A randomized trial of paracentesis plus intraperitoneal tumor necrosis factor-alpha versus paracentesis alone in patients with symptomatic ascites from recurrent ovarian carcinoma.
OBJECTIVE
Previous phase I and II studies of intraperitoneal recombinant human tumor necrosis factor-alpha (rhTNF-alpha) suggested a high degree of efficacy in reducing or eliminating ascitic fluid. To more accurately determine the efficacy of this agent, the role of paracentesis versus paracentesis plus intraperitoneal rhTNF-alpha was studied in a randomized trial.


METHODS
Thirty-nine patients with symptomatic ascites with a volume of > 1000 ml from recurrent epithelial ovarian carcinoma or primary peritoneal carcinoma, which was refractory to standard therapy, were randomized either to receive 0.06 mg/m2 rhTNF-alpha (Knoll, Canada) (the dose determined optimal from phase I and II studies) intraperitoneally after drainage of fluid or to receive drainage alone. A maximum of three treatments were given at weekly intervals. Eighteen patients were randomized to receive rhTNF-alpha.


RESULTS
None of 18 evaluable rhTNF-alpha patients had either a complete response (CR) (no clinical evidence of ascites and < 400 ml of fluid on ultrasound) or a partial response (PR) (asymptomatic ascites and < or = 1000 ml of fluid ultrasound). There were no CRs or PRs in the 17 evaluable patients who received drainage alone. The intraperitoneal infusion of rhTNF-alpha was generally well tolerated. Moderate to severe toxicity consisted of pain/discomfort in 42.1%, fever/chills in 36.9%, nausea/vomiting in 10.5%, edema in 10.5%, and hypotension in 5.3% of patients receiving rhTNF-alpha.


CONCLUSIONS
rhTNF-alpha, as given in this study, was not effective in preventing recurrence of ascites in this patient population.
Hirte
H W
HW
Ontario Cancer Treatment and Research Foundation, Hamilton Regional Cancer Centre, Canada.
Miller
D
D
Tonkin
K
K
Findlay
B
B
Capstick
V
V
Murphy
J
J
Buckman
R
R
Carmichael
J
J
Levine
M
M
Hill
W
W
D001201:Ascites / Q000209:etiology / Q000628:therapy*; D002985:Clinical Protocols; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000150:complications*; D019152:Paracentesis; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
D014409:Tumor Necrosis Factor-alpha