TY - JOUR
T1 - Phase II proof-of-concept study of pazopanib monotherapy in treatment-naive patients with stage I/II resectable non - small-cell lung cancer
AU - Altorki, Nasser
AU - Lane, Maureen E.
AU - Bauer, Thomas
AU - Lee, Paul C.
AU - Guarino, Michael J.
AU - Pass, Harvey
AU - Felip, Enriqueta
AU - Peylan-Ramu, Nili
AU - Gurpide, Alfonso
AU - Grannis, Frederic W.
AU - Mitchell, John D.
AU - Tachdjian, Sabrina
AU - Swann, R. Suzanne
AU - Huff, Anne
AU - Roychowdhury, Debasish F.
AU - Reeves, Anthony
AU - Ottesen, Lone H.
AU - Yankelevitz, David F.
PY - 2010/7/1
Y1 - 2010/7/1
N2 - Purpose: 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 and Methods: 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. Results: 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 ≥ 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. Conclusion: 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.
AB - Purpose: 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 and Methods: 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. Results: 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 ≥ 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. Conclusion: 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.
UR - http://www.scopus.com/inward/record.url?scp=77955503066&partnerID=8YFLogxK
U2 - 10.1200/JCO.2009.23.9749
DO - 10.1200/JCO.2009.23.9749
M3 - Article
C2 - 20516450
AN - SCOPUS:77955503066
SN - 0732-183X
VL - 28
SP - 3131
EP - 3137
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 19
ER -