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Pharmacokinetics and toxicity of an yttrium‐90‐citc‐dtpa‐hmfg1 radioimmunoconjugate for intraperitoneal radioimmunotherapy of ovarian cancer
Author(s) -
Maraveyas Anthony,
Snook Deborah,
Hird Vicky,
Kosmas Christos,
Meares Claude F.,
Lambert Hanna E.,
Epenetos Agamem A.
Publication year - 1994
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19940201)73:3+<1067::aid-cncr2820731346>3.0.co;2-#
Subject(s) - medicine , radioimmunotherapy , toxicity , ovarian cancer , bone marrow , pharmacokinetics , peritoneal cavity , monoclonal antibody , gastroenterology , pharmacology , cancer , pathology , antibody , immunology , surgery
Background . The intracavitary route for the administration of monoclonal antibodies is used in a variety of locally spreading cancers. The authors have been treating patients with ovarian cancer in Phase I and II studies assessing toxicity and response to improved radioimmunoconjugates. Methods . Nineteen patients, 34–65 years of age, were treated with a new radioimmunoconjugate, 90 Y‐CITC‐DTPA‐HMFG1, instilled in the peritoneal cavity after second‐look laparoscopy. Activity was increased in a step‐wise fashion. Results . Following the intraperitoneal administration of 90 Y‐CITC‐DTPA‐HMFG1, levels of the radioimmunoconjugate in the blood increased, reaching a peak of about 30% of injected activity at around 54 hours post‐treatment. Approximately 18% of the radiolabel was excreted in the urine within 96 hours. Bone‐marrow toxicity was the dose‐limiting factor. Grade III platelet and granulocyte toxicity was observed at 19.3 mCi/m 2 . A type III immunologic response was observed in a number of patients. Conclusions . A dose of 18.5 mCi/m 2 for subsequent treatments is recommended, based on a linear correlation of activity dose‐to‐body surface area. The clinical profile of a mild to moderate hypersensitivity syndrome is presented and hypotheses regarding its etiology are suggested. Cancer 1994; 73:1067–75.