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

A. Maraveyas, D. Snook, V. Hird, C. Kosmas, C. F. Meares, H. E. Lambert, A. A. Epenetos

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1067-1075
Number of pages9
JournalCancer
Volume73
Issue numberSUPPL.
StatePublished - 1994

Keywords

  • ovarian cancer
  • pharmacokinetics
  • radioimmunoconjugate
  • serum sickness
  • yttrium-90

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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