Phase II study of cisplatin plus etoposide and bevacizumab for previously untreated, extensive-stage small-cell lung cancer

Eastern cooperative oncology group study E3501

Leora Horn, Suzanne E. Dahlberg, Alan B. Sandler, Afshin Dowlati, Dennis F. Moore, John R. Murren, Joan H. Schiller

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

Purpose: To investigate the efficacy and safety of bevacizumab plus cisplatin and etoposide in patients with extensive-stage disease, small-cell lung cancer (ED-SCLC). Patients and Methods: In this phase II trial, 63 patients were treated with bevacizumab 15 mg/kg plus cisplatin 60 mg/m2 and etoposide 120 mg/m2, which was followed by bevacizumab alone until death or disease progression occurred. The primary end point was the proportion of patients alive at 6 months without disease progression (ie, progression-free survival [PFS]). Secondary end points included overall survival (OS), objective response rate, and toxicity. Correlative studies were performed to explore the relationship between baseline and changes in plasma vascular endothelial growth factor (VEGF), soluble cell adhesion molecules (ie, vascular cell adhesion molecule [VCAM], intercellular cell adhesion molecule [ICAM], and E-selectin) and basic fibroblast growth factor and outcome. Results: The 6-month PFS was 30.2%, the median PFS was 4.7 months, and OS was 10.9 months. The response rate was 63.5%. The most common adverse event was neutropenia (57.8%). Only one patient had grade 3 pulmonary hemorrhage. Patients who had high baseline VCAM had a higher risk of progression or death compared with those who had low baseline VCAM levels. No relationships between outcome and any other biomarkers were seen. Conclusion: The addition of bevacizumab to cisplatin and etoposide in patients with ED-SCLC results in improved PFS and OS relative to historical controls who received this chemotherapy regimen without bevacizumab. This regimen appears to be well tolerated and has minimal increase in toxicities compared with chemotherapy alone. Baseline VCAM levels predicted survival, but no other relationships among treatment, biomarkers, and outcome were identified.

Original languageEnglish (US)
Pages (from-to)6006-6011
Number of pages6
JournalJournal of Clinical Oncology
Volume27
Issue number35
DOIs
StatePublished - Dec 10 2009

Fingerprint

Small Cell Lung Carcinoma
Etoposide
Cisplatin
Vascular Cell Adhesion Molecule-1
Disease-Free Survival
Cell Adhesion Molecules
Survival
Disease Progression
Biomarkers
Drug Therapy
E-Selectin
Fibroblast Growth Factor 2
Bevacizumab
Neutropenia
Vascular Endothelial Growth Factor A
Hemorrhage
Safety
Lung

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Phase II study of cisplatin plus etoposide and bevacizumab for previously untreated, extensive-stage small-cell lung cancer : Eastern cooperative oncology group study E3501. / Horn, Leora; Dahlberg, Suzanne E.; Sandler, Alan B.; Dowlati, Afshin; Moore, Dennis F.; Murren, John R.; Schiller, Joan H.

In: Journal of Clinical Oncology, Vol. 27, No. 35, 10.12.2009, p. 6006-6011.

Research output: Contribution to journalArticle

Horn, Leora ; Dahlberg, Suzanne E. ; Sandler, Alan B. ; Dowlati, Afshin ; Moore, Dennis F. ; Murren, John R. ; Schiller, Joan H. / Phase II study of cisplatin plus etoposide and bevacizumab for previously untreated, extensive-stage small-cell lung cancer : Eastern cooperative oncology group study E3501. In: Journal of Clinical Oncology. 2009 ; Vol. 27, No. 35. pp. 6006-6011.
@article{71dbe80d79454f9fbda6db71618d524a,
title = "Phase II study of cisplatin plus etoposide and bevacizumab for previously untreated, extensive-stage small-cell lung cancer: Eastern cooperative oncology group study E3501",
abstract = "Purpose: To investigate the efficacy and safety of bevacizumab plus cisplatin and etoposide in patients with extensive-stage disease, small-cell lung cancer (ED-SCLC). Patients and Methods: In this phase II trial, 63 patients were treated with bevacizumab 15 mg/kg plus cisplatin 60 mg/m2 and etoposide 120 mg/m2, which was followed by bevacizumab alone until death or disease progression occurred. The primary end point was the proportion of patients alive at 6 months without disease progression (ie, progression-free survival [PFS]). Secondary end points included overall survival (OS), objective response rate, and toxicity. Correlative studies were performed to explore the relationship between baseline and changes in plasma vascular endothelial growth factor (VEGF), soluble cell adhesion molecules (ie, vascular cell adhesion molecule [VCAM], intercellular cell adhesion molecule [ICAM], and E-selectin) and basic fibroblast growth factor and outcome. Results: The 6-month PFS was 30.2{\%}, the median PFS was 4.7 months, and OS was 10.9 months. The response rate was 63.5{\%}. The most common adverse event was neutropenia (57.8{\%}). Only one patient had grade 3 pulmonary hemorrhage. Patients who had high baseline VCAM had a higher risk of progression or death compared with those who had low baseline VCAM levels. No relationships between outcome and any other biomarkers were seen. Conclusion: The addition of bevacizumab to cisplatin and etoposide in patients with ED-SCLC results in improved PFS and OS relative to historical controls who received this chemotherapy regimen without bevacizumab. This regimen appears to be well tolerated and has minimal increase in toxicities compared with chemotherapy alone. Baseline VCAM levels predicted survival, but no other relationships among treatment, biomarkers, and outcome were identified.",
author = "Leora Horn and Dahlberg, {Suzanne E.} and Sandler, {Alan B.} and Afshin Dowlati and Moore, {Dennis F.} and Murren, {John R.} and Schiller, {Joan H.}",
year = "2009",
month = "12",
day = "10",
doi = "10.1200/JCO.2009.23.7545",
language = "English (US)",
volume = "27",
pages = "6006--6011",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "35",

}

TY - JOUR

T1 - Phase II study of cisplatin plus etoposide and bevacizumab for previously untreated, extensive-stage small-cell lung cancer

T2 - Eastern cooperative oncology group study E3501

AU - Horn, Leora

AU - Dahlberg, Suzanne E.

AU - Sandler, Alan B.

AU - Dowlati, Afshin

AU - Moore, Dennis F.

AU - Murren, John R.

AU - Schiller, Joan H.

PY - 2009/12/10

Y1 - 2009/12/10

N2 - Purpose: To investigate the efficacy and safety of bevacizumab plus cisplatin and etoposide in patients with extensive-stage disease, small-cell lung cancer (ED-SCLC). Patients and Methods: In this phase II trial, 63 patients were treated with bevacizumab 15 mg/kg plus cisplatin 60 mg/m2 and etoposide 120 mg/m2, which was followed by bevacizumab alone until death or disease progression occurred. The primary end point was the proportion of patients alive at 6 months without disease progression (ie, progression-free survival [PFS]). Secondary end points included overall survival (OS), objective response rate, and toxicity. Correlative studies were performed to explore the relationship between baseline and changes in plasma vascular endothelial growth factor (VEGF), soluble cell adhesion molecules (ie, vascular cell adhesion molecule [VCAM], intercellular cell adhesion molecule [ICAM], and E-selectin) and basic fibroblast growth factor and outcome. Results: The 6-month PFS was 30.2%, the median PFS was 4.7 months, and OS was 10.9 months. The response rate was 63.5%. The most common adverse event was neutropenia (57.8%). Only one patient had grade 3 pulmonary hemorrhage. Patients who had high baseline VCAM had a higher risk of progression or death compared with those who had low baseline VCAM levels. No relationships between outcome and any other biomarkers were seen. Conclusion: The addition of bevacizumab to cisplatin and etoposide in patients with ED-SCLC results in improved PFS and OS relative to historical controls who received this chemotherapy regimen without bevacizumab. This regimen appears to be well tolerated and has minimal increase in toxicities compared with chemotherapy alone. Baseline VCAM levels predicted survival, but no other relationships among treatment, biomarkers, and outcome were identified.

AB - Purpose: To investigate the efficacy and safety of bevacizumab plus cisplatin and etoposide in patients with extensive-stage disease, small-cell lung cancer (ED-SCLC). Patients and Methods: In this phase II trial, 63 patients were treated with bevacizumab 15 mg/kg plus cisplatin 60 mg/m2 and etoposide 120 mg/m2, which was followed by bevacizumab alone until death or disease progression occurred. The primary end point was the proportion of patients alive at 6 months without disease progression (ie, progression-free survival [PFS]). Secondary end points included overall survival (OS), objective response rate, and toxicity. Correlative studies were performed to explore the relationship between baseline and changes in plasma vascular endothelial growth factor (VEGF), soluble cell adhesion molecules (ie, vascular cell adhesion molecule [VCAM], intercellular cell adhesion molecule [ICAM], and E-selectin) and basic fibroblast growth factor and outcome. Results: The 6-month PFS was 30.2%, the median PFS was 4.7 months, and OS was 10.9 months. The response rate was 63.5%. The most common adverse event was neutropenia (57.8%). Only one patient had grade 3 pulmonary hemorrhage. Patients who had high baseline VCAM had a higher risk of progression or death compared with those who had low baseline VCAM levels. No relationships between outcome and any other biomarkers were seen. Conclusion: The addition of bevacizumab to cisplatin and etoposide in patients with ED-SCLC results in improved PFS and OS relative to historical controls who received this chemotherapy regimen without bevacizumab. This regimen appears to be well tolerated and has minimal increase in toxicities compared with chemotherapy alone. Baseline VCAM levels predicted survival, but no other relationships among treatment, biomarkers, and outcome were identified.

UR - http://www.scopus.com/inward/record.url?scp=73349099070&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73349099070&partnerID=8YFLogxK

U2 - 10.1200/JCO.2009.23.7545

DO - 10.1200/JCO.2009.23.7545

M3 - Article

VL - 27

SP - 6006

EP - 6011

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 35

ER -