Phase II trial of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy.
OBJECTIVE
Sunitinib is an oral, multitargeted receptor tyrosine kinase inhibitor of the vascular endothelial growth factor receptor and multiple other growth factor receptors. We assessed the safety and efficacy of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy.


METHODS
Eighty-four patients were enrolled onto this two-stage phase II trial and were stratified by whether they had received prior bevacizumab (n = 43) or not (n = 41). Treatment comprised sunitinib 50 mg orally daily for 4 weeks, followed by 2 weeks off treatment, in repeated 6-week cycles.


RESULTS
By Response Evaluation Criteria in Solid Tumors criteria, one patient, who was in the prior bevacizumab cohort, achieved a partial response, and 13 patients (two in the prior bevacizumab cohort and 11 in the no prior bevacizumab cohort) achieved stable disease lasting > or = 22 weeks. Median time to progression in the prior bevacizumab and bevacizumab-naïve cohorts was 2.2 months (95% CI, 1.9 to 2.3 months) and 2.5 months (95% CI, 2.3 to 3.1 months), respectively, whereas median overall survival time was 7.1 months (95% CI, 4.9 to 10.6 months) and 10.2 months (95% CI, 8.2 to 15.3 months), respectively. The most common adverse events were fatigue, diarrhea, nausea, vomiting, and anorexia. Twenty-six patients (32%) required dose reduction to 37.5 mg/d, and one patient required dose reduction to 25 mg/d.


CONCLUSIONS
Sunitinib did not demonstrate a meaningful single-agent objective response rate in colorectal cancer refractory to standard chemotherapy. However, the mechanisms of action and acceptable safety profile of sunitinib warrant further study in combination with standard regimens for metastatic colorectal cancer.
Saltz
Leonard B
LB
Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. saltzl@mskcc.org
Rosen
Lee S
LS
Marshall
John L
JL
Belt
Robert J
RJ
Hurwitz
Herbert I
HI
Eckhardt
S Gail
SG
Bergsland
Emily K
EK
Haller
Daniel G
DG
Lockhart
A Craig
AC
Rocha Lima
Caio M
CM
Huang
Xin
X
DePrimo
Samuel E
SE
Chow-Maneval
Edna
E
Chao
Richard C
RC
Lenz
Heinz J
HJ
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000556:secondary; D011379:Prognosis; D011758:Pyrroles / Q000627:therapeutic use*; D016879:Salvage Therapy; D000077210:Sunitinib; D015996:Survival Rate
D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib