A phase I antiemetic study of MDL 73,147EF, a novel 5-hydroxytryptamine antagonist in cancer patients receiving emetogenic chemotherapy.
BACKGROUND
We conducted a phase I study with MDL 73,147EF, a new 5 hydroxytryptamine 3 (5-HT3) receptor antagonist, in 25 patients requiring emetogenic chemotherapy.


METHODS
5 groups of 5 patients received rising unit doses of MDL 73,147EF (10 to 50 mg) intravenously before chemotherapy, with two additional doses per day if needed. Nausea was assessed by a patient-completed visual analogue scale and episodes of vomiting were recorded by an independent observer.


RESULTS
42% of the patients were complete or major responders on day one. Five patients were given other rescue antiemetic therapy. Adverse effects included headache (16%) diarrhea (8%) and other minor events. The best results were obtained with the 30, 40 and 50 mg doses.


CONCLUSIONS
MDL 73,147EF is a well-tolerated and probably effective antiemetic agent which requires further evaluation in randomised controlled clinical studies.
Merrouche
Y
Y
Clinical Pharmacology Unit, Centre Léon Bérard, Lyon, France.
Catimel
G
G
Rebattu
P
P
Dumortier
A
A
Guastalla
J P
JP
O'Grady
P
P
Clavel
M
M
D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy*; D009369:Neoplasms / Q000188:drug therapy*; D011807:Quinolizines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy*
D000932:Antiemetics; D000970:Antineoplastic Agents; D007211:Indoles; D011807:Quinolizines; D012702:Serotonin Antagonists; C060344:dolasetron