Abstract |
From March 1987 to March 1988, a phase I to II study was carried out in 25 patients with ovarian cancer. They received escalating doses of intraperitoneally (IP) administered yttrium-90 (Y-90)-labeled monoclonal antibody, HMFG1, against a tumor cell-surface antigen. Myelosuppression prevented an escalation of the administered Y-90 activity above 25 mCi. Y-90-labeled antibody was absorbed from the peritoneal cavity into the circulation. Maximum blood Y-90 activity was observed 40 hours after the IP injection with a mean of 21% of the injected activity (range, 14.2% to 26.4%) in the circulation. The radiation dose the bone marrow received from circulating Y-90-labeled antibody (the blood radiation dose) was calculated by applying the Medical Internal Radiation Dose (MIRD) formulation to the measured Y-90 activity in patients blood. Myelosuppression occurred following calculated blood radiation doses to bone marrow of only 10 to 30 cGy. The excessive myelosuppression following such modest radiation doses from circulating Y-90-labeled antibody could be explained by the uptake of Y-90 by bone. In an attempt to reduce bone absorption of Y-90, seven patients received an intravenous (IV) infusion of EDTA (Sinclair Pharmaceuticals Ltd, Godalming, United Kingdom). This increased the urinary excretion of Y-90 from a mean of 11.1% to 32.3% of the injected activity (P = .0001). Fourteen patients had assessable tumor at laparoscopy. Tumor regression was observed in one patient, and palliation of ascites in a further patient.
|
Authors | J S Stewart, V Hird, D Snook, B Dhokia, G Sivolapenko, G Hooker, J T Papadimitriou, G Rowlinson, M Sullivan, H E Lambert |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 8
Issue 12
Pg. 1941-50
(Dec 1990)
ISSN: 0732-183X [Print] United States |
PMID | 2230887
(Publication Type: Clinical Trial, Journal Article)
|
Chemical References |
- Antibodies, Monoclonal
- Immunotoxins
- Yttrium Radioisotopes
|
Topics |
- Adult
- Aged
- Antibodies, Monoclonal
(administration & dosage, pharmacokinetics, therapeutic use)
- Bone Marrow
(radiation effects)
- Female
- Humans
- Immunotoxins
(administration & dosage, pharmacokinetics, therapeutic use)
- Injections, Intraperitoneal
- Middle Aged
- Ovarian Neoplasms
(drug therapy, metabolism)
- Radiotherapy Dosage
- Remission Induction
- Yttrium Radioisotopes
(administration & dosage, pharmacokinetics, therapeutic use)
|