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

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.

• Authors: A Maraveyas, D Snook, V Hird, C Kosmas, C F Meares, H E Lambert, A A Epenetos
• Journal: Cancer (Cancer) Vol. 73 Issue 3 Suppl Pg. 1067-75 (Feb 01 1994) ISSN: 0008-543X [Print] United States
• PMID: 8306249 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Antibodies, Monoclonal
• Mucins
• Yttrium Radioisotopes

Topics

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