Hematologic Toxicity in Radioimmunotherapy: Dose-Response Relationships for I-131 Labeled Antibody Therapy

O'Donoghue, Joseph A.; Baidoo, Nanaefua; Deland, Devie; Welt, Sydney; Divgi, Chaitanya R.; Sgouros, George

doi:10.1089/108497802760363222

Cited by 55Radiopharmaceutical Chemistry and ApplicationsEffects of Radiation ExposureMedical Imaging Techniques and Applications

Hematologic Toxicity in Radioimmunotherapy: Dose-Response Relationships for I-131 Labeled Antibody Therapy

O'Donoghue, Joseph A., Baidoo, Nanaefua, Deland, Devie, Welt, Sydney, Divgi, Chaitanya R., Sgouros, George·2002·Cancer Biotherapy and Radiopharmaceuticals

DOI 10.1089/108497802760363222

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Abstract

UNLABELLED: Bone marrow toxicity is generally dose-limiting for radioimmunotherapy (RIT) with beta-emitting radionuclides. Treatment may be prescribed on the basis of administered activity or absorbed dose. An optimal definition of maximum tolerated dose will enable the clinical benefits of RIT to be maximized. METHODS: We examined data from six clinical studies of RIT with various 131-I labeled antibodies and antibody fragments that treated a total of 114 patients. We also examined a sub-set of 36 patients with minimal prior chemotherapy who were treated with 131I-labeled intact murine IgG at a single institution. For both these groups the ability of absorbed dose-based methods to predict bone marrow tolerance was compared with that of activity-based methods. RESULTS: Marrow toxicity was more accurately predicted by absorbed dose than by activity in the general case where a variety of different antibodies and antibody fragments were used. For the more homogeneous smaller group, well defined "dose-response" relationships were observed for both absorbed dose and administered activity. However, absorbed dose-based definitions of maximally tolerated dose yielded a better stratification of patients than activity-based definitions (including per meter squared) such that fewer patients had major toxicity when treated below "tolerance", and fewer patients had minor toxicity when treated above "tolerance". CONCLUSIONS: Absorbed dose-based definitions of maximum tolerated dose and escalation variables are optimal for 131I-labeled antibody therapy. The ability of pre-therapy dosimetry studies to predict the behavior of therapeutic administrations must be validated for prospective clinical applications.

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Authors: O'Donoghue, J. A., Baidoo, N., Deland, D., Welt, S., Divgi, C. R., & Sgouros, G.
Affiliations: Memorial Sloan-Kettering Cancer Center and Ludwig Institute for Cancer Research, New York, NY 10021.
Memorial Sloan Kettering Cancer Center (US)
ORCID: Divgi, Chaitanya R.
Sgouros, George
Venue: Cancer Biotherapy and Radiopharmaceuticals
Publisher: SAGE Publications
Published: 2002-08
Volume: 17
Issue: 4
Pages: 435-443
ISSN: 1084-9785 (ISSN-L)
1557-8852
DOI: 10.1089/108497802760363222
OpenAlex: W2056667995
Cited by: 55
References: 16
Citations by year: 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 3 · 2017: 3 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 3
FWCI: 2.87
Type: journal article
Language: en
Open access: closed
Licence: www.liebertpub.com/nv/resources-tools/text-and-data-mining-policy/121/ (tdm)
Locations: Cancer Biotherapy and Radiopharmaceuticals (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Energy
National Cancer Institute (P01 CA33049, R01CA62444, P01CA033049, R01CA062444)
Topics: Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
Keywords: radioimmunotherapy, iodine-131, antibody therapy, hematologic toxicity, myelosuppression, absorbed dose, administered activity, dose-response relationship, maximum tolerated dose, antibody fragments
MeSH terms: Blood Platelets, Bone Marrow, Dose-Response Relationship, Radiation, Humans, Iodine Radioisotopes, Probability, Radiation Dosage, Radioimmunotherapy, Maximum Tolerated Dose

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Hematologic Toxicity in Radioimmunotherapy: Dose-Response Relationships for I-131 Labeled Antibody Therapy

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