FosNTP is valuable in the prophylaxis of acute, delayed, and beyond delayed chemotherapy-induced nausea and vomiting.

Incidence of Chemotherapy-Induced Nausea and Vomiting and Antiemetic Guideline Compliance in Chinese Real Clinical Setting: A Cross-Sectional Multicenter Survey

Background This survey aims to investigate the incidence of chemotherapy-induced nausea and vomiting (CINV) in Chinese real clinical setting and evaluate the effect of guideline-consistent CINV prophylaxis (GCCP) and guideline-inconsistent CINV prophylaxis (GICP) on incidence of complete response (CR) of CINV. Materials and Methods A cross-sectional nationwide multicenter study assessing the guideline consistency and CINV incidence of patients was conducted at a total of 32 large medical centers from 26 provinces across the west,east༌northeast and middle part of China between April and May 2021. Result Data for 2964 patients were analyzed. Patients treated with moderately emetogenic chemotherapy (MEC) were more prone to experience CINV during the acute phase compared to those receiving highly emetogenic chemotherapy (HEC); patients receiving low or minimally emetogenic chemotherapy (L/mEC) were least likely to experience CINV during the overall phase among the whole study population. The prevalence of GCCP was 29.2% in the whole study population, and 13.6%, 35.7% and 45.1% for the patients receiving HEC, MEC and L/mEC, respectively. For patients receiving HEC and MEC, GCCP increased incidence of CR during both delayed and overall phases. For those receiving L/mEC and GICP, incidence of CR was not higher than that of patients receiving L/mEC and GCCP. Conclusion This study revealed Chinese CINV status, the prevalence of GCCP in the real clinical setting and the association between GCCP and CR rate for the first time. The findings indicate that prescribing antiemetics in compliance with guidelines for all patients receiving chemotherapy is strongly suggested.

The Balance Between the Effectiveness and Safety for Chemotherapy-Induced Nausea and Vomiting of Different Doses of Olanzapine (10 mg Versus 5 mg): A Systematic Review and Meta-Analysis

IntroductionThe aim of this study is to rigorously review the efficacy and safety of olanzapine in chemotherapy-induced nausea and vomiting (CINV) settings including (1) at 5- and 10-mg doses, and (2) the setting of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).MethodsEmbase, Pubmed, and Cochrane Library were searched from the establishment of the database through April 18, 2021. The primary efficacy endpoints were the rate of complete response (CR; no emesis and no rescue), 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 complete control (CC, no nausea, and no emesis), for each phase. Safety endpoints were the rate of somnolence, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) criteria. The Mantel–Haenszel, random, or fixed-effect 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.ResultNine studies reported the use of 10 mg olanzapine to prevent CINV; three studies reported the use of 5 mg olanzapine to prevent CINV. When olanzapine was administered at 10 mg for HEC patients, the six endpoints were statistically and clinically better than the control group. For MEC patients, four out of six endpoints were better than the control group. When olanzapine is administered at 5 mg for MEC patients, four endpoints have statistical and clinical advantages. The sedative effects of 10 and 5 mg olanzapine were statistically more significant than those of the control group. The sedative effect of the 10-mg olanzapine group was more significant than that of the 5-mg olanzapine group, both statistically and clinically.Conclusion5 mg olanzapine may be as effective as 10 mg olanzapine for patients with HEC and MEC, and its sedative effect is lower than 10 mg olanzapine. Fewer studies on 5 mg olanzapine have led to uncertain data. In the future, more randomized controlled trials of 5 mg olanzapine are needed to study the balance between the effectiveness and safety of olanzapine.