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The Oncologist Dec 2019A dexamethasone-sparing regimen consisting of palonosetron plus 1-day dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) has been... (Meta-Analysis)
Meta-Analysis
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.
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 chemotherapy-naïve 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 ( = 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 = 0%; in complete control rate - 2.4%, 95% CI -7.7 to 2.9%, I = 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.
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 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.
Topics: Dexamethasone; Drug Dosage Calculations; Female; Humans; Male; Middle Aged; Nausea; Palonosetron; Vomiting
PubMed: 31217343
DOI: 10.1634/theoncologist.2019-0133 -
Supportive Care in Cancer : Official... Mar 2020Olanzapine, neurokinin-1-receptor-antagonists (NK-1-RA), and thalidomide added to palonosetron + dexamethasone (PALO-DEX) have been evaluated in separate studies as... (Meta-Analysis)
Meta-Analysis
Efficacy of olanzapine, neurokinin-1 receptor antagonists, and thalidomide in combination with palonosetron plus dexamethasone in preventing highly emetogenic chemotherapy-induced nausea and vomiting: a Bayesian network meta-analysis.
BACKGROUND
Olanzapine, neurokinin-1-receptor-antagonists (NK-1-RA), and thalidomide added to palonosetron + dexamethasone (PALO-DEX) have been evaluated in separate studies as prophylaxis for chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC). We conducted a Bayesian network meta-analysis to compare the prophylactic efficacy of these agents in combination with PALO-DEX.
METHODS
PubMed, Medline/Ovid, Embase, and Clinicaltrials.gov were searched from inception through 22 Mar 2018. Study quality was assessed using the Cochrane methodology. A Bayesian network meta-analysis using random-effects models was used to asses complete response (CR) and rate of no nausea (RNN) in acute, delayed, and overall phases and were expressed as odds ratios (OR) and 95% credible interval (95% CrI). Ranking probabilities of treatments were calculated using the surface under the cumulative ranking curve (SUCRA) to identify the probability of a given treatment as the best option against the worst option.
RESULTS
Nine RCTs involving two thousand nine hundred fifty-nine patients were included. The olanzapine-based regimen showed greater CR in the acute, delayed, and overall-phases versus the PALO-DEX regimen (OR = 3.97, 95% CrI = 1.02-19.13; OR = 5.62, 95% CrI = 1.66-28.58; OR = 4.79, 95% CrI = 1.40-24.02, respectively). Additionally, it showed greater RNN than the NK-1-RA-based and the PALO-DEX regimens in the delayed phase only (OR = 2.90, 95% CrI = 1.34-5.15; OR = 4.53, 95% CrI = 1.89-10.55, respectively). Olanzapine-, NK-1-RA-, and thalidomide-based regimens did not differ in CR in the three phases. SUCRA probabilities ranked the olanzapine-based regimen as the best option in terms of CR and RNN, while ranking the NK-1-RA-based regimens as the second best option in terms of CR throughout the three phases.
CONCLUSION
Based on the data included in the analyses, there is insufficient evidence to support adding thalidomide or NK-1-RA to PALO-DEX in preventing CINV induced by HEC. However, adding olanzapine to PALO-DEX achieves better CR and RNN. Olanzapine side-effects and the absence of direct comparisons explain why some guidelines are cautious in suggesting the use of olanzapine.
Topics: Antiemetics; Antineoplastic Agents; Bayes Theorem; Dexamethasone; Drug Therapy, Combination; Humans; Induction Chemotherapy; Nausea; Network Meta-Analysis; Neurokinin-1 Receptor Antagonists; Olanzapine; Palonosetron; Randomized Controlled Trials as Topic; Thalidomide; Vomiting
PubMed: 31823054
DOI: 10.1007/s00520-019-05210-4