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.

Low Dose Olanzapine in the Prevention Carboplatin Induced Nausea and Vomiting: a Prospective Randomized Controlled Trial

Objective To perform a prospective randomized comparison of the efficacy and safety of low-dose 5mg olanzapine（OLZ） in preventing nausea and vomiting induced by carboplatin chemotherapy.Methods All patients with malignant tumors (n=113) who received carboplatin（AUC≥5）chemotherapy were randomly divided into two groups:triplet regimen group (n=56) and standard group (n=57). The patients in the olanzapine group received 5mg olanzapine combined with 5-HT3RA and dexamethasone(DXM) triplet antiemetic regimen, whereas those in the standard group received 5-HT3RA and DXM. The primary end-points of the study were the TC(total contral) during the OP(Overall phase, 0-120h), AP(acute phase, 0-24h) and DP(delayed phase, 25-120h) phase between combined 5mg olanzapine triplet regimen group and standard group. The secondary end-points were the TP (total protection) and CR (complete response) during OP, AP and DP phase between two groups. The first time to vomiting comparion between two groups was depicted by Kaplan-Meier curves. The impact of chemotherapy-induced nausea and vomiting (CINV) on the quality of life was assessed by the Functional Living Index-Emesis(FLIE). Olanzapine related side-effection was also recorded.Results: (1) The primary end-point TC rate were favorable 5mg olanzapine group than standard group during the OP 62.50% (35/56) vs 31.57% (18/57) P=0.001), AP 87.50% (49/56) vs 63.15% (36/57) P=0.003 and DP 64.28% (36/56) vs 33.33% (19/57) P=0.001 respectively. (2)The secondry end-points TP were 82.14% (46/56) vs 63.15%(36/57)(P=0.024),83.92%(47/56) vs 63.15%(36/57) (P=0.012) during the OP and DP but not get statistical significance during AP between two groups respectively.The CR rate does not get statistical significance between two groups during the three periods respectively, P>0.05;(3) It was observed longer time to first emesis in the olanzapine group than standard group from Kaplan-Meier curves.The no effection on life-quality (score≥108) assessed by FILE was 62.50% vs 43.48% between two groups, P<0.05. The most common olanzapine-related side-effection is somnolence and weakness.Conclusion: The 5mg olanzapine based triplet antiemetic regimen is effective and safety in the prevention carboplatin induced nausea and vomiting especially in the control of the nausea. Name of the registry: ChiCTR2000040566Trial registration number: ChiCTR2000040566Date of registration(retrospectively registered): 2th-12-2020URL of trial registry record:https://www.chictr.org.cn/listbycreater.aspx

Factors Associated With Chemotherapy-Induced Vomiting Control in Pediatric Patients Receiving Moderately or Highly Emetogenic Chemotherapy: A Pooled Analysis

PURPOSE To identify factors associated with chemotherapy-induced vomiting (CIV) control in pediatric patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). MATERIALS AND METHODS An individual, patient‐level, pooled analysis was performed using data from five clinical trials of aprepitant or fosaprepitant in pediatric patients receiving HEC or MEC. The proportion of individuals who experienced no vomiting (complete CIV control) during the phase of interest was the primary study end point. The association of acute-phase complete CIV control (from first chemotherapy dose to 24 hours after the last chemotherapy dose of the chemotherapy block) with age, sex, race, cancer type, acute-phase duration, and antiemetic regimen was examined. Association of the same factors and acute-phase complete CIV control with complete CIV control in the delayed phase (end of acute phase until ≤ 96 hours later) was examined. RESULTS A total of 735 patients (mean age, 8.9 years; range, 0.3 to 17.9 years) were included in the acute-phase analysis. Acute-phase complete CIV control was less likely in older patients (relative risk [RR], 0.97 per year; 95% CI, 0.96 to 0.98 per year) and longer acute-phase duration (RR, 0.89 per day; 95% CI, 0.84 to 0.94 per day). Receipt of ondansetron plus aprepitant or fosaprepitant was associated with a higher likelihood of acute-phase complete CIV control versus ondansetron alone (RR, 1.28; 95% CI, 1.09 to 1.50). Delayed-phase complete CIV control was more likely in patients with acute-phase complete CIV control (RR, 1.19; 95% CI, 1.06 to 1.34) and in those who received aprepitant or fosaprepitant. CONCLUSION Younger age, shorter acute-phase duration, and antiemetic regimen were associated with acute-phase complete CIV control in pediatric patients receiving HEC or MEC. Acute-phase complete CIV control and antiemetic regimen were associated with delayed-phase complete CIV control.