Pharmacokinetics and toxicity of an yttrium-90-CITC-DTPA-HMFG1 radioimmunoconjugate for intraperitoneal radioimmunotherapy of ovarian cancer

Cancer. 1994 Feb 1;73(3 Suppl):1067-75. doi: 10.1002/1097-0142(19940201)73:3+<1067::aid-cncr2820731346>3.0.co;2-#.

Abstract

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, 90Y-CITC-DTPA-HMFG1, instilled in the peritoneal cavity after second-look laparoscopy. Activity was increased in a stepwise fashion.

Results: Following the intraperitoneal administration of 90Y-CITC-DTPA-HMFG1, levels of the radioimmunoconjugate in the blood increased, reaching a peak of about 30% of injected activity at around 54 hours posttreatment. 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/m2. A type III immunologic response was observed in a number of patients.

Conclusions: A dose of 18.5 mCi/m2 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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / therapeutic use*
  • Brachytherapy*
  • Female
  • Humans
  • Mice / immunology
  • Middle Aged
  • Mucins / immunology
  • Ovarian Neoplasms / radiotherapy*
  • Radioimmunotherapy* / adverse effects
  • Yttrium Radioisotopes / administration & dosage
  • Yttrium Radioisotopes / pharmacokinetics
  • Yttrium Radioisotopes / therapeutic use*
  • Yttrium Radioisotopes / toxicity

Substances

  • Antibodies, Monoclonal
  • Mucins
  • Yttrium Radioisotopes