Intraperitoneally administered 90Y-labelled monoclonal antibodies as a third line of treatment in ovarian cancer. A phase 1-2 trial: problems encountered and possible solutions.
A phase 1-2 trial of 90Y-labelled monoclonal antibody, HMFG1 administered intraperitoneally to 30 patients with ovarian carcinoma is presented. The problems encountered with myelotoxicity are described, and the steps which have so far been taken to overcome this and to increase the dose of 90Y to an estimated tumouricidal level. Bone deposition of free 90Y limits the dose which can be administered without severe bone marrow toxicity. The intravenous use of a chelating agent, Ledclair (EDTA) has allowed the dose to be increased from 18 to 30 mCi without causing severe myelotoxicity. 90Y-DTPA MAb is an unstable immunoconjugate in vivo and in vitro. The use of a more stable linkage such as a macrocycle should enable the administered dose to be increased without increasing the amount of free 90Y which becomes available to be deposited in bone. This would be expected to reduce toxicity and increase therapeutic efficacy.
Hird
V
V
ICRF Oncology Group, Hammersmith Hospital, London, UK.
Stewart
J S
JS
Snook
D
D
Dhokia
B
B
Coulter
C
C
Lambert
H E
HE
Mason
W P
WP
Soutter
W P
WP
Epenetos
A A
AA
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001853:Bone Marrow / Q000528:radiation effects; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D010051:Ovarian Neoplasms / Q000532:radiotherapy*; D015021:Yttrium Radioisotopes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D015021:Yttrium Radioisotopes