Interaction between serotonin reuptake inhibitors, 5-HT3 antagonists, and NK1 antagonists in cancer patients receiving highly emetogenic chemotherapy: a case-control study.
BACKGROUND
Previous reports suggested that selective serotonin reuptake inhibitors (SSRI) could decrease the activity of 5-hydroxytryptamine type 3 (5-HT3) antagonists against acute chemotherapy-induced nausea and vomiting (CINV), possibly through serotonin accumulation for 5-HT3 receptors.


METHODS
Chemonaive cancer patients receiving SSRI and antiemetic agents, including the 5-HT3 antagonist ondansetron and the neurokinin 1 (NK1) antagonist aprepitant for highly emetogenic chemotherapy (etoposide-platinum), were matched to control patients for the following variables: age, gender, primary tumor, past history of gestational emesis, chronic intake of benzodiazepines and/or corticosteroids, chronic alcohol intake, and aprepitant use. The primary evaluation criterion was the occurrence of acute vomiting during the first two cycles of treatment.


RESULTS
Forty-four patients were eligible for this analysis. The proportion of patients, who experienced at least one episode of grade ≥ 1 acute vomiting in patients receiving SSRI, compared to patients who did not, was significantly higher (59.1 vs. 22.7%, respectively, p = 0.03, odds ratio 4.72, 95% confidence interval 1.13-22.88). Grade ≥ 2 acute vomiting was also significantly more frequent in patients receiving SSRI, even after the implementation of aprepitant to antiemetic prophylaxis (41.2 vs. 5.9%, p = 0.04).


CONCLUSIONS
Our findings reinforce the hypothesis that SSRI decrease the antiemetic activity of the 5-HT3 serotonin antagonist ondansetron, resulting in higher rates of acute vomiting in cancer patients despite adequate antiemetic prophylaxis. Adding the NK1 antagonist aprepitant do not counterbalance the deleterious effect of SSRI, probably due to the synergistic effects of SSRI and NK1 antagonists on serotonin transmission.
Department of Medical Oncology, Cochin Teaching Hospital, Université Paris Descartes, Sorbonne Paris Cité, AP-HP, Paris, France. olivier.mir@cch.aphp.fr
Olivier
O
Mir
Jean-Philippe
JP
Durand
Pascaline
P
Boudou-Rouquette
Julie
J
Giroux
Romain
R
Coriat
Anatole
A
Cessot
Stanislas
S
Ropert
François
F
Goldwasser
Raphaël
R
Gaillard
D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use; D000077608:Aprepitant; D016022:Case-Control Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D005047:Etoposide / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology*; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D010984:Platinum / Q000009:adverse effects; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D014839:Vomiting / Q000139:chemically induced* / Q000188:drug therapy
D000932:Antiemetics; D000972:Antineoplastic Agents, Phytogenic; D000077608:Aprepitant; D005047:Etoposide; D009025:Morpholines; D010984:Platinum; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors