Phase I/II study of iodine 131-labeled monoclonal antibody A33 in patients with advanced colon cancer Journal Article


Authors: Welt, S.; Divgi, C. R.; Kemeny, N.; Finn, R. D.; Scott, A. M.; Graham, M.; St. Germain, J.; Richards, E. C.; Larson, S. M.; Oettgen, H. F.; Old, L. J.
Article Title: Phase I/II study of iodine 131-labeled monoclonal antibody A33 in patients with advanced colon cancer
Abstract: Purpose: A phase I/II study was designed to determine the maximum- tolerated dose (MTD) of iodine 131-labeled monoclonal antibody (mAb) A33 (131I-mAb A33) administered intravenously, its limiting organ toxicity, and its radioisotope retention in tumors, and to develop preliminary evidence of antitumor activity. Patients and Methods: Patients (N = 23) with colorectal cancer who had failed to respond to conventional chemotherapy but had not received prior radiotherapy were treated with escalating doses of 131I-mAb A33. Three or more patients were entered at each dose level, starting at 30 mCi/m2, with increments of 15 mCi/m2 to a maximal dose of 90 mCi/m2. Radiolabeling was performed to maintain a specific activity of 30 mCi/m2/4 mg mAb A33 (projected maximum, 15 mCi/mg). Patients were under strict isolation precautions until whole-body radiation levels decreased to less than 5 mrem/h at 1 m. Serial radioimmunoscintigrams were performed in some cases for up to 3 weeks after 131I-mAb A33 administration. Results: All 20 patients with radiologic evidence of disease showed localization of radioisotope to sites of disease. Two patients with elevated carcinoembryonic antigen (CEA) levels and negative radiologic tests did not have positive antibody scans. One patient with a small-bowel cancer also had a negative antibody scan. The major toxicity was hematologic and was more pronounced in patients with compromised bone marrow due to prior chemotherapy. Of five patients who received 78 to 84 mCi/m2 131I-mAb A33, one had grade 3 and one grade 4 toxicity; of six patients treated with 86 to 94 mCi/m2 131I- mAb A33, two had grade 4 and one grade 1 toxicity. The MTD was determined to be 75 mCi/m2 in these heavily pretreated patients. Although the isotope showed variable uptake in the normal bowel, gastrointestinal symptoms were mild (n = 8) or absent. No major responses were observed; however, three patients had evidence of mixed responses, and CEA levels decreased in two patients without clinical or radiologic measurable disease. Immunoreactivity of radiolabeled mAb A33 decreased at the highest dose levels in preparations in which specific activity exceeded 18 mCi/mg. Conclusion: The A33 antigen appears to be a promising target for radioimmunotherapy of colon cancer. The modest antitumor activity of 131I-mAb A33 in heavily pretreated patients is encouraging because of its lack of toxicity in the bowel, the only antigen-positive normal tissue.
Keywords: adult; clinical article; aged; clinical trial; advanced cancer; drug targeting; cancer radiotherapy; phase 2 clinical trial; blood toxicity; carcinoembryonic antigen; monoclonal antibody; antigen; iodine 131; colon cancer; diagnosis; drug clearance; phase 1 clinical trial; radioimmunotherapy; intravenous drug administration; immunoscintigraphy; human; male; female; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 12
Issue: 8
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 1994-08-01
Start Page: 1561
End Page: 1571
Language: English
DOI: 10.1200/jco.1994.12.8.1561
PROVIDER: scopus
PUBMED: 8040668
DOI/URL:
Notes: Article -- Source: Scopus
Altmetric Score
MSK Authors
  1. Chaitanya Divgi
    127 Divgi
  2. Ronald D Finn
    252 Finn
  3. Steven M Larson
    779 Larson
  4. Herbert F Oettgen
    10 Oettgen
  5. Lloyd J Old
    386 Old
  6. Nancy Kemeny
    358 Kemeny
  7. Martin C Graham
    29 Graham
  8. Sydney   Welt
    57 Welt