Prospects of radioimmunotherapy in epithelial ovarian cancer: results with iodine-131-labeled murine and humanized MN-14 anti-carcinoembryonic antigen monoclonal antibodies.
OBJECTIVE
Epithelial ovarian cancer (EOC) is known to produce carcinoembryonic antigen (CEA), and the plasma CEA level is frequently elevated in patients with advanced stage and bulk of tumor. This study reports the results of a phase I therapy trial with intravenously administered 131I-MN-14 anti-CEA monoclonal antibody (MAb) in patients with EOC.


METHODS
Fourteen patients with advanced refractory EOC were given escalating intravenous doses (two received 30 mCi/m2, six 40 mCi/m2, and six 50 mCi/m2) of 131I-MN-14 IgG. All patients received a diagnostic study with 8 mCi (0.6 mg) of 131I-MN-14 IgG 1 week prior to their therapy infusion. Tumor targeting was assessed by external scintigraphy, toxicity according to the Radiation Therapy Oncology Group criteria, and therapy responses by CT and serum CA-125.


RESULTS
The MAb scan was positive in all 14 treated patients. Myelosuppression was the only observed treatment-related toxicity. Dose-limiting toxicity, defined as grade 4 leukopenia or thrombocytopenia of any duration, or grade 3 leukopenia or thrombocytopenia of > 2 weeks, was not seen at the 30 or 40 mCi/m2 dose levels. However, 2 of 6 patients treated at 50 mCi/m2 had a grade 4 thrombocytopenia or a grade 3 thrombocytopenia lasting 18 days. Of the 14 patients, 1 with diffuse peritoneal implants of < or = 2 cm had a complete clinical remission by CT and CA-125 for 8 months, following an initial partial remission for 10 months, both at the 40 mCi/m2 dose level. Another patient had a mixed response for 1 month.


CONCLUSIONS
MN-14 anti-CEA MAb is a suitable agent for tumor targeting and may have a therapeutic potential in patients with chemotherapy-refractive EOC, especially those with minimal disease.
Juweid
M
M
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, New Jersey 07109, USA.
Swayne
L C
LC
Sharkey
R M
RM
Dunn
R
R
Rubin
A D
AD
Herskovic
T
T
Goldenberg
D M
DM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002277:Carcinoma / Q000532:radiotherapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007457:Iodine Radioisotopes; D051379:Mice; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000532:radiotherapy*; D016499:Radioimmunotherapy; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes; C110010:labetuzumab