Intraoperative chemotherapy with cisplatin and epinephrine after cytoreductive surgery in patients with recurrent ovarian cancer: a phase I study.
BACKGROUND
Intraperitoneal (i.p.) epinephrine was shown to increase the accumulation of i.p. cisplatin in tumours, and thus its antitumour effect in a model of peritoneal carcinomatosis in rats.


METHODS
To determine the tolerance to i.p. epinephrine with cisplatin, 18 patients with recurrent ovarian carcinoma were intraoperatively treated in this phase 1 study. After maximal cytoreductive surgery, the peritoneal cavity was filled twice for 1 h with 30 mg/l of cisplatin and increasing concentrations of epinephrine (0, 1, 2, 3 mg/l) in 3 l of saline solution at 37 degrees C.


RESULTS
No deaths occurred. Three patients were treated at each of the 0, 1 and 2 mg/l epinephrine levels without adverse events. Two of the three patients who received 3 mg/l epinephrine experienced cardiac intolerance. Six additional patients received 2 mg/l of epinephrine without toxicity. A relationship between the serum concentration of epinephrine and occurrence of cardiac toxicity was established. A 60% decrease in serum area under the curve of platinum was calculated in patients receiving i.p. epinephrine compared with i.p. cisplatin alone. Renal toxicity from cisplatin was not increased by epinephrine. No haematological or neurological toxicity was recorded. The other grade 3-4 adverse events [thromboembolism (5), peritonitis (1), abdominal bleeding (1), bowel fistula (1)] occurred as often as usually reported for this heavy surgical procedure.


CONCLUSIONS
The combination of i.p. epinephrine with cisplatin as intraoperative chemotherapy after optimal cytoreductive surgery is feasible. The recommended concentration for further studies is 2 mg/l for i.p. epinephrine.
Guardiola
Emmanuel
E
Department of Medical Oncology, University Hospital Jean Minjoz, France.
Chauffert
Bruno
B
Delroeux
Delphine
D
Royer
Bernard
B
Heyd
Bruno
B
Combe
Marielle
M
Benoit
Laurent
L
Causeret
Sylvain
S
Demarchi
Martin
M
Magnin
Guy
G
Mayer
Françoise
F
Tixier
Hervé
H
Pivot
Xavier
X
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D004837:Epinephrine / Q000009:adverse effects / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D005602:France; D006335:Heart Injuries / Q000139:chemically induced; D006801:Humans; D007274:Injections, Intraperitoneal; D007430:Intraoperative Care; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000601:surgery; D016896:Treatment Outcome
D002945:Cisplatin; D004837:Epinephrine