Evaluation of continuous infusion suramin in metastatic breast cancer: Impact on plasma levels of insulin-like growth factors (IGFs) and IGF- binding proteins

James B. Lawrence, Cheryl A Conover, Tufia C Haddad, James N. Ingle, Joel M Reid, Matthew M. Ames, Vera Jean Suman, Randolph Stuart Marks, Charles Erlichman, Lynn C. Hartmann

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Suramin represents a new class of antitumor drugs that targets growth factor networks. In this Phase II trial, suramin was administered by continuous infusion to 10 patients with advanced breast cancer. The target level of 280 μg/ml suramin was achieved in a median of 10 days; toxicities in this patient group were low. We monitored the insulin-like growth factor (IGF) network in these patients because of the previously defined growth- promoting role of the IGFs in breast cancer. Plasma levels of total IGF-I and total IGF-II showed variable responses to suramin with median decreases of 24 and 23%, respectively, for the 10 patients; for total IGF-I levels, this did not reach statistical significance. On the other hand, free IGF-I plasma levels were consistently and dramatically increased (over 250%) after suramin infusion. IGF-binding proteins (IGFBPs), modulators of IGF bioavailability, were also measured. Levels of IGFBP-3, the major carrier of IGFs in the circulation, were decreased 21% after suramin treatment when measured by immunoradiometric assay. However, the majority of the plasma IGFBP-3 remaining after suramin was not the intact high-affinity IGF-binding form but rather a 30-kDa fragment with markedly reduced affinity for IGF-I. IGFBP-3 protease activity was evident in the plasma of 3 of 10 patients after suramin. Measurements of plasma IGFBP-1, IGFBP-2, and IGFBP-4 revealed no significant changes in response to suramin. The dramatic increase in active free IGF-I seen after suramin raises concern and underscores the importance of measuring relevant biomarkers in clinical trials.

Original languageEnglish (US)
Pages (from-to)1713-1720
Number of pages8
JournalClinical Cancer Research
Volume3
Issue number10
StatePublished - Oct 1997

Fingerprint

Suramin
Insulin-Like Growth Factor Binding Proteins
Somatomedins
Breast Neoplasms
Insulin-Like Growth Factor I
Insulin-Like Growth Factor Binding Protein 3
Blood Proteins
Insulin-Like Growth Factor Binding Protein 4
Insulin-Like Growth Factor Binding Protein 2
Immunoradiometric Assay
Insulin-Like Growth Factor Binding Protein 1
Insulin-Like Growth Factor II
Antineoplastic Agents
Biological Availability
Intercellular Signaling Peptides and Proteins
Peptide Hydrolases
Biomarkers
Clinical Trials

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Evaluation of continuous infusion suramin in metastatic breast cancer : Impact on plasma levels of insulin-like growth factors (IGFs) and IGF- binding proteins. / Lawrence, James B.; Conover, Cheryl A; Haddad, Tufia C; Ingle, James N.; Reid, Joel M; Ames, Matthew M.; Suman, Vera Jean; Marks, Randolph Stuart; Erlichman, Charles; Hartmann, Lynn C.

In: Clinical Cancer Research, Vol. 3, No. 10, 10.1997, p. 1713-1720.

Research output: Contribution to journalArticle

@article{8e10fcf0d0e446e4bb121c761a77e327,
title = "Evaluation of continuous infusion suramin in metastatic breast cancer: Impact on plasma levels of insulin-like growth factors (IGFs) and IGF- binding proteins",
abstract = "Suramin represents a new class of antitumor drugs that targets growth factor networks. In this Phase II trial, suramin was administered by continuous infusion to 10 patients with advanced breast cancer. The target level of 280 μg/ml suramin was achieved in a median of 10 days; toxicities in this patient group were low. We monitored the insulin-like growth factor (IGF) network in these patients because of the previously defined growth- promoting role of the IGFs in breast cancer. Plasma levels of total IGF-I and total IGF-II showed variable responses to suramin with median decreases of 24 and 23{\%}, respectively, for the 10 patients; for total IGF-I levels, this did not reach statistical significance. On the other hand, free IGF-I plasma levels were consistently and dramatically increased (over 250{\%}) after suramin infusion. IGF-binding proteins (IGFBPs), modulators of IGF bioavailability, were also measured. Levels of IGFBP-3, the major carrier of IGFs in the circulation, were decreased 21{\%} after suramin treatment when measured by immunoradiometric assay. However, the majority of the plasma IGFBP-3 remaining after suramin was not the intact high-affinity IGF-binding form but rather a 30-kDa fragment with markedly reduced affinity for IGF-I. IGFBP-3 protease activity was evident in the plasma of 3 of 10 patients after suramin. Measurements of plasma IGFBP-1, IGFBP-2, and IGFBP-4 revealed no significant changes in response to suramin. The dramatic increase in active free IGF-I seen after suramin raises concern and underscores the importance of measuring relevant biomarkers in clinical trials.",
author = "Lawrence, {James B.} and Conover, {Cheryl A} and Haddad, {Tufia C} and Ingle, {James N.} and Reid, {Joel M} and Ames, {Matthew M.} and Suman, {Vera Jean} and Marks, {Randolph Stuart} and Charles Erlichman and Hartmann, {Lynn C.}",
year = "1997",
month = "10",
language = "English (US)",
volume = "3",
pages = "1713--1720",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "10",

}

TY - JOUR

T1 - Evaluation of continuous infusion suramin in metastatic breast cancer

T2 - Impact on plasma levels of insulin-like growth factors (IGFs) and IGF- binding proteins

AU - Lawrence, James B.

AU - Conover, Cheryl A

AU - Haddad, Tufia C

AU - Ingle, James N.

AU - Reid, Joel M

AU - Ames, Matthew M.

AU - Suman, Vera Jean

AU - Marks, Randolph Stuart

AU - Erlichman, Charles

AU - Hartmann, Lynn C.

PY - 1997/10

Y1 - 1997/10

N2 - Suramin represents a new class of antitumor drugs that targets growth factor networks. In this Phase II trial, suramin was administered by continuous infusion to 10 patients with advanced breast cancer. The target level of 280 μg/ml suramin was achieved in a median of 10 days; toxicities in this patient group were low. We monitored the insulin-like growth factor (IGF) network in these patients because of the previously defined growth- promoting role of the IGFs in breast cancer. Plasma levels of total IGF-I and total IGF-II showed variable responses to suramin with median decreases of 24 and 23%, respectively, for the 10 patients; for total IGF-I levels, this did not reach statistical significance. On the other hand, free IGF-I plasma levels were consistently and dramatically increased (over 250%) after suramin infusion. IGF-binding proteins (IGFBPs), modulators of IGF bioavailability, were also measured. Levels of IGFBP-3, the major carrier of IGFs in the circulation, were decreased 21% after suramin treatment when measured by immunoradiometric assay. However, the majority of the plasma IGFBP-3 remaining after suramin was not the intact high-affinity IGF-binding form but rather a 30-kDa fragment with markedly reduced affinity for IGF-I. IGFBP-3 protease activity was evident in the plasma of 3 of 10 patients after suramin. Measurements of plasma IGFBP-1, IGFBP-2, and IGFBP-4 revealed no significant changes in response to suramin. The dramatic increase in active free IGF-I seen after suramin raises concern and underscores the importance of measuring relevant biomarkers in clinical trials.

AB - Suramin represents a new class of antitumor drugs that targets growth factor networks. In this Phase II trial, suramin was administered by continuous infusion to 10 patients with advanced breast cancer. The target level of 280 μg/ml suramin was achieved in a median of 10 days; toxicities in this patient group were low. We monitored the insulin-like growth factor (IGF) network in these patients because of the previously defined growth- promoting role of the IGFs in breast cancer. Plasma levels of total IGF-I and total IGF-II showed variable responses to suramin with median decreases of 24 and 23%, respectively, for the 10 patients; for total IGF-I levels, this did not reach statistical significance. On the other hand, free IGF-I plasma levels were consistently and dramatically increased (over 250%) after suramin infusion. IGF-binding proteins (IGFBPs), modulators of IGF bioavailability, were also measured. Levels of IGFBP-3, the major carrier of IGFs in the circulation, were decreased 21% after suramin treatment when measured by immunoradiometric assay. However, the majority of the plasma IGFBP-3 remaining after suramin was not the intact high-affinity IGF-binding form but rather a 30-kDa fragment with markedly reduced affinity for IGF-I. IGFBP-3 protease activity was evident in the plasma of 3 of 10 patients after suramin. Measurements of plasma IGFBP-1, IGFBP-2, and IGFBP-4 revealed no significant changes in response to suramin. The dramatic increase in active free IGF-I seen after suramin raises concern and underscores the importance of measuring relevant biomarkers in clinical trials.

UR - http://www.scopus.com/inward/record.url?scp=0030879459&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030879459&partnerID=8YFLogxK

M3 - Article

C2 - 9815555

AN - SCOPUS:0030879459

VL - 3

SP - 1713

EP - 1720

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 10

ER -