Phase I study of liposomal MTP-PE-activated autologous monocytes administered intraperitoneally to patients with peritoneal carcinomatosis.
We have conducted a phase I study with autologous monocytes activated ex vivo and administered intraperitoneally in nine patients with peritoneal carcinomatosis. Blood monocytes were collected by leukapheresis and then purified by counterflow elutriation (up to 10(9) cells, with a purity of greater than 90%). Ex vivo activation was obtained by incubating these cells with 1 micrograms liposomal MTP-PE/10(6) monocytes for 18 hours in hydrophobic culture bags at 37 degrees C in 5% carbon dioxide humidified air. The activated monocytes were then infused in the peritoneal cavity once a week for 5 consecutive weeks through an implanted peritoneal infusion system, Port-A-Cath (Pharmacia Deltec, St Paul, MN), on an intrapatient dose-escalating schedule (10(7) to 10(9) monocytes). No severe adverse reactions occurred. Toxicity was mild, the chief acute reactions being fever (27%), chills (13%), and abdominal pain (25%). None of the side effects led to dose reduction. No consistent change in hemostatic function, liver function, or renal function was observed. Significant increases in granulocyte counts, neopterine, and acute phase reactants (fibrinogen, C-reactive protein) occurred in the peripheral blood. In vitro monocyte activation was demonstrated by the relapse of procoagulant activity and monokines (interleukin-1 [IL-1], IL-6, and tumor necrosis factor-alpha [TNF alpha]) in the supernatants of cultured monocytes. Evidence for in vivo monocyte activation was provided by the increase of these monokines in the peritoneal fluids. Kinetic studies with indium-111 (111In)-labeled activated autologous monocytes in five patients suggest that these infused monocytes may remain in the peritoneal cavity for up to 7 days. This locoregional immunotherapeutic approach seems to be encouraging in view of adjuvant therapeutic modality in ovarian cancer patients with minimal residual intraabdominal disease following second-look laparotomy.
Faradji
A
A
Department of Medical Hematology and Oncology, University Hospital Hautepierre, Strasbourg, France.
Bohbot
A
A
Frost
H
H
Schmitt-Goguel
M
M
Siffert
J C
JC
Dufour
P
P
Eber
M
M
Lallot
C
C
Wiesel
M L
ML
Bergerat
J P
JP
D000368:Aged; D000704:Analysis of Variance; D001772:Blood Cell Count; D002277:Carcinoma / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes; D007263:Infusions, Parenteral / Q000295:instrumentation; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D016260:Monocytes, Activated Killer; D015846:Monokines / Q000097:blood; D010534:Peritoneal Neoplasms / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D012044:Regression Analysis; D013997:Time Factors
D007205:Indium Radioisotopes; D008081:Liposomes; D015846:Monokines