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Cediranib In Patients With Malignant Mesothelioma: A Phase II Trial Of The University Of Chicago Phase II Consortium.

N. Campbell, R. Kunnavakkam, N. Leighl, M. Vincent, D. Gandara, M. Koczywas, B. Gitlitz, E. Agamah, S. Thomas, W. Stadler, E. Vokes, H. Kindler
Published 2012 · Medicine

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INTRODUCTION Malignant mesothelioma (MM) is an aggressive disease with limited therapeutic options. In preclinical models, vascular endothelial growth factor (VEGF) stimulates MM proliferation. In MM patients, higher plasma VEGF levels correlate inversely with survival. Cediranib is an orally administered tyrosine kinase inhibitor of VEGF receptors-1, -2, and -3. METHODS We conducted a multi-center phase II trial of cediranib in patients with unresectable, histologically-confirmed MM who had received ≤1 prior regimen of chemotherapy. The primary endpoint was objective response rate. Initial cediranib dosing was 45 mg daily during a 28-day cycle. Due to substantial toxicity, the starting dose was subsequently lowered to 30 mg daily. RESULTS Fifty-one patients enrolled at 9 centers; 50 were evaluable for response. Partial responses were observed in 10% of patients; stable disease was seen in 34%. Disease control (PR+SD) was higher at the 45 mg cediranib dose level (67% vs. 34%, p=0.04). Median progression-free survival was 1.8 months (95% CI 0.1, 14.2); median overall survival (OS) was 4.4 months (95% CI 0.9, 41.7). The 1-year survival rate was 15%. Grade 3/4 toxicities were more frequent in the 45 mg dose level group (87% vs. 43%, p=0.002). These included fatigue, hypertension, pulmonary embolism, angioedema, and reversible posterior leukoencephalopathy. Median OS was superior in patients who developed ≥grade 3 hypertension (8.5 vs. 4.1 months, p=0.024). CONCLUSION This trial did not meet its pre-specified response endpoint. A higher cediranib dose level was associated with improved disease control, but this dose was poorly tolerated.
This paper references
Hypertension and clinical benefit of bevacizumab in the treatment of advanced renal cell carcinoma.
P. Bono (2009)
Contrasting treatment‐specific survival using double‐robust estimators
K. Kim (2012)
Optimal two-stage designs for phase II clinical trials.
R. Simon (1989)
Arterial hypertension correlates with clinical outcome in colorectal cancer patients treated with first-line bevacizumab.
M. Scartozzi (2009)
A Phase II Study of Sorafenib in Malignant Mesothelioma: Results of Cancer and Leukemia Group B 30307
S. Dubey (2010)
Phase II Study of Cediranib in Patients with Malignant Pleural Mesothelioma: SWOG S0509
L. Garland (2011)
The predictive role of serum VEGF in an advanced malignant mesothelioma patient cohort treated with thalidomide alone or combined with cisplatin/gemcitabine.
S. Kao (2012)
Statistical Methods
G. W. Snedecor (1964)
Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis.
D. Hicklin (2005)
Thalidomide in patients with malignant pleural mesothelioma.
P. Baas (2005)
Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma.
N. Vogelzang (2003)
Update on malignant pleural mesothelioma.
N. Campbell (2011)
Nonparametric Estimation from Incomplete Observations
E. L. Kaplan (1958)
Multicenter, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin plus bevacizumab or placebo in patients with malignant mesothelioma.
H. Kindler (2012)
Vascular endothelial growth factor (VEGF) signaling in tumor progression.
R. Roskoski (2007)
Statistical methods
G. W. Snedecor (1980)
Clinical course of advanced non-small-cell lung cancer patients experiencing hypertension during treatment with bevacizumab in combination with carboplatin and paclitaxel on ECOG 4599.
S. Dahlberg (2010)
Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100.
B. Schneider (2008)
SU 5416 in malignant mesothelioma : a University of Chicago Phase II Consortium Study
H Kindler (2001)
Final results of a phase II trial of sunitinib as second - line therapy in malignant pleural mesothelioma
A Nowak (2010)
Role of protein kinase C β and vascular endothelial growth factor receptor in malignant pleural mesothelioma: Therapeutic implications and the usefulness of Caenorhabditis elegans model organism
S. Loganathan (2011)
AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer.
S. Wedge (2005)
Retreatment with pemetrexed-based chemotherapy in patients with malignant pleural mesothelioma.
G. Ceresoli (2011)
Modified RECIST criteria for assessment of response in malignant pleural mesothelioma.
M. Byrne (2004)
Hypertension induced by vascular endothelial growth factor signaling pathway inhibition: mechanisms and potential use as a biomarker.
E. Robinson (2010)
Final results of a phase II study of sunitinib as second-line therapy in malignant pleural mesothelioma (MPM).
A. Nowak (2010)
Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors.
J. Drevs (2007)
Vatalanib in malignant mesothelioma: a phase II trial by the Cancer and Leukemia Group B (CALGB 30107).
T. Jahan (2012)
[New response evaluation criteria in solid tumours-revised RECIST guideline (version 1.1)].
H. Watanabe (2009)

This paper is referenced by
New Results and Concepts in Systemic Treatment of Mesothelioma
Olga Olevsky (2014)
Pleural neoplastic pathology.
G. Karpathiou (2015)
Systematic review of response rates of sarcomatoid malignant pleural mesotheliomas in clinical trials.
A. Mansfield (2014)
ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma
A. Scherpereel (2020)
Molecular pathogenesis of malignant mesothelioma.
Y. Sekido (2013)
Systemic treatment of malignant pleural mesothelioma: new agents in clinical trials raise hope of relevant improvements
D. Christoph (2014)
Chemotherapy options versus "novel" therapies: how should we treat patients with malignant pleural mesothelioma.
M. Disselhorst (2020)
A review of bevacizumab in the treatment of malignant pleural mesothelioma.
S. Brosseau (2017)
Malignant Pleural Mesothelioma: State-of-the-Art on Current Therapies and Promises for the Future
Fabio Nicolini (2019)
Malignant pleural mesothelioma: new hope in the horizon with novel therapeutic strategies.
J. Remon (2015)
New therapeutic strategies for malignant pleural mesothelioma
M. Bonelli (2017)
Posterior reversible encephalopathy syndrome and takotsubo cardiomyopathy associated with lenvatinib therapy for thyroid cancer: a case report and review
Y. Chae (2018)
A phase II trial of dovitinib in previously-treated advanced pleural mesothelioma: The Ontario Clinical Oncology Group.
S. Laurie (2017)
Anti-Angiogenic Tyrosine Kinase Inhibitors and Reversible Posterior Leukoencephalopathy Syndrome: Could Hypomagnesaemia Be the Trigger?
R. Shah (2017)
Second line therapy in malignant pleural mesothelioma: A systematic review.
W. Buikhuisen (2015)
Searching for targets for the systemic therapy of mesothelioma.
R. Stahel (2015)
Risks of Proteinuria Associated with Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis
Ze-feng Zhang (2014)
ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma.
I. Opitz (2020)
The role of cediranib in ovarian cancer: current status and further investigation
J. Ethier (2016)
Targeting the Hippo Pathway Is a New Potential Therapeutic Modality for Malignant Mesothelioma
Y. Sekido (2018)
Advances in treatment of mesothelioma
C. Maggioni (2016)
Mesothelioma treatment: Are we on target? A review
B. Hiddinga (2015)
Novel systemic therapy against malignant pleural mesothelioma.
M. R. Mancuso (2017)
Targeting angiogenesis for patients with unresectable malignant pleural mesothelioma.
A. Tsao (2019)
An overview of angiogenesis inhibitors in Phase II studies for non-small-cell lung cancer
S. Pilotto (2015)
Molecular pathogenesis of malignant mesothelioma.
P. Rascoe (2012)
Mésothéliome pleural malin : la chimiothérapie est-elle la seule option thérapeutique ?
A. Scherpereel (2014)
Antiangiogeneic Strategies in Mesothelioma
A. Nowak (2020)
Latest developments in our understanding of the pathogenesis of mesothelioma and the design of targeted therapies
A. Bononi (2015)
Emerging therapies in malignant pleural mesothelioma.
M. Cinausero (2019)
Gremlin-1 is a key regulator of the invasive cell phenotype in mesothelioma
M. Yin (2017)
Spotlight on bevacizumab and its potential in the treatment of malignant pleural mesothelioma: the evidence to date
Pavel A. Levin (2017)
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