Phase I radioimmunotherapy trial with iodine-131--labeled humanized MN-14 anti-carcinoembryonic antigen monoclonal antibody in patients with metastatic gastrointestinal and colorectal cancer

Clin Colorectal Cancer. 2002 May;2(1):31-42. doi: 10.3816/CCC.2002.n.009.

Abstract

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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / radiotherapy*
  • Adenocarcinoma / secondary*
  • Adult
  • Aged
  • Antibodies, Monoclonal* / administration & dosage
  • Antibodies, Monoclonal* / adverse effects
  • Antibodies, Monoclonal* / pharmacokinetics
  • Antibodies, Monoclonal, Humanized
  • Carcinoembryonic Antigen / immunology*
  • Colorectal Neoplasms / pathology
  • Confidence Intervals
  • Female
  • Gastrointestinal Neoplasms* / pathology
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / pathology
  • Radioimmunotherapy*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Carcinoembryonic Antigen
  • labetuzumab