High-dose therapy with iodine-131-labeled monoclonal antibody CC49 in patients with gastrointestinal cancers: A phase I trial

M. Tempero, P. Leichner, G. Dalrymple, K. Harrison, S. Augustine, J. Schlam, J. Anderson, James Lowell Wisecarver, D. Colcher

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Abstract

Purpose: A phase I trial that evaluated far extrahematopoietic toxicity was conducted with iodine- 131 (131I) labeled monoclonal antibody (MAb) CC49. Correlative studies included pharmacokinetic and biodistribution analyses, estimates of absorbed radiation dose, and measurement of human antimonoclonal antibodies (HAMA). Patients and Methods: After collection and cryopreservation of hematopoietic stem cells, 15 patients with gastrointestinal cancers were administered a tracer dose of 131I-MAb CC49. Within 5 to 6 days, 14 patients (two to three per activity level) underwent a single treatment with 131I-MAb CC49 (50, 100, 150, 200, 250, and 300 mCi/m2). Biodistribution was determined using planar and single photon emission computer tomographic (SPECT) imaging. Pharmacokinetic studies were performed by measuring radioactivity in serial blood samples. In some patients, biopsies of metastases and related normal tissues were obtained for radioactivity measurements. Radiation dosimetry/estimates were calculated using available biodistribution, pharmacokinetic, and tissue biopsy data. Toxicity was evaluated using the National Cancer Institute (NCI) Common Toxicity Criteria. Results: No dose-limiting extrahematopoietic toxicity was identified. Twelve patients experienced grade IV myelosuppression and met criteria for infusion of hematopoietic stem cells. Radioimmunolocalization was excellent. The T(1/2) for 131I-MAb CC49 after diagnostic and therapeutic administration was 39.7 ± 10.4 and 46.1 ± 10.6 hours, respectively. The percent injected dose per killigram of tumor ranged from 0.2 to 2.1. Absorbed radiation dose in metastatic tumor sites ranged from 630 to 3300 cGy. Conclusion: Although extrahematopoietic dose-limiting toxicity was neither observed or predicted, suboptimal absorbed dose estimates suggested that further escalation of 131I-MAb CC49 would not be useful. Future studies should focus on the use of radionuclides with high energy β emissions, such as yttrium90, and on strategies to optimize access of antibody to target antigens.

Original languageEnglish (US)
Pages (from-to)1518-1528
Number of pages11
JournalJournal of Clinical Oncology
Volume15
Issue number4
DOIs
StatePublished - Apr 1997

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Gastrointestinal Neoplasms
Iodine
Monoclonal Antibodies
Pharmacokinetics
Hematopoietic Stem Cells
Radioactivity
Radiation
Radiometry
Biopsy
Therapeutics
National Cancer Institute (U.S.)
Antibodies
Cryopreservation
Photons
Radioisotopes
Neoplasms
Neoplasm Metastasis
Antigens

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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High-dose therapy with iodine-131-labeled monoclonal antibody CC49 in patients with gastrointestinal cancers : A phase I trial. / Tempero, M.; Leichner, P.; Dalrymple, G.; Harrison, K.; Augustine, S.; Schlam, J.; Anderson, J.; Wisecarver, James Lowell; Colcher, D.

In: Journal of Clinical Oncology, Vol. 15, No. 4, 04.1997, p. 1518-1528.

Research output: Contribution to journalArticle

Tempero, M, Leichner, P, Dalrymple, G, Harrison, K, Augustine, S, Schlam, J, Anderson, J, Wisecarver, JL & Colcher, D 1997, 'High-dose therapy with iodine-131-labeled monoclonal antibody CC49 in patients with gastrointestinal cancers: A phase I trial', Journal of Clinical Oncology, vol. 15, no. 4, pp. 1518-1528. https://doi.org/10.1200/JCO.1997.15.4.1518
Tempero, M. ; Leichner, P. ; Dalrymple, G. ; Harrison, K. ; Augustine, S. ; Schlam, J. ; Anderson, J. ; Wisecarver, James Lowell ; Colcher, D. / High-dose therapy with iodine-131-labeled monoclonal antibody CC49 in patients with gastrointestinal cancers : A phase I trial. In: Journal of Clinical Oncology. 1997 ; Vol. 15, No. 4. pp. 1518-1528.
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abstract = "Purpose: A phase I trial that evaluated far extrahematopoietic toxicity was conducted with iodine- 131 (131I) labeled monoclonal antibody (MAb) CC49. Correlative studies included pharmacokinetic and biodistribution analyses, estimates of absorbed radiation dose, and measurement of human antimonoclonal antibodies (HAMA). Patients and Methods: After collection and cryopreservation of hematopoietic stem cells, 15 patients with gastrointestinal cancers were administered a tracer dose of 131I-MAb CC49. Within 5 to 6 days, 14 patients (two to three per activity level) underwent a single treatment with 131I-MAb CC49 (50, 100, 150, 200, 250, and 300 mCi/m2). Biodistribution was determined using planar and single photon emission computer tomographic (SPECT) imaging. Pharmacokinetic studies were performed by measuring radioactivity in serial blood samples. In some patients, biopsies of metastases and related normal tissues were obtained for radioactivity measurements. Radiation dosimetry/estimates were calculated using available biodistribution, pharmacokinetic, and tissue biopsy data. Toxicity was evaluated using the National Cancer Institute (NCI) Common Toxicity Criteria. Results: No dose-limiting extrahematopoietic toxicity was identified. Twelve patients experienced grade IV myelosuppression and met criteria for infusion of hematopoietic stem cells. Radioimmunolocalization was excellent. The T(1/2) for 131I-MAb CC49 after diagnostic and therapeutic administration was 39.7 ± 10.4 and 46.1 ± 10.6 hours, respectively. The percent injected dose per killigram of tumor ranged from 0.2 to 2.1. Absorbed radiation dose in metastatic tumor sites ranged from 630 to 3300 cGy. Conclusion: Although extrahematopoietic dose-limiting toxicity was neither observed or predicted, suboptimal absorbed dose estimates suggested that further escalation of 131I-MAb CC49 would not be useful. Future studies should focus on the use of radionuclides with high energy β emissions, such as yttrium90, and on strategies to optimize access of antibody to target antigens.",
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AU - Harrison, K.

AU - Augustine, S.

AU - Schlam, J.

AU - Anderson, J.

AU - Wisecarver, James Lowell

AU - Colcher, D.

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