Phase I radioimmunotherapy trial with iodine-131--labeled humanized MN-14 anti-carcinoembryonic antigen monoclonal antibody in patients with metastatic gastrointestinal and colorectal cancer.
This trial was conducted to determine the pharmacokinetics, dosimetry, dose-limiting toxicity, and the maximum tolerated dose of iodine-131 humanized MN-14 immunoglobulin G (131I-hMN-14 IgG), a humanized complementary-determining region-grafted anti-carcinoembryonic antigen monoclonal antibody, in metastatic gastrointestinal and colorectal cancer patients. Patients were divided into 2 groups: group A consisted of patients who had prior external beam radiation therapy (n = 8), and group B included patients who had received standard chemotherapy (n = 13). All patients received a diagnostic infusion of 131I-hMN-14 IgG (approximately 8.0 mCi, 15 mg/m2) to study the pharmacokinetics, biodistribution, and dosimetry. One week later, 17 of 21 patients received infusional therapy of escalating radioactive doses of 131I-hMN-14 IgG. Blood pharmacokinetics and quantitative imaging were performed again after the therapeutic dose. Radiation-absorbed doses to normal organs and tumors were determined by MIRDOSE-3 algorithms. The primary dose-limiting toxicity was hematologic toxicity at 40 mCi/m2. The blood half-life (n = 20) was identical for the diagnostic and therapy infusions. The mean red marrow dose was 2.2 +/- 2.4 cGy/mCi. The mean tumor radiation dose (n = 8) was 24.2 +/- 22.6 cGy/mCi. Tumor targeting was seen in most large metastatic lesions. No objective responses were seen in these heavily pretreated and mostly advanced patients. In conclusion, 131I-hMN-14 IgG has good targeting, good tumor to normal organs radiation absorbed ratios, and an acceptable toxicity profile in advanced metastatic gastrointestinal and colorectal cancer patients.
Hajjar
George
G
Garden State Cancer Center, 520 Belleville Ave, Belleville, NJ 07109, USA.
Sharkey
Robert M
RM
Burton
Jack
J
Zhang
Chu-Hui
CH
Yeldell
Dion
D
Matthies
Alexander
A
Alavi
Abass
A
Losman
Michele J
MJ
Brenner
Arnold
A
Goldenberg
David M
DM
D000230:Adenocarcinoma / Q000532:radiotherapy* / Q000556:secondary*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000473:pathology; D016001:Confidence Intervals; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000473:pathology; D016499:Radioimmunotherapy
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002272:Carcinoembryonic Antigen; C110010:labetuzumab