Pharmacokinetics and toxicity of an yttrium-90-CITC-DTPA-HMFG1 radioimmunoconjugate for intraperitoneal radioimmunotherapy of ovarian cancer.
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.
Maraveyas
A
A
Department of Clinical Oncology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
Snook
D
D
Hird
V
V
Kosmas
C
C
Meares
C F
CF
Lambert
H E
HE
Epenetos
A A
AA
D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000627:therapeutic use*; D001918:Brachytherapy; D005260:Female; D006801:Humans; D051379:Mice / Q000276:immunology; D008875:Middle Aged; D009077:Mucins / Q000276:immunology; D010051:Ovarian Neoplasms / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000009:adverse effects; D015021:Yttrium Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity
D000911:Antibodies, Monoclonal; D009077:Mucins; D015021:Yttrium Radioisotopes