Intraperitoneal lymphokine-activated killer-cell and interleukin-2 therapy for malignancies limited to the peritoneal cavity.
Autologous lymphokine-activated killer (LAK) cells and recombinant human interleukin-2 (rIL-2) were administered intraperitoneally (IP) to 24 patients with malignancies limited to the peritoneal space. Ten patients had ovarian cancer, 12 had colorectal cancer, and one patient each had endometrial carcinoma and primary small-bowel adenocarcinoma. All ovarian cancer patients, three of twelve colorectal cancer patients, and one patient with endometrial carcinoma had received prior therapy. Patients received IL-2 100,000 U/kg every 8 hours intravenously (IV) for 3 days, and 2 days later underwent daily leukapheresis for 5 days. LAK cells were generated in vitro by incubating the peripheral blood mononuclear cells in IL-2 for 7 days and were then administered IP daily for 5 days through a Tenckhoff catheter (Davol, Inc, Cranston, RI) together with IL-2 25,000 U/kg IP every 8 hours. All but one patient completed at least one cycle of therapy. Toxic side effects included minor to moderate hypotension, fever, chills, rash, nausea, vomiting, abdominal pain and distension, diarrhea, oliguria, fluid retention, thrombocytopenia, and minor elevations of liver function tests; all of these rapidly improved after discontinuation of IL-2. One patient had a grand mal seizure, and one suffered a colonic perforation; these were felt to be treatment-related. IP fibrosis developed in 14 patients and limited repeated cyclic administration of this therapy in five patients. Two of 10 (20%) ovarian cancer patients and five of 12 (42%) colorectal cancer patients had laparoscopy- or laparotomy-documented partial responses. We conclude that LAK cells and rIL-2 can be administered IP to cancer patients, resulting in moderate to severe short-term toxicity and modest therapeutic efficacy. Further investigation of this form of adoptive immunotherapy modified to address the problem of IP fibrosis and with lower IP IL-2 doses is justified by these initial results.
Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
R G
RG
Steis
W J
WJ
Urba
L A
LA
VanderMolen
M A
MA
Bookman
J W
JW
Smith
J W
JW
Clark
R L
RL
Miller
E D
ED
Crum
S K
SK
Beckner
J E
JE
McKnight
D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000628:therapy; D005069:Evaluation Studies as Topic; D005260:Female; D005355:Fibrosis; D006801:Humans; D016219:Immunotherapy, Adoptive; D007263:Infusions, Parenteral; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015979:Killer Cells, Lymphokine-Activated / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000628:therapy; D010529:Peritoneal Cavity / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012074:Remission Induction; D014594:Uterine Neoplasms / Q000628:therapy
D007376:Interleukin-2; D011994:Recombinant Proteins