Phase II study of cediranib (AZD 2171), an inhibitor of the vascular endothelial growth factor receptor, for second-line therapy of small cell lung cancer (National Cancer Institute #7097)

Suresh S. Ramalingam, Chandra P. Belani, Philip Mack, Everett E. Vokes, Jeffrey Longmate, Ramaswamy Govindan, Marianna Koczywas, S. Percy Ivy, David R Gandara

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Background: Inhibition of angiogenesis is a novel strategy for the treatment of cancer. We evaluated the safety and efficacy of cediranib, a potent small molecule inhibitor of the vascular endothelial growth factor receptor, in patients with refractory or recurrent small cell lung cancer (SCLC). Methods:Patients with SCLC with progression after prior platinum-based chemotherapy only; performance status (PS) of 0 to 2; and adequate bone marrow, renal, and hepatic function were included. The dose of cediranib was 45 mg PO once a day for the first 12 patients and was reduced to 30 mg PO once a day for the subsequent patients because of intolerance of the higher dose. Treatment was given on a daily continuous schedule. The primary end point was determination of the response rate. Results: Twenty-five patients were enrolled. Patient characteristics were as follows: 13 men; median age 61 years; PS 0 (12 pts), PS 1 (12 pts). A median of two cycles were administered. Salient grade 3/4 toxicities were fatigue, diarrhea, hypertension, proteinuria, and elevated liver enzymes. Tolerability was better with the 30 mg dose once a day. Nine patients had stable disease, but none had a confirmed partial response. The median progression-free survival and overall survival were 2 and 6 months, respectively. Response criteria to proceed to full accrual were not met. Increase in circulating endothelial cell count was noted at the time of progression in several patients. Conclusions: Cediranib failed to demonstrate objective responses in recurrent or refractory SCLC at the dose and schedule evaluated. The 45 mg dose was intolerable in a majority of SCLC patients.

Original languageEnglish (US)
Pages (from-to)1279-1284
Number of pages6
JournalJournal of Thoracic Oncology
Volume5
Issue number8
DOIs
StatePublished - Aug 2010

Fingerprint

Vascular Endothelial Growth Factor Receptor
National Cancer Institute (U.S.)
Small Cell Lung Carcinoma
Therapeutics
Appointments and Schedules
Endpoint Determination
cediranib
Liver
Platinum
Proteinuria
Disease-Free Survival
Fatigue
Diarrhea
Endothelial Cells
Cell Count
Bone Marrow
Hypertension
Kidney
Safety
Drug Therapy

Keywords

  • Angiogenesis
  • Biomarkers
  • Cediranib
  • Small cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Phase II study of cediranib (AZD 2171), an inhibitor of the vascular endothelial growth factor receptor, for second-line therapy of small cell lung cancer (National Cancer Institute #7097). / Ramalingam, Suresh S.; Belani, Chandra P.; Mack, Philip; Vokes, Everett E.; Longmate, Jeffrey; Govindan, Ramaswamy; Koczywas, Marianna; Ivy, S. Percy; Gandara, David R.

In: Journal of Thoracic Oncology, Vol. 5, No. 8, 08.2010, p. 1279-1284.

Research output: Contribution to journalArticle

Ramalingam, Suresh S. ; Belani, Chandra P. ; Mack, Philip ; Vokes, Everett E. ; Longmate, Jeffrey ; Govindan, Ramaswamy ; Koczywas, Marianna ; Ivy, S. Percy ; Gandara, David R. / Phase II study of cediranib (AZD 2171), an inhibitor of the vascular endothelial growth factor receptor, for second-line therapy of small cell lung cancer (National Cancer Institute #7097). In: Journal of Thoracic Oncology. 2010 ; Vol. 5, No. 8. pp. 1279-1284.
@article{2b35117e35584db3923a6a96ffd591c9,
title = "Phase II study of cediranib (AZD 2171), an inhibitor of the vascular endothelial growth factor receptor, for second-line therapy of small cell lung cancer (National Cancer Institute #7097)",
abstract = "Background: Inhibition of angiogenesis is a novel strategy for the treatment of cancer. We evaluated the safety and efficacy of cediranib, a potent small molecule inhibitor of the vascular endothelial growth factor receptor, in patients with refractory or recurrent small cell lung cancer (SCLC). Methods:Patients with SCLC with progression after prior platinum-based chemotherapy only; performance status (PS) of 0 to 2; and adequate bone marrow, renal, and hepatic function were included. The dose of cediranib was 45 mg PO once a day for the first 12 patients and was reduced to 30 mg PO once a day for the subsequent patients because of intolerance of the higher dose. Treatment was given on a daily continuous schedule. The primary end point was determination of the response rate. Results: Twenty-five patients were enrolled. Patient characteristics were as follows: 13 men; median age 61 years; PS 0 (12 pts), PS 1 (12 pts). A median of two cycles were administered. Salient grade 3/4 toxicities were fatigue, diarrhea, hypertension, proteinuria, and elevated liver enzymes. Tolerability was better with the 30 mg dose once a day. Nine patients had stable disease, but none had a confirmed partial response. The median progression-free survival and overall survival were 2 and 6 months, respectively. Response criteria to proceed to full accrual were not met. Increase in circulating endothelial cell count was noted at the time of progression in several patients. Conclusions: Cediranib failed to demonstrate objective responses in recurrent or refractory SCLC at the dose and schedule evaluated. The 45 mg dose was intolerable in a majority of SCLC patients.",
keywords = "Angiogenesis, Biomarkers, Cediranib, Small cell lung cancer",
author = "Ramalingam, {Suresh S.} and Belani, {Chandra P.} and Philip Mack and Vokes, {Everett E.} and Jeffrey Longmate and Ramaswamy Govindan and Marianna Koczywas and Ivy, {S. Percy} and Gandara, {David R}",
year = "2010",
month = "8",
doi = "10.1097/JTO.0b013e3181e2fcb0",
language = "English (US)",
volume = "5",
pages = "1279--1284",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",
number = "8",

}

TY - JOUR

T1 - Phase II study of cediranib (AZD 2171), an inhibitor of the vascular endothelial growth factor receptor, for second-line therapy of small cell lung cancer (National Cancer Institute #7097)

AU - Ramalingam, Suresh S.

AU - Belani, Chandra P.

AU - Mack, Philip

AU - Vokes, Everett E.

AU - Longmate, Jeffrey

AU - Govindan, Ramaswamy

AU - Koczywas, Marianna

AU - Ivy, S. Percy

AU - Gandara, David R

PY - 2010/8

Y1 - 2010/8

N2 - Background: Inhibition of angiogenesis is a novel strategy for the treatment of cancer. We evaluated the safety and efficacy of cediranib, a potent small molecule inhibitor of the vascular endothelial growth factor receptor, in patients with refractory or recurrent small cell lung cancer (SCLC). Methods:Patients with SCLC with progression after prior platinum-based chemotherapy only; performance status (PS) of 0 to 2; and adequate bone marrow, renal, and hepatic function were included. The dose of cediranib was 45 mg PO once a day for the first 12 patients and was reduced to 30 mg PO once a day for the subsequent patients because of intolerance of the higher dose. Treatment was given on a daily continuous schedule. The primary end point was determination of the response rate. Results: Twenty-five patients were enrolled. Patient characteristics were as follows: 13 men; median age 61 years; PS 0 (12 pts), PS 1 (12 pts). A median of two cycles were administered. Salient grade 3/4 toxicities were fatigue, diarrhea, hypertension, proteinuria, and elevated liver enzymes. Tolerability was better with the 30 mg dose once a day. Nine patients had stable disease, but none had a confirmed partial response. The median progression-free survival and overall survival were 2 and 6 months, respectively. Response criteria to proceed to full accrual were not met. Increase in circulating endothelial cell count was noted at the time of progression in several patients. Conclusions: Cediranib failed to demonstrate objective responses in recurrent or refractory SCLC at the dose and schedule evaluated. The 45 mg dose was intolerable in a majority of SCLC patients.

AB - Background: Inhibition of angiogenesis is a novel strategy for the treatment of cancer. We evaluated the safety and efficacy of cediranib, a potent small molecule inhibitor of the vascular endothelial growth factor receptor, in patients with refractory or recurrent small cell lung cancer (SCLC). Methods:Patients with SCLC with progression after prior platinum-based chemotherapy only; performance status (PS) of 0 to 2; and adequate bone marrow, renal, and hepatic function were included. The dose of cediranib was 45 mg PO once a day for the first 12 patients and was reduced to 30 mg PO once a day for the subsequent patients because of intolerance of the higher dose. Treatment was given on a daily continuous schedule. The primary end point was determination of the response rate. Results: Twenty-five patients were enrolled. Patient characteristics were as follows: 13 men; median age 61 years; PS 0 (12 pts), PS 1 (12 pts). A median of two cycles were administered. Salient grade 3/4 toxicities were fatigue, diarrhea, hypertension, proteinuria, and elevated liver enzymes. Tolerability was better with the 30 mg dose once a day. Nine patients had stable disease, but none had a confirmed partial response. The median progression-free survival and overall survival were 2 and 6 months, respectively. Response criteria to proceed to full accrual were not met. Increase in circulating endothelial cell count was noted at the time of progression in several patients. Conclusions: Cediranib failed to demonstrate objective responses in recurrent or refractory SCLC at the dose and schedule evaluated. The 45 mg dose was intolerable in a majority of SCLC patients.

KW - Angiogenesis

KW - Biomarkers

KW - Cediranib

KW - Small cell lung cancer

UR - http://www.scopus.com/inward/record.url?scp=77955094938&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955094938&partnerID=8YFLogxK

U2 - 10.1097/JTO.0b013e3181e2fcb0

DO - 10.1097/JTO.0b013e3181e2fcb0

M3 - Article

VL - 5

SP - 1279

EP - 1284

JO - Journal of Thoracic Oncology

JF - Journal of Thoracic Oncology

SN - 1556-0864

IS - 8

ER -