Feasibility and pharmacokinetics of intraperitoneal suramin in advanced malignancy.
OBJECTIVE
Bioactive lipids have been causally linked to intraabdominal malignancies such as ovarian cancer. In advanced tumors confined to the peritoneal cavity. inhibition of lipid growth factors present in ascites might induce tumor remissions. The systemic toxicity of the growth factor inhibitor suramin has so far hampered its use in standard oncologic practice, but this could be alleviated by intraperitoneal administration. In this study the feasibility, toxicity and pharmacokinetics of intraperitoneal suramin administration are described.


METHODS
Patients with histologically verified cancer confined to the abdominal cavity, for which no effective therapy was available, were treated with intraperitoneal suramin through a Tenckhoff catheter. Patients with ascites were treated with low-volume continuous i.p. infusions of 500 mg/24 h, and patients without ascites were treated with intermittent large-volume i.p. infusions of 1000 mg three times a week. Regular pharmacokinetic sampling of plasma and ascites fluid was carried out. Patients were treated for 6 weeks or until development of progressive disease or until plasma suramin levels exceeded 250 mg/l.


RESULTS
Nine patients were treated in ten periods, three with intermittent i.p. suramin, and seven with continuous i.p. suramin, for a median of 28.5 days (16-42 days), with a median suramin dose of 12 g (range 9 21 g ). Treatment was discontinued because of high systemic suramin levels in three patients (all in the intermittent schedule), progressive disease (five patients) or completion of planned treatment (one patient). Toxicity was mild, without any of the systemic side effects commonly associated with suramin. Intraperitoneal suramin levels were consistently higher than plasma levels in all patients, but this effect was most marked in the continuous infusion schedule.


CONCLUSIONS
Intraperitoneal suramin infusion in patients with advanced peritoneal cancers is feasible and well-tolerated. Continuous low volume i.p. infusion in patients with ascites confers the largest pharmacokinetic advantage.
Department of Medical Oncology, Antoni van Leeuwenhoekhuis, The Netherlands Cancer Institute, Amsterdam. a.m.westermann@amc.uva.nl
A M
AM
Westermann
R
R
Dubbelman
J P
JP
Baars
W H
WH
Moolenaar
J H
JH
Beijnen
S
S
Rodenhuis
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000378:metabolism; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000378:metabolism; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D013498:Suramin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D008246:Lysophospholipids; D013498:Suramin