Reference Detail

Ref Type Journal Article
PMID (20516450)
Authors Altorki N, Lane ME, Bauer T, Lee PC, Guarino MJ, Pass H, Felip E, Peylan-Ramu N, Gurpide A, Grannis FW, Mitchell JD, Tachdjian S, Swann RS, Huff A, Roychowdhury DF, Reeves A, Ottesen LH, Yankelevitz DF
Title Phase II proof-of-concept study of pazopanib monotherapy in treatment-naive patients with stage I/II resectable non-small-cell lung cancer.
Journal Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Vol 28
Issue 19
Date 2010 Jul 01
URL
Abstract Text Patients with early-stage, resectable, non-small-cell lung cancer (NSCLC) are at risk for recurrent disease, and 5-year survival rates do not exceed 75%. Angiogenesis inhibitors have shown clinical activity in patients with late-stage NSCLC, raising the possibility that targeting the vascular endothelial growth factor pathway in earlier-stage disease may be beneficial. This proof-of-concept study examined safety and efficacy of short-term, preoperative pazopanib monotherapy in patients with operable stage I/II NSCLC.Patients scheduled for resection received oral pazopanib 800 mg/d for 2 to 6 weeks preoperatively. Tumor response was measured by high-resolution computed tomography, permitting estimation of change in tumor volume and diameter. Gene-expression profiling was performed on 77 pre- and post-treatment lung samples from 34 patients.Of 35 patients enrolled, 33 (94%) had clinical stage I NSCLC and two (6%) had clinical stage II NSCLC. Median treatment duration was 16 days (range, 3 to 29 days). Thirty patients (86%) achieved tumor-volume reduction after pazopanib treatment. Two patients achieved tumor-volume reduction > or = 50%, and three patients had partial response according to Response Evaluation Criteria in Solid Tumors. Pazopanib was generally well tolerated. The most common adverse events included grade 2 hypertension, diarrhea, and fatigue. One patient developed pulmonary embolism 11 days after surgery. Several pazopanib target genes and other angiogenic factors were dysregulated post-treatment.Short-duration pazopanib was generally well tolerated and demonstrated single-agent activity in patients with early-stage NSCLC. Several target genes were dysregulated after pazopanib treatment, validating target-specific response and indicating a persistent pazopanib effect on lung cancer tissue. Further clinical evaluation of pazopanib in NSCLC is planned.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Therapy Description
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown non-small cell lung carcinoma not applicable Pazopanib Phase II Actionable In a Phase II trial, Votrient (pazopanib) treatment resulted in 86% (30/35) of patients with non-small cell lung cancer experiencing a decrease in tumor size, including one patient with a greater than 50% reduction, and resulted in a partial response based on RECIST criteria in three patients (PMID: 20516450). 20516450