Phase I/II radioimmunotherapy trial with iodine-131-labeled monoclonal antibody G250 in metastatic renal cell carcinoma

Chaitanya R. Divgi, Neil H. Bander, Andrew M. Scott, Joseph A. O'Donoghue, George Sgouros, Sydney Welt, Ronald D. Finn, Francesca Morrissey, Peter Capitelli, Jeanne M. Williams, Devie Deland, Aparna Nakhre, Egbert Oosterwijk, Seza Gulec, Martin C. Graham, Steven M. Larson, Lloyd J. Old

Research output: Contribution to journalArticle

Abstract

This Phase I/II radioimmunotherapy study was carried out to determine the maximum tolerated dose (MTD) and therapeutic potential of 131I-G250. Thirty-three patients with measurable metastatic renal cell carcinoma were treated. Groups of at least three patients received escalating amounts of 131I (30, 45, 60, 75, and 90 mCi/m2) labeled to 10 mg of mouse monoclonal antibody G250, administered as a single i.v. infusion. Fifteen patients were studied at the MTD of activity. No patient had received prior significant radiotherapy; one had received prior G250. Whole-body scintigrams and single- photon emission computed tomography images were obtained in all patients. There was targeting of radioactivity to all known tumor sites that were ≥2 cm. Reversible liver function test abnormalities were observed in the majority of patients (27 of 33 patients). There was no correlation between the amount of 131I administered or hepatic absorbed radiation dose (median, 0.073 Gy/mCi) and the extent or nature of hepatic toxicity. Two of the first six patients at 90 mCi/m2 had grade ≥3 thrombocytopenia; the MTD was determined to be 90 mCi/m2 131I. Hematological toxicity was correlated with whole-body absorbed radiation dose. All patients developed human antimouse antibodies within 4 weeks posttherapy; retreatment was, therefore, not possible. Seventeen of 33 evaluable patients had stable disease. There were no major responses. On the basis of external imaging, 131I-labeled mouse monoclonal antibody G250 showed excellent localization to all tumors that were ≥2 cm. Seventeen of 33 patients had stable disease, with tumor shrinkage observed in two patients. Antibody immunogenicity restricted therapy to a single infusion. Studies with a nonimmunogenic G250 antibody are warranted.

Original languageEnglish (US)
Pages (from-to)2729-2739
Number of pages11
JournalClinical Cancer Research
Volume4
Issue number11
StatePublished - Nov 1998
Externally publishedYes

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Radioimmunotherapy
Renal Cell Carcinoma
Iodine
Maximum Tolerated Dose
G250 monoclonal antibody
Antibodies
Neoplasms
Retreatment
Whole-Body Irradiation
Liver
Liver Function Tests
Single-Photon Emission-Computed Tomography
Radioactivity

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Divgi, C. R., Bander, N. H., Scott, A. M., O'Donoghue, J. A., Sgouros, G., Welt, S., ... Old, L. J. (1998). Phase I/II radioimmunotherapy trial with iodine-131-labeled monoclonal antibody G250 in metastatic renal cell carcinoma. Clinical Cancer Research, 4(11), 2729-2739.

Phase I/II radioimmunotherapy trial with iodine-131-labeled monoclonal antibody G250 in metastatic renal cell carcinoma. / Divgi, Chaitanya R.; Bander, Neil H.; Scott, Andrew M.; O'Donoghue, Joseph A.; Sgouros, George; Welt, Sydney; Finn, Ronald D.; Morrissey, Francesca; Capitelli, Peter; Williams, Jeanne M.; Deland, Devie; Nakhre, Aparna; Oosterwijk, Egbert; Gulec, Seza; Graham, Martin C.; Larson, Steven M.; Old, Lloyd J.

In: Clinical Cancer Research, Vol. 4, No. 11, 11.1998, p. 2729-2739.

Research output: Contribution to journalArticle

Divgi, CR, Bander, NH, Scott, AM, O'Donoghue, JA, Sgouros, G, Welt, S, Finn, RD, Morrissey, F, Capitelli, P, Williams, JM, Deland, D, Nakhre, A, Oosterwijk, E, Gulec, S, Graham, MC, Larson, SM & Old, LJ 1998, 'Phase I/II radioimmunotherapy trial with iodine-131-labeled monoclonal antibody G250 in metastatic renal cell carcinoma', Clinical Cancer Research, vol. 4, no. 11, pp. 2729-2739.
Divgi, Chaitanya R. ; Bander, Neil H. ; Scott, Andrew M. ; O'Donoghue, Joseph A. ; Sgouros, George ; Welt, Sydney ; Finn, Ronald D. ; Morrissey, Francesca ; Capitelli, Peter ; Williams, Jeanne M. ; Deland, Devie ; Nakhre, Aparna ; Oosterwijk, Egbert ; Gulec, Seza ; Graham, Martin C. ; Larson, Steven M. ; Old, Lloyd J. / Phase I/II radioimmunotherapy trial with iodine-131-labeled monoclonal antibody G250 in metastatic renal cell carcinoma. In: Clinical Cancer Research. 1998 ; Vol. 4, No. 11. pp. 2729-2739.
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abstract = "This Phase I/II radioimmunotherapy study was carried out to determine the maximum tolerated dose (MTD) and therapeutic potential of 131I-G250. Thirty-three patients with measurable metastatic renal cell carcinoma were treated. Groups of at least three patients received escalating amounts of 131I (30, 45, 60, 75, and 90 mCi/m2) labeled to 10 mg of mouse monoclonal antibody G250, administered as a single i.v. infusion. Fifteen patients were studied at the MTD of activity. No patient had received prior significant radiotherapy; one had received prior G250. Whole-body scintigrams and single- photon emission computed tomography images were obtained in all patients. There was targeting of radioactivity to all known tumor sites that were ≥2 cm. Reversible liver function test abnormalities were observed in the majority of patients (27 of 33 patients). There was no correlation between the amount of 131I administered or hepatic absorbed radiation dose (median, 0.073 Gy/mCi) and the extent or nature of hepatic toxicity. Two of the first six patients at 90 mCi/m2 had grade ≥3 thrombocytopenia; the MTD was determined to be 90 mCi/m2 131I. Hematological toxicity was correlated with whole-body absorbed radiation dose. All patients developed human antimouse antibodies within 4 weeks posttherapy; retreatment was, therefore, not possible. Seventeen of 33 evaluable patients had stable disease. There were no major responses. On the basis of external imaging, 131I-labeled mouse monoclonal antibody G250 showed excellent localization to all tumors that were ≥2 cm. Seventeen of 33 patients had stable disease, with tumor shrinkage observed in two patients. Antibody immunogenicity restricted therapy to a single infusion. Studies with a nonimmunogenic G250 antibody are warranted.",
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AU - Sgouros, George

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AU - Finn, Ronald D.

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AU - Williams, Jeanne M.

AU - Deland, Devie

AU - Nakhre, Aparna

AU - Oosterwijk, Egbert

AU - Gulec, Seza

AU - Graham, Martin C.

AU - Larson, Steven M.

AU - Old, Lloyd J.

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N2 - This Phase I/II radioimmunotherapy study was carried out to determine the maximum tolerated dose (MTD) and therapeutic potential of 131I-G250. Thirty-three patients with measurable metastatic renal cell carcinoma were treated. Groups of at least three patients received escalating amounts of 131I (30, 45, 60, 75, and 90 mCi/m2) labeled to 10 mg of mouse monoclonal antibody G250, administered as a single i.v. infusion. Fifteen patients were studied at the MTD of activity. No patient had received prior significant radiotherapy; one had received prior G250. Whole-body scintigrams and single- photon emission computed tomography images were obtained in all patients. There was targeting of radioactivity to all known tumor sites that were ≥2 cm. Reversible liver function test abnormalities were observed in the majority of patients (27 of 33 patients). There was no correlation between the amount of 131I administered or hepatic absorbed radiation dose (median, 0.073 Gy/mCi) and the extent or nature of hepatic toxicity. Two of the first six patients at 90 mCi/m2 had grade ≥3 thrombocytopenia; the MTD was determined to be 90 mCi/m2 131I. Hematological toxicity was correlated with whole-body absorbed radiation dose. All patients developed human antimouse antibodies within 4 weeks posttherapy; retreatment was, therefore, not possible. Seventeen of 33 evaluable patients had stable disease. There were no major responses. On the basis of external imaging, 131I-labeled mouse monoclonal antibody G250 showed excellent localization to all tumors that were ≥2 cm. Seventeen of 33 patients had stable disease, with tumor shrinkage observed in two patients. Antibody immunogenicity restricted therapy to a single infusion. Studies with a nonimmunogenic G250 antibody are warranted.

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