Neurokinin-1 receptor antagonists for chemotherapy-induced nausea and vomiting: a systematic review.
BACKGROUND
The addition of neurokinin-1 receptor (NK1R) antagonists to antiemetic regimens has substantially reduced chemotherapy-induced nausea and vomiting (CINV). We sought to systematically review the overall impact of NK1R antagonists on CINV prevention.


METHODS
We systematically searched the MEDLINE, EMBASE, and CENTRAL databases, and meeting proceedings for randomized controlled trials (RCTs) that evaluated NK1R antagonists plus standard antiemetic therapy for CINV prevention. Complete response (CR) to therapy was defined as the absence of emesis and the absence of rescue therapy. The endpoints were defined as CR in the overall phase (during the first 120 hours of chemotherapy), CR in the acute phase (first 24 hours), and the delayed phase (24-120 hours) after chemotherapy, nausea, and toxicity. Subgroup analyses evaluated the type of NK1R antagonist used, the emetogenic potential of the chemotherapy regimen, and prolonged use of 5-HT3 (serotonin) receptor antagonists, a class of standard antiemetic agents. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Statistical tests for heterogeneity were one-sided; statistical tests for effect estimates and publication bias were two-sided.


RESULTS
Seventeen trials (8740 patients) were included in this analysis. NK1R antagonists increased the CR rate in the overall phase from 54% to 72% (OR = 0.51, 95% CI = 0.46 to 0.57, P < .001). CR and nausea were improved in all phases and subgroups. The expected side effects from NK1R antagonists did not statistically significantly differ from previous reports; however, this analysis suggests that the incidence of severe infection increased from 2% to 6% in the NK1R antagonist group (three RCTs with a total of 1480 patients; OR = 3.10; 95% CI = 1.69 to 5.67, P < .001).


CONCLUSIONS
NK1R antagonists increased CINV control in the acute, delayed, and overall phases. They are effective for both moderately and highly emetogenic chemotherapy regimens. Their use might be associated with increased infection rates; however, additional appraisal of specific data from RCTs is needed.
Medical Oncology Department, Gastrointestinal Oncology Division, Barretos Cancer Hospital, 520 Brasil St, Barretos, Sao Paulo 14784-011, Brazil. lucasvsantos@yahoo.com
Lucas Vieira
LV
dos Santos
Fabiano Hahn
FH
Souza
Andre Tesainer
AT
Brunetto
Andre Deeke
AD
Sasse
João Paulo
JP
da Silveira Nogueira Lima
D000932:Antiemetics / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D000077608:Aprepitant; D016001:Confidence Intervals; D006801:Humans; D007239:Infections / Q000209:etiology; D009025:Morpholines / Q000627:therapeutic use; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy; D064729:Neurokinin-1 Receptor Antagonists; D016017:Odds Ratio; D010879:Piperazines / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000627:therapeutic use; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control*; D014508:Urea
D000932:Antiemetics; D000077608:Aprepitant; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D010879:Piperazines; D010880:Piperidines; D058831:Serotonin 5-HT3 Receptor Antagonists; C531951:casopitant; D014508:Urea