Phase I trial of iodine 131-labeled COL-1 in patients with gastrointestinal malignancies: Influence of serum carcinoembryonic antigen and tumor bulk on pharmacokinetics

B. Yu, J. Carrasquillo, D. Milenic, Y. Chung, P. Perentesis, I. Feuerestein, D. Eggensperger, C. F. Qi, C. Paik, J. Reynolds, J. Grem, G. Curt, K. Siler, J. Schlom, C. Allegra

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Purpose: COL-1 is a high-affinity murine monoclonal antibody (MAb) specific for carcinoembryonic antigen (CEA). A phase I trial was conducted in which a uniform quantity of antibody labeled with escalating doses of iodine 131 (131I) was administered to patients with advanced gastrointestinal (GI) malignancies to evaluate tolerance and pharmacokinetics. Patients and Methods: Eighteen patients with advanced, assessable GI malignancies (16 colon, one pancreas, and one gastric) previously treated with conventional chemotherapy (but no pelvic radiation) received 20 mg of COL-1 labeled with 131I, with doses from 10 mCi/m2 to 75 mCi/m2. In this cohort, the baseline serum CEA level ranged from 6 to 2,739 ng/mL (mean ± SD, 500 ± 639). Results: Nuclear imaging detected at least one tumor site in all 18 patients; 82% of all tumor involved organs were positive and 58% of all lesions ≥ 1.0 cm were detected. Immune complexes were detected in 89% of patients 5 minutes after completion of infusion, and levels correlated with CEA levels (r = .71). Elevated CEA (> 500 ng/mL) and tumor bulk (total tumor area > 150 cm2) correlated directly with clearance of serum radioactivity and inversely with serum half-life and cumulative serum radioactivity parameters. Nonhematologic toxicity was mild and non-dose-limiting. Hematologic toxicity, particularly thrombocytopenia, was both dose-related and dose-limiting. The maximal-tolerated dose is 65 mCi/m2. The correlation between dose (millicuries per square meter) and thrombocytopenia was made stranger, by accounting for either variation in pharmacokinetics, or variation in serum CEA and tumor bulk. Conclusion: 131I-COL-1 is well tolerated, except for hematologic toxicity. These data suggest that patients with highly elevated circulating CEA levels and/or increased tumor bulk may clear 131I-labeled COL-1 more rapidly from the circulation and experience less myelosuppression.

Original languageEnglish (US)
Pages (from-to)1798-1809
Number of pages12
JournalJournal of Clinical Oncology
Volume14
Issue number6
DOIs
StatePublished - Jun 1996

Fingerprint

Carcinoembryonic Antigen
Iodine
Pharmacokinetics
Serum
Neoplasms
Thrombocytopenia
Radioactivity
Maximum Tolerated Dose
Antigen-Antibody Complex
Half-Life
Pancreas
Stomach
Colon
Monoclonal Antibodies
Radiation
Drug Therapy
Antibodies

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Phase I trial of iodine 131-labeled COL-1 in patients with gastrointestinal malignancies : Influence of serum carcinoembryonic antigen and tumor bulk on pharmacokinetics. / Yu, B.; Carrasquillo, J.; Milenic, D.; Chung, Y.; Perentesis, P.; Feuerestein, I.; Eggensperger, D.; Qi, C. F.; Paik, C.; Reynolds, J.; Grem, J.; Curt, G.; Siler, K.; Schlom, J.; Allegra, C.

In: Journal of Clinical Oncology, Vol. 14, No. 6, 06.1996, p. 1798-1809.

Research output: Contribution to journalArticle

Yu, B, Carrasquillo, J, Milenic, D, Chung, Y, Perentesis, P, Feuerestein, I, Eggensperger, D, Qi, CF, Paik, C, Reynolds, J, Grem, J, Curt, G, Siler, K, Schlom, J & Allegra, C 1996, 'Phase I trial of iodine 131-labeled COL-1 in patients with gastrointestinal malignancies: Influence of serum carcinoembryonic antigen and tumor bulk on pharmacokinetics', Journal of Clinical Oncology, vol. 14, no. 6, pp. 1798-1809. https://doi.org/10.1200/JCO.1996.14.6.1798
Yu, B. ; Carrasquillo, J. ; Milenic, D. ; Chung, Y. ; Perentesis, P. ; Feuerestein, I. ; Eggensperger, D. ; Qi, C. F. ; Paik, C. ; Reynolds, J. ; Grem, J. ; Curt, G. ; Siler, K. ; Schlom, J. ; Allegra, C. / Phase I trial of iodine 131-labeled COL-1 in patients with gastrointestinal malignancies : Influence of serum carcinoembryonic antigen and tumor bulk on pharmacokinetics. In: Journal of Clinical Oncology. 1996 ; Vol. 14, No. 6. pp. 1798-1809.
@article{a9cc55e3257d468b977df7c275288150,
title = "Phase I trial of iodine 131-labeled COL-1 in patients with gastrointestinal malignancies: Influence of serum carcinoembryonic antigen and tumor bulk on pharmacokinetics",
abstract = "Purpose: COL-1 is a high-affinity murine monoclonal antibody (MAb) specific for carcinoembryonic antigen (CEA). A phase I trial was conducted in which a uniform quantity of antibody labeled with escalating doses of iodine 131 (131I) was administered to patients with advanced gastrointestinal (GI) malignancies to evaluate tolerance and pharmacokinetics. Patients and Methods: Eighteen patients with advanced, assessable GI malignancies (16 colon, one pancreas, and one gastric) previously treated with conventional chemotherapy (but no pelvic radiation) received 20 mg of COL-1 labeled with 131I, with doses from 10 mCi/m2 to 75 mCi/m2. In this cohort, the baseline serum CEA level ranged from 6 to 2,739 ng/mL (mean ± SD, 500 ± 639). Results: Nuclear imaging detected at least one tumor site in all 18 patients; 82{\%} of all tumor involved organs were positive and 58{\%} of all lesions ≥ 1.0 cm were detected. Immune complexes were detected in 89{\%} of patients 5 minutes after completion of infusion, and levels correlated with CEA levels (r = .71). Elevated CEA (> 500 ng/mL) and tumor bulk (total tumor area > 150 cm2) correlated directly with clearance of serum radioactivity and inversely with serum half-life and cumulative serum radioactivity parameters. Nonhematologic toxicity was mild and non-dose-limiting. Hematologic toxicity, particularly thrombocytopenia, was both dose-related and dose-limiting. The maximal-tolerated dose is 65 mCi/m2. The correlation between dose (millicuries per square meter) and thrombocytopenia was made stranger, by accounting for either variation in pharmacokinetics, or variation in serum CEA and tumor bulk. Conclusion: 131I-COL-1 is well tolerated, except for hematologic toxicity. These data suggest that patients with highly elevated circulating CEA levels and/or increased tumor bulk may clear 131I-labeled COL-1 more rapidly from the circulation and experience less myelosuppression.",
author = "B. Yu and J. Carrasquillo and D. Milenic and Y. Chung and P. Perentesis and I. Feuerestein and D. Eggensperger and Qi, {C. F.} and C. Paik and J. Reynolds and J. Grem and G. Curt and K. Siler and J. Schlom and C. Allegra",
year = "1996",
month = "6",
doi = "10.1200/JCO.1996.14.6.1798",
language = "English (US)",
volume = "14",
pages = "1798--1809",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "6",

}

TY - JOUR

T1 - Phase I trial of iodine 131-labeled COL-1 in patients with gastrointestinal malignancies

T2 - Influence of serum carcinoembryonic antigen and tumor bulk on pharmacokinetics

AU - Yu, B.

AU - Carrasquillo, J.

AU - Milenic, D.

AU - Chung, Y.

AU - Perentesis, P.

AU - Feuerestein, I.

AU - Eggensperger, D.

AU - Qi, C. F.

AU - Paik, C.

AU - Reynolds, J.

AU - Grem, J.

AU - Curt, G.

AU - Siler, K.

AU - Schlom, J.

AU - Allegra, C.

PY - 1996/6

Y1 - 1996/6

N2 - Purpose: COL-1 is a high-affinity murine monoclonal antibody (MAb) specific for carcinoembryonic antigen (CEA). A phase I trial was conducted in which a uniform quantity of antibody labeled with escalating doses of iodine 131 (131I) was administered to patients with advanced gastrointestinal (GI) malignancies to evaluate tolerance and pharmacokinetics. Patients and Methods: Eighteen patients with advanced, assessable GI malignancies (16 colon, one pancreas, and one gastric) previously treated with conventional chemotherapy (but no pelvic radiation) received 20 mg of COL-1 labeled with 131I, with doses from 10 mCi/m2 to 75 mCi/m2. In this cohort, the baseline serum CEA level ranged from 6 to 2,739 ng/mL (mean ± SD, 500 ± 639). Results: Nuclear imaging detected at least one tumor site in all 18 patients; 82% of all tumor involved organs were positive and 58% of all lesions ≥ 1.0 cm were detected. Immune complexes were detected in 89% of patients 5 minutes after completion of infusion, and levels correlated with CEA levels (r = .71). Elevated CEA (> 500 ng/mL) and tumor bulk (total tumor area > 150 cm2) correlated directly with clearance of serum radioactivity and inversely with serum half-life and cumulative serum radioactivity parameters. Nonhematologic toxicity was mild and non-dose-limiting. Hematologic toxicity, particularly thrombocytopenia, was both dose-related and dose-limiting. The maximal-tolerated dose is 65 mCi/m2. The correlation between dose (millicuries per square meter) and thrombocytopenia was made stranger, by accounting for either variation in pharmacokinetics, or variation in serum CEA and tumor bulk. Conclusion: 131I-COL-1 is well tolerated, except for hematologic toxicity. These data suggest that patients with highly elevated circulating CEA levels and/or increased tumor bulk may clear 131I-labeled COL-1 more rapidly from the circulation and experience less myelosuppression.

AB - Purpose: COL-1 is a high-affinity murine monoclonal antibody (MAb) specific for carcinoembryonic antigen (CEA). A phase I trial was conducted in which a uniform quantity of antibody labeled with escalating doses of iodine 131 (131I) was administered to patients with advanced gastrointestinal (GI) malignancies to evaluate tolerance and pharmacokinetics. Patients and Methods: Eighteen patients with advanced, assessable GI malignancies (16 colon, one pancreas, and one gastric) previously treated with conventional chemotherapy (but no pelvic radiation) received 20 mg of COL-1 labeled with 131I, with doses from 10 mCi/m2 to 75 mCi/m2. In this cohort, the baseline serum CEA level ranged from 6 to 2,739 ng/mL (mean ± SD, 500 ± 639). Results: Nuclear imaging detected at least one tumor site in all 18 patients; 82% of all tumor involved organs were positive and 58% of all lesions ≥ 1.0 cm were detected. Immune complexes were detected in 89% of patients 5 minutes after completion of infusion, and levels correlated with CEA levels (r = .71). Elevated CEA (> 500 ng/mL) and tumor bulk (total tumor area > 150 cm2) correlated directly with clearance of serum radioactivity and inversely with serum half-life and cumulative serum radioactivity parameters. Nonhematologic toxicity was mild and non-dose-limiting. Hematologic toxicity, particularly thrombocytopenia, was both dose-related and dose-limiting. The maximal-tolerated dose is 65 mCi/m2. The correlation between dose (millicuries per square meter) and thrombocytopenia was made stranger, by accounting for either variation in pharmacokinetics, or variation in serum CEA and tumor bulk. Conclusion: 131I-COL-1 is well tolerated, except for hematologic toxicity. These data suggest that patients with highly elevated circulating CEA levels and/or increased tumor bulk may clear 131I-labeled COL-1 more rapidly from the circulation and experience less myelosuppression.

UR - http://www.scopus.com/inward/record.url?scp=8944222567&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=8944222567&partnerID=8YFLogxK

U2 - 10.1200/JCO.1996.14.6.1798

DO - 10.1200/JCO.1996.14.6.1798

M3 - Article

C2 - 8656248

AN - SCOPUS:8944222567

VL - 14

SP - 1798

EP - 1809

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 6

ER -