Phase II proof-of-concept study of pazopanib monotherapy in treatment-naive patients with stage I/II resectable non-small-cell lung cancer.
OBJECTIVE
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.


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 > 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.


CONCLUSIONS
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.
Altorki
Nasser
N
Weill Medical College, Cornell University, 525 East 68th St, New York, NY 10021, USA. nkaltork@med.cornell.edu
Lane
Maureen E
ME
Bauer
Thomas
T
Lee
Paul C
PC
Guarino
Michael J
MJ
Pass
Harvey
H
Felip
Enriqueta
E
Peylan-Ramu
Nili
N
Gurpide
Alfonso
A
Grannis
Frederic W
FW
Mitchell
John D
JD
Tachdjian
Sabrina
S
Swann
R Suzanne
RS
Huff
Anne
A
Roychowdhury
Debasish F
DF
Reeves
Anthony
A
Ottesen
Lone H
LH
Yankelevitz
David F
DF
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007191:Indazoles; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib