Intraperitoneal yttrium-90-labeled monoclonal antibody in ovarian cancer.
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.
Stewart
J S
JS
Department of Clinical Oncology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
Hird
V
V
Snook
D
D
Dhokia
B
B
Sivolapenko
G
G
Hooker
G
G
Papadimitriou
J T
JT
Rowlinson
G
G
Sullivan
M
M
Lambert
H E
HE
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D001853:Bone Marrow / Q000528:radiation effects; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011879:Radiotherapy Dosage; D012074:Remission Induction; D015021:Yttrium Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D015021:Yttrium Radioisotopes