PMID- 2045866 OWN - NLM STAT- MEDLINE DCOM- 19910718 LR - 20170210 IS - 0732-183X (Print) IS - 0732-183X (Linking) VI - 9 IP - 7 DP - 1991 Jul TI - Phase I study of liposomal MTP-PE-activated autologous monocytes administered intraperitoneally to patients with peritoneal carcinomatosis. PG - 1251-60 AB - 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. FAU - Faradji, A AU - Faradji A AD - Department of Medical Hematology and Oncology, University Hospital Hautepierre, Strasbourg, France. FAU - Bohbot, A AU - Bohbot A FAU - Frost, H AU - Frost H FAU - Schmitt-Goguel, M AU - Schmitt-Goguel M FAU - Siffert, J C AU - Siffert JC FAU - Dufour, P AU - Dufour P FAU - Eber, M AU - Eber M FAU - Lallot, C AU - Lallot C FAU - Wiesel, M L AU - Wiesel ML FAU - Bergerat, J P AU - Bergerat JP AU - et al. LA - eng PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Indium Radioisotopes) RN - 0 (Liposomes) RN - 0 (Monokines) SB - IM MH - Aged MH - Analysis of Variance MH - Blood Cell Count MH - Carcinoma/blood/etiology/pathology/*therapy MH - Drug Evaluation MH - Female MH - Humans MH - Indium Radioisotopes MH - Infusions, Parenteral/instrumentation MH - Liposomes MH - Male MH - Middle Aged MH - *Monocytes, Activated Killer MH - Monokines/blood MH - Peritoneal Neoplasms/blood/etiology/pathology/*therapy MH - Regression Analysis MH - Time Factors EDAT- 1991/07/01 00:00 MHDA- 1991/07/01 00:01 CRDT- 1991/07/01 00:00 PHST- 1991/07/01 00:00 [pubmed] PHST- 1991/07/01 00:01 [medline] PHST- 1991/07/01 00:00 [entrez] AID - 10.1200/JCO.1991.9.7.1251 [doi] PST - ppublish SO - J Clin Oncol. 1991 Jul;9(7):1251-60. doi: 10.1200/JCO.1991.9.7.1251.