Choosing an optimal radioimmunotherapy dose for clinical response

Sally J. DeNardo, Lawrence E. Williams, Bryan R. Leigh, Richard L. Wahl

Research output: Contribution to journalArticle

Abstract

Clinical trials have documented the single-agent efficacy of radioimmunotherapy (RIT) in lymphoma, and several combination therapy studies are now in progress. RIT agents are currently becoming generally available for clinical use in lymphoma therapy. Solid tumors, which are notoriously less responsive to any single agent, have demonstrated clinically useful responses, albeit temporary, and multimodality studies have been instituted. However, a sincere debate continues regarding the basic parameters to be used to define appropriate therapeutic dosing when using this modality in clinical cancer care. It is a good time to reevaluate relevant dose response information from preclinical and clinical RIT. Preclinical studies have demonstrated abundant evidence of dose response in tumor and normal tissue in homogenous model systems; however, substantive variation occurs between the dose responses of tumors with low and variable (or shed) antigen expression, as well as between histologically different tumor models. Clinical studies of various heavily pretreated patient populations given several very different RIT pharmaceuticals have led to disparate conclusions regarding patient dosing methods and dosimetric predictions of toxicity and efficacy. Single-study data on previously untreated lymphoma patients with similar histology has demonstrated a correlation of imaging dosimetry with toxicity and tumor response. High-dose therapy with bone marrow support has also demonstrated a high tumor response rate and nonmarrow normal organ toxicities that correlate with the calculated dose to those organs from imaging. In iodine-131 (131I)-anti-CD20 studies, 131I was demonstrated to have variable excretion, and estimated total-body radiation dose from tracer study proved a predictive surrogate for marrow toxicity. Yttrium-90 (90Y)-anti-CD20, which has little 90Y excretion from the body, demonstrated the injected dose per body weight to be more predictive of marrow toxicity than indium-111 (111In) tracer dosimetry methods in heavily pretreated patients, and showed maximal safety with standard mCi/kg therapy dosing. Variations in clinical RIT choices, dosing methods, and dosimetry methods emphasize the need to review the relevant information to date. Future clinical trial designs, the sophistication of dosimetry, treatment planning, and clinical treatment decisions should all be focused on achieving the best benefit-risk relationship for each patient.

Original languageEnglish (US)
Pages (from-to)1275-1286
Number of pages12
JournalCancer
Volume94
Issue number4 SUPPL.
StatePublished - Feb 15 2002

Fingerprint

Radioimmunotherapy
Neoplasms
Lymphoma
Bone Marrow
Therapeutics
Clinical Trials
Yttrium
Indium
Iodine
Histology
Body Weight
Radiation
Safety
Antigens
Pharmaceutical Preparations

Keywords

  • Dose-related response
  • Dosimetry
  • Lymphoma
  • Radioimmunotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

DeNardo, S. J., Williams, L. E., Leigh, B. R., & Wahl, R. L. (2002). Choosing an optimal radioimmunotherapy dose for clinical response. Cancer, 94(4 SUPPL.), 1275-1286.

Choosing an optimal radioimmunotherapy dose for clinical response. / DeNardo, Sally J.; Williams, Lawrence E.; Leigh, Bryan R.; Wahl, Richard L.

In: Cancer, Vol. 94, No. 4 SUPPL., 15.02.2002, p. 1275-1286.

Research output: Contribution to journalArticle

DeNardo, SJ, Williams, LE, Leigh, BR & Wahl, RL 2002, 'Choosing an optimal radioimmunotherapy dose for clinical response', Cancer, vol. 94, no. 4 SUPPL., pp. 1275-1286.
DeNardo SJ, Williams LE, Leigh BR, Wahl RL. Choosing an optimal radioimmunotherapy dose for clinical response. Cancer. 2002 Feb 15;94(4 SUPPL.):1275-1286.
DeNardo, Sally J. ; Williams, Lawrence E. ; Leigh, Bryan R. ; Wahl, Richard L. / Choosing an optimal radioimmunotherapy dose for clinical response. In: Cancer. 2002 ; Vol. 94, No. 4 SUPPL. pp. 1275-1286.
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