Dataset Information

Cediranib in patients with malignant mesothelioma: a phase II trial of the University of Chicago Phase II Consortium.

ABSTRACT: 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.

SUBMITTER: Campbell NP

PROVIDER: S-EPMC4319647 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cediranib in patients with malignant mesothelioma: a phase II trial of the University of Chicago Phase II Consortium.

Campbell Nicholas P NP Kunnavakkam Rangesh R Leighl Natasha N Vincent Mark D MD Gandara David R DR Koczywas Marianna M Gitlitz Barbara J BJ Agamah Edem E Thomas Sachdev P SP Stadler Walter M WM Vokes Everett E EE Kindler Hedy L HL

Lung cancer (Amsterdam, Netherlands) 20120723 1

<h4>Introduction</h4>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.<h4>Methods</h4>We conducted a multi-center phase II trial of cediranib in patients with unresectable, histologically-confirmed ...[more]

PMID: 22831987

Similar Datasets

Project description:PurposeAntiangiogenic agents combined with chemotherapy have efficacy in the treatment of unresectable malignant pleural mesothelioma (MPM). Cediranib (AstraZeneca, Cheshire, United Kingdom), a vascular endothelial growth factor receptor and platelet-derived growth factor receptor inhibitor, demonstrated therapeutic potential in a prior phase I trial. We evaluated a phase II trial for efficacy.Patients and methodsSWOG S0905 (ClinicalTrials.gov identifier: NCT01064648) randomly assigned cediranib or placebo with platinum-pemetrexed for six cycles followed by maintenance cediranib or placebo in unresectable chemotherapy-naïve patients with MPM of any histologic subtype. Primary end point was Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 progression-free survival (PFS). Secondary end points included overall survival, PFS by modified RECIST v1.1, response (modified RECIST and RECIST v1.1), disease control, and safety/toxicity. The trial was designed to detect a difference in RECIST v1.1 PFS at the one-sided 0.1 level using a stratified log-rank test.ResultsNinety-two eligible patients were enrolled (75% epithelioid and 25% biphasic or sarcomatoid). The cediranib arm had more grade 3 and 4 diarrhea, dehydration, hypertension, and weight loss. Cediranib improved PFS by RECIST v1.1 (hazard ratio, 0.71; 80% CI, 0.54 to 0.95; P = .062; 7.2 months v 5.6 months) and increased modified RECIST v1.1 response (50% v 20%; P = .006). By modified RECIST v1.1, cediranib numerically increased PFS (hazard ratio, 0.77; 80% CI, 0.59 to 1.02; P = .12; median, 6.9 months v 5.6 months). No significant difference in overall survival was observed.ConclusionThe addition of cediranib to platinum-pemetrexed improved PFS by RECIST v1.1 and response rate by modified RECIST in patients with unresectable MPM. Whereas adding antiangiogenics to chemotherapy has been a successful strategy for some patients, the cediranib toxicity profile and small incremental survival benefit precludes additional development in MPM.

Dataset Information

Cediranib in patients with malignant mesothelioma: a phase II trial of the University of Chicago Phase II Consortium.

Publications

Cediranib in patients with malignant mesothelioma: a phase II trial of the University of Chicago Phase II Consortium.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets