ABSTRACT
Although radiation-induced mesenteritis or peritonitis can potentially exacerbate the risk of bowel obstruction, there are no data in the literature on the incidence of intestinal obstruction related to peptide receptor radionuclide therapy. Methods: The records of all patients treated with 177Lu-DOTATATE at Moffitt Cancer Center between April 2018 and October 2019 were evaluated. The number of patients who developed bowel obstruction within 3 mo of a 177Lu-DOTATATE treatment was divided by the total number of patients with preexisting peritoneal or mesenteric disease. Management strategies and outcomes were evaluated. Results: Of a total of 159 patients treated, 81 had baseline mesenteric or peritoneal disease, among whom 5 (6%) experienced at least 1 episode of bowel obstruction within 3 mo of treatment. Two of the patients underwent surgical exploration during obstruction describing a "frozen abdomen." All 5 responded at least temporarily to high-dose corticosteroid treatment and regained bowel function, but 2 patients eventually succumbed to progressive peritoneal disease. Conclusion: Peptide receptor radionuclide therapy can lead to bowel obstruction in patients with mesenteric or peritoneal disease, likely by inducing inflammation. Corticosteroids can potentially play a role in treatment and prophylaxis.
Subject(s)
Intestinal Obstruction/etiology , Mesentery/radiation effects , Peritoneal Diseases/radiotherapy , Receptors, Peptide/metabolism , Female , Humans , Male , Middle Aged , Octreotide/adverse effects , Octreotide/analogs & derivatives , Octreotide/therapeutic use , Organometallic Compounds/adverse effects , Organometallic Compounds/therapeutic use , Peritoneal Diseases/metabolism , RiskABSTRACT
The studies reported herein demonstrate the efficacy of alpha-particle-targeted radiation therapy of peritoneal disease with Herceptin as the targeting vehicle. Using the CHX-A-DTPA linker, Herceptin was radiolabeled with indium-111 and bismuth-213 with high efficiency without compromising immunoreactivity. A pilot radioimmunotherapy study treating mice bearing 5-day LS-174T (i.p.) xenografts, a low but uniform HER2 expressing, human colon carcinoma, with a single dose of (213)Bi-CHX-A"-Herceptin, proved disappointing. This defined the effect of tumor burden/size on tumor response to radioimmunotherapy with alpha-radiation. A more successful experiment with a lower tumor burden (3 days) in mice followed. A specific dose-response (P = 0.009) was observed, and although a maximum-tolerated dose was not determined, a dose of 500 to 750 muCi was selected as the operating dose for future experiments based on changes in animal weight. Median survival was increased from 20.5 days for the mock-treated mice to 43 and 59 days with 500 and 750 muCi, respectively. The therapeutic effectiveness of (213)Bi-CHX-A"-Herceptin was also evaluated in a second animal model for peritoneal disease with a human pancreatic carcinoma (Shaw). The results of this study were not as dramatic as with the former model, and higher doses were required to obtain an increase in survival of the mice (P = 0.001).
Subject(s)
Antibodies, Monoclonal/therapeutic use , Colonic Neoplasms/radiotherapy , Indium Radioisotopes/therapeutic use , Pentetic Acid/analogs & derivatives , Peritoneal Diseases/radiotherapy , Radioimmunotherapy , Receptor, ErbB-2/antagonists & inhibitors , Animals , Antibodies, Monoclonal/pharmacokinetics , Antibodies, Monoclonal, Humanized , Colonic Neoplasms/metabolism , Colonic Neoplasms/secondary , Female , Humans , Indium Radioisotopes/pharmacokinetics , Isothiocyanates/chemistry , Isothiocyanates/metabolism , Mice , Mice, Nude , Pentetic Acid/chemistry , Pentetic Acid/metabolism , Peritoneal Diseases/metabolism , Pilot Projects , Receptor, ErbB-2/metabolism , Stereoisomerism , Survival Rate , Tissue Distribution , Transplantation, Heterologous , TrastuzumabABSTRACT
Two-hundred-eighty-nine patients received treatment with chronic phosphate (32P) colloidal suspension (CPCS) 346 times since 1963. One-hundred-seventy-eight patients received 200 intraperitoneal treatments. One-hundred-fifteen patients received 144 intrapleural treatments. Six patients received both intraperitoneal and intrapleural treatments. Two patients received two intrapericardial treatments. Results of therapy were evaluated three months later and then at yearly intervals. In those patients who survived three months, the referring physician observed improvement in 85% of intraperitoneal treatment and in 75% of intrapleural treatments.
