Phase II trial of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy Journal Article
| Authors: | Saltz, L. B.; Rosen, L. S.; Marshall, J. L.; Belt, R. J.; Hurwitz, H. I.; Eckhardt, S. G.; Bergsland, E. K.; Haller, D. G.; Lockhart, A. C.; Rocha Lima, C. M.; Huang, X.; Deprimo, S. E.; Chow-Maneval, E.; Chao, R. C.; Lenz, H. J. |
| Article Title: | Phase II trial of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy |
| Abstract: | Purpose: 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. Patients and 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 ≥ 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. Conclusion: 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. © 2007 by American Society of Clinical Oncology. |
| Keywords: | adult; treatment response; aged; bone neoplasms; middle aged; bone tumor; survival rate; major clinical study; overall survival; clinical trial; constipation; fatigue; neutropenia; salvage therapy; angiogenesis inhibitor; bevacizumab; fluorouracil; sunitinib; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; hypertension; liver neoplasms; antineoplastic agent; anorexia; colorectal cancer; vasculotropin receptor; metastasis; multiple cycle treatment; phase 2 clinical trial; cohort studies; peritoneal neoplasms; mucosa inflammation; nausea; stomatitis; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; lung neoplasms; dehydration; cohort analysis; pathology; protein tyrosine kinase; cetuximab; irinotecan; protein tyrosine kinase inhibitor; rash; colorectal neoplasms; lung tumor; drug mechanism; multicenter study; colorectal tumor; folinic acid; liver tumor; peripheral edema; skin discoloration; headache; drug metabolism; drug blood level; indoles; pyrroles; oxaliplatin; drug treatment failure; dyspepsia; hand foot syndrome; angiogenesis inhibitors; growth factor; indole derivative; fluoropyrimidine; peritoneum tumor; pyrrole derivative; mouth pain; perianal abscess |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 25 |
| Issue: | 30 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2007-10-20 |
| Start Page: | 4793 |
| End Page: | 4799 |
| Language: | English |
| DOI: | 10.1200/jco.2007.12.8637 |
| PUBMED: | 17947727 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 69" - "Export Date: 17 November 2011" - "CODEN: JCOND" - "Source: Scopus" |
