One-Day Versus Three-Day Dexamethasone in Combination with Palonosetron for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Systematic Review and Individual Patient Data-Based Meta-Analysis

Abstract

Background. A dexamethasone-sparing regimen consisting of palonosetron plus 1-day dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) has been studied previously. Here, we evaluate the noninferiority of the dexamethasone-sparing regimen in overall antiemetic control using a meta-analysis based on individual patient data (IPD). Materials and Methods. We conducted a systematic review for randomized trials reporting CINV outcomes for the comparison of palonosetron plus 1-day dexamethasone (d1 arm) versus the same regimen followed by dexamethasone on days 2-3 after chemotherapy (d3 arm) in chemotherapynaïve adult patients undergoing either moderately emetogenic chemotherapy (MEC) or anthracycline plus cyclophosphamide (AC)-containing chemotherapy. PubMed and MEDLINE were searched electronically. A manual search was also conducted. The primary endpoint was complete response (CR; no emesis and no rescue medication) in the overall 5-day study period. The noninferiority margin was set at −8.0% (d1 arm−d3 arm). Results. Five studies (n = 1,194) were eligible for analysis and all IPD was collected. In the overall study period, the d1 arm showed noninferiority to the d3 arm for CR as well as complete control (pooled risk difference in CR rate − 1.5%, 95% confidence interval [CI] −7.1 to 4.0%, I 2 = 0%; in complete control rate − 2.4%, 95% CI −7.7 to 2.9%, I 2 = 0%). There was no significant interaction between dexamethasone regimen and risk factors (type of chemotherapy, sex, age, and alcohol consumption). Conclusion. This IPD meta-analysis indicates that the dexamethasone-sparing regimen is not associated with a significant loss in overall antiemetic control in patients undergoing MEC or AC-containing chemotherapy, irrespective of known risk factors for CINV. The Oncologist 2019;24:1593-1600 Implications for Practice: Although dexamethasone in combination with other antiemetic agents has been used to prevent chemotherapy-induced nausea and vomiting (CINV), it is of clinical importance to minimize total dose of dexamethasone in patients undergoing multiple cycles of emetogenic chemotherapy. This individual-patient-data meta-analysis from five Symptom Management and Supportive Care randomized controlled trials (1,194 patients) demonstrated a noninferiority of the dexamethasone-sparing regimen for complete response and complete control of CINV. The outcomes were comparable across patients with different characteristics. These findings thus help physicians minimize use of the steroid and further reduce the burden of dexamethasone-related side effects in patients undergoing multiple consecutive courses of emetogenic chemotherapy.Okada, Oba, Furukawa et al. 1597 b d3 arm: palonosetron plus 3-day dexamethasone.

Identification of optimal contemporary antiemetic prophylaxis for doxorubicin-cyclophosphamide chemotherapy in Chinese cancer patients: post-hoc analysis of 3 prospective studies

“…In addition, in a phase III trial where patients undergoing highly emetogenic chemotherapy were given an NK1RA (aprepitant or fosaprepitant) and palonosetron and randomized to 1-day or 3-day dexamethasone, non-inferiority in CR percentages for the overall time frame was reported 25 . The current results are further supported by a recent meta-analysis that included 5 studies testing palonosetron and dexamethasone on patients undertaking AC-based or non-AC moderately emetogenic chemotherapy 26 .…”

5HT3RA plus dexamethasone plus aprepitant for controlling delayed chemotherapy‐induced nausea and vomiting in colorectal cancer

“…A DEX-sparing strategy of antiemetic prophylaxis consisting of PALO + 1-day DEX for the prevention of CINV has been studied previously. 18,29,30 A meta-analysis 31 indicated that a DEX-sparing antiemetic regimen was not associated 16,21,[33][34][35] In the present study, a drinking habit and history of motion sickness were identified as patient-related risk factors for delayed nausea. Female sex was identified as a patient-related risk factor for delayed vomiting.…”

Impact of dexamethasone-sparing regimens on delayed nausea caused by moderately or highly emetogenic chemotherapy: a meta-analysis of randomised evidence

“…These results are very reassuring on the anti-emetic efficacy of DEX-sparing regimens, having been obtained in a heterogeneous population including breast cancer patients, a particularly high-risk subgroup for nausea caused by AC [26]. Overall, the results of the current meta-analysis constitute new and clinically relevant information that adds to the findings from a recent meta-analysis of individual patient data (IPD) showing that the DEX-sparing strategy is not associated with a significant loss in anti-emetic control during the overall period, irrespective of known risk factors for CINV [27]. It also should be noted that the IPD meta-analysis included patients from five studies of the DEX-sparing strategy, while there was only the small-size study by Kosaka et al [25] which included patients undergoing AC who received also an NK-1RA as recommended by current guidelines [4, 5].…”