Phase I/II trial of combined 131I anti-CEA monoclonal antibody and hyperthermia in patients with advanced colorectal adenocarcinoma

Bharat B Mittal*, A Michael Zimmer, Vythialingam Sathiaseelan, Al B Benson III, Raj R. Mittal, Swati Dutta, Steven T. Rosen, Stewart M Spies, Joanne M. Mettler, Mark W. Groch

*Corresponding author for this work

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

BACKGROUND. This pilot project was undertaken to evaluate the toxicity of and tumor response to combined 131I anti-carcinoembryonic antigen monoclonal antibody (131I anti-CEA RMoAb) and hyperemia in patients with metastatic colorectal adenocarcinoma. METHODS. Nine patients who had colorectal carcinoma with liver metastases were enrolled in this study. Intact 131I anti-CEA RMoAb was used (the specific antibody was IMMU-4, provided by Immunomedics, Inc., Morris Plains, NJ). During the diagnostic phase, dosimetry revealed that the tumor site received a higher radiation dose than the surrounding normal tissues in only six patients. These six, who were treated with radioimmunotherapy and hyperemia, were the basis of this study. The first three patients were treated with 30 mCi/m2 of 131I anti- CEA RMoAb, and the next three received 60 mCi/m2. Pharmacokinetics clearance data were reported for all nine patients. RESULTS. Thermometry data revealed an average T90 of 40.3 (±1.4°C) and T90 of 41.1 (±1.2°C). The average thermal dose equivalent at 42.5°C was 34.5 (±21.5) minutes. The average T(min), T(max), and T(mean) were 40 (±1.2°C), 42.4 (±0.7°C), and 41.1 (±1.1°C), respectively. The pharmacokinetics clearance data of antibody showed monoexponential plasma clearances in all patients except one, in whom a biexponential plasma clearance was observed. In general, similar plasma and whole-body clearances as well as similar urinary excretions were observed when diagnostic and therapeutic phases for each patient were compared. Two of the six patients showed a marked improvement in their symptoms; five patients showed a drop in carcinoembryonic antigen levels. A follow-up computed tomography scan one month after treatment showed no change in tumor volume in five patients; one patient showed a partial response. Three patients developed toxicity, two developed moderate thrombocytopenia (39,000 and 58,000), and the other patient developed hematoma resulting from the insertion of a catheter for thermometry. CONCLUSIONS. It is feasible to combine hyperemia and radiolabeled monoclonal antibodies, and the combination was well tolerated by these patients. The interaction between hyperemia and low dose rate radioimmunotherapy is complex. Further studies are necessary to explore the use of this combine modality in the management of malignancies.

Original languageEnglish (US)
Pages (from-to)1861-1870
Number of pages10
JournalCancer
Volume78
Issue number9
DOIs
StatePublished - Nov 1 1996

Fingerprint

Adenocarcinoma
Fever
Monoclonal Antibodies
Hyperemia
Thermometry
Radioimmunotherapy
Carcinoembryonic Antigen
Pharmacokinetics
Neoplasms
Antibodies
Tumor Burden
Thrombocytopenia
Hematoma
Colorectal Neoplasms
Catheters
Hot Temperature
Tomography
Radiation
Neoplasm Metastasis

Keywords

  • I-labeled anti-carcinoembryonic antigen monoclonal antibody
  • colorectal carcinoma
  • hyperthermia
  • liver metastases

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Mittal, Bharat B ; Zimmer, A Michael ; Sathiaseelan, Vythialingam ; Benson III, Al B ; Mittal, Raj R. ; Dutta, Swati ; Rosen, Steven T. ; Spies, Stewart M ; Mettler, Joanne M. ; Groch, Mark W. / Phase I/II trial of combined 131I anti-CEA monoclonal antibody and hyperthermia in patients with advanced colorectal adenocarcinoma. In: Cancer. 1996 ; Vol. 78, No. 9. pp. 1861-1870.
@article{4a3164aa968041118882f03ad14d7a29,
title = "Phase I/II trial of combined 131I anti-CEA monoclonal antibody and hyperthermia in patients with advanced colorectal adenocarcinoma",
abstract = "BACKGROUND. This pilot project was undertaken to evaluate the toxicity of and tumor response to combined 131I anti-carcinoembryonic antigen monoclonal antibody (131I anti-CEA RMoAb) and hyperemia in patients with metastatic colorectal adenocarcinoma. METHODS. Nine patients who had colorectal carcinoma with liver metastases were enrolled in this study. Intact 131I anti-CEA RMoAb was used (the specific antibody was IMMU-4, provided by Immunomedics, Inc., Morris Plains, NJ). During the diagnostic phase, dosimetry revealed that the tumor site received a higher radiation dose than the surrounding normal tissues in only six patients. These six, who were treated with radioimmunotherapy and hyperemia, were the basis of this study. The first three patients were treated with 30 mCi/m2 of 131I anti- CEA RMoAb, and the next three received 60 mCi/m2. Pharmacokinetics clearance data were reported for all nine patients. RESULTS. Thermometry data revealed an average T90 of 40.3 (±1.4°C) and T90 of 41.1 (±1.2°C). The average thermal dose equivalent at 42.5°C was 34.5 (±21.5) minutes. The average T(min), T(max), and T(mean) were 40 (±1.2°C), 42.4 (±0.7°C), and 41.1 (±1.1°C), respectively. The pharmacokinetics clearance data of antibody showed monoexponential plasma clearances in all patients except one, in whom a biexponential plasma clearance was observed. In general, similar plasma and whole-body clearances as well as similar urinary excretions were observed when diagnostic and therapeutic phases for each patient were compared. Two of the six patients showed a marked improvement in their symptoms; five patients showed a drop in carcinoembryonic antigen levels. A follow-up computed tomography scan one month after treatment showed no change in tumor volume in five patients; one patient showed a partial response. Three patients developed toxicity, two developed moderate thrombocytopenia (39,000 and 58,000), and the other patient developed hematoma resulting from the insertion of a catheter for thermometry. CONCLUSIONS. It is feasible to combine hyperemia and radiolabeled monoclonal antibodies, and the combination was well tolerated by these patients. The interaction between hyperemia and low dose rate radioimmunotherapy is complex. Further studies are necessary to explore the use of this combine modality in the management of malignancies.",
keywords = "I-labeled anti-carcinoembryonic antigen monoclonal antibody, colorectal carcinoma, hyperthermia, liver metastases",
author = "Mittal, {Bharat B} and Zimmer, {A Michael} and Vythialingam Sathiaseelan and {Benson III}, {Al B} and Mittal, {Raj R.} and Swati Dutta and Rosen, {Steven T.} and Spies, {Stewart M} and Mettler, {Joanne M.} and Groch, {Mark W.}",
year = "1996",
month = "11",
day = "1",
doi = "10.1002/(SICI)1097-0142(19961101)78:9<1861::AID-CNCR4>3.0.CO;2-I",
language = "English (US)",
volume = "78",
pages = "1861--1870",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "9",

}

Phase I/II trial of combined 131I anti-CEA monoclonal antibody and hyperthermia in patients with advanced colorectal adenocarcinoma. / Mittal, Bharat B; Zimmer, A Michael; Sathiaseelan, Vythialingam; Benson III, Al B; Mittal, Raj R.; Dutta, Swati; Rosen, Steven T.; Spies, Stewart M; Mettler, Joanne M.; Groch, Mark W.

In: Cancer, Vol. 78, No. 9, 01.11.1996, p. 1861-1870.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase I/II trial of combined 131I anti-CEA monoclonal antibody and hyperthermia in patients with advanced colorectal adenocarcinoma

AU - Mittal, Bharat B

AU - Zimmer, A Michael

AU - Sathiaseelan, Vythialingam

AU - Benson III, Al B

AU - Mittal, Raj R.

AU - Dutta, Swati

AU - Rosen, Steven T.

AU - Spies, Stewart M

AU - Mettler, Joanne M.

AU - Groch, Mark W.

PY - 1996/11/1

Y1 - 1996/11/1

N2 - BACKGROUND. This pilot project was undertaken to evaluate the toxicity of and tumor response to combined 131I anti-carcinoembryonic antigen monoclonal antibody (131I anti-CEA RMoAb) and hyperemia in patients with metastatic colorectal adenocarcinoma. METHODS. Nine patients who had colorectal carcinoma with liver metastases were enrolled in this study. Intact 131I anti-CEA RMoAb was used (the specific antibody was IMMU-4, provided by Immunomedics, Inc., Morris Plains, NJ). During the diagnostic phase, dosimetry revealed that the tumor site received a higher radiation dose than the surrounding normal tissues in only six patients. These six, who were treated with radioimmunotherapy and hyperemia, were the basis of this study. The first three patients were treated with 30 mCi/m2 of 131I anti- CEA RMoAb, and the next three received 60 mCi/m2. Pharmacokinetics clearance data were reported for all nine patients. RESULTS. Thermometry data revealed an average T90 of 40.3 (±1.4°C) and T90 of 41.1 (±1.2°C). The average thermal dose equivalent at 42.5°C was 34.5 (±21.5) minutes. The average T(min), T(max), and T(mean) were 40 (±1.2°C), 42.4 (±0.7°C), and 41.1 (±1.1°C), respectively. The pharmacokinetics clearance data of antibody showed monoexponential plasma clearances in all patients except one, in whom a biexponential plasma clearance was observed. In general, similar plasma and whole-body clearances as well as similar urinary excretions were observed when diagnostic and therapeutic phases for each patient were compared. Two of the six patients showed a marked improvement in their symptoms; five patients showed a drop in carcinoembryonic antigen levels. A follow-up computed tomography scan one month after treatment showed no change in tumor volume in five patients; one patient showed a partial response. Three patients developed toxicity, two developed moderate thrombocytopenia (39,000 and 58,000), and the other patient developed hematoma resulting from the insertion of a catheter for thermometry. CONCLUSIONS. It is feasible to combine hyperemia and radiolabeled monoclonal antibodies, and the combination was well tolerated by these patients. The interaction between hyperemia and low dose rate radioimmunotherapy is complex. Further studies are necessary to explore the use of this combine modality in the management of malignancies.

AB - BACKGROUND. This pilot project was undertaken to evaluate the toxicity of and tumor response to combined 131I anti-carcinoembryonic antigen monoclonal antibody (131I anti-CEA RMoAb) and hyperemia in patients with metastatic colorectal adenocarcinoma. METHODS. Nine patients who had colorectal carcinoma with liver metastases were enrolled in this study. Intact 131I anti-CEA RMoAb was used (the specific antibody was IMMU-4, provided by Immunomedics, Inc., Morris Plains, NJ). During the diagnostic phase, dosimetry revealed that the tumor site received a higher radiation dose than the surrounding normal tissues in only six patients. These six, who were treated with radioimmunotherapy and hyperemia, were the basis of this study. The first three patients were treated with 30 mCi/m2 of 131I anti- CEA RMoAb, and the next three received 60 mCi/m2. Pharmacokinetics clearance data were reported for all nine patients. RESULTS. Thermometry data revealed an average T90 of 40.3 (±1.4°C) and T90 of 41.1 (±1.2°C). The average thermal dose equivalent at 42.5°C was 34.5 (±21.5) minutes. The average T(min), T(max), and T(mean) were 40 (±1.2°C), 42.4 (±0.7°C), and 41.1 (±1.1°C), respectively. The pharmacokinetics clearance data of antibody showed monoexponential plasma clearances in all patients except one, in whom a biexponential plasma clearance was observed. In general, similar plasma and whole-body clearances as well as similar urinary excretions were observed when diagnostic and therapeutic phases for each patient were compared. Two of the six patients showed a marked improvement in their symptoms; five patients showed a drop in carcinoembryonic antigen levels. A follow-up computed tomography scan one month after treatment showed no change in tumor volume in five patients; one patient showed a partial response. Three patients developed toxicity, two developed moderate thrombocytopenia (39,000 and 58,000), and the other patient developed hematoma resulting from the insertion of a catheter for thermometry. CONCLUSIONS. It is feasible to combine hyperemia and radiolabeled monoclonal antibodies, and the combination was well tolerated by these patients. The interaction between hyperemia and low dose rate radioimmunotherapy is complex. Further studies are necessary to explore the use of this combine modality in the management of malignancies.

KW - I-labeled anti-carcinoembryonic antigen monoclonal antibody

KW - colorectal carcinoma

KW - hyperthermia

KW - liver metastases

UR - http://www.scopus.com/inward/record.url?scp=10244263486&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10244263486&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-0142(19961101)78:9<1861::AID-CNCR4>3.0.CO;2-I

DO - 10.1002/(SICI)1097-0142(19961101)78:9<1861::AID-CNCR4>3.0.CO;2-I

M3 - Article

C2 - 8909304

AN - SCOPUS:10244263486

VL - 78

SP - 1861

EP - 1870

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 9

ER -