Phase II trial of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy

Leonard B. Saltz, Lee S. Rosen, John L. Marshall, Robert J. Belt, Herbert I. Hurwitz, S. Gail Eckhardt, Emily K. Bergsland, Daniel G. Haller, Albert Lockhart, Caio M. Rocha Lima, Xin Huang, Samuel E. DePrimo, Edna Chow-Maneval, Richard C. Chao, Heinz J. Lenz

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)4793-4799
Number of pages7
JournalJournal of Clinical Oncology
Volume25
Issue number30
DOIs
StatePublished - Oct 20 2007

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Colorectal Neoplasms
Therapeutics
Safety
Vascular Endothelial Growth Factor Receptor
Growth Factor Receptors
Receptor Protein-Tyrosine Kinases
Anorexia
sunitinib
Nausea
Vomiting
Fatigue
Bevacizumab
Diarrhea
Drug Therapy
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Saltz, L. B., Rosen, L. S., Marshall, J. L., Belt, R. J., Hurwitz, H. I., Eckhardt, S. G., ... Lenz, H. J. (2007). Phase II trial of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy. Journal of Clinical Oncology, 25(30), 4793-4799. https://doi.org/10.1200/JCO.2007.12.8637

Phase II trial of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy. / Saltz, Leonard B.; Rosen, Lee S.; Marshall, John L.; Belt, Robert J.; Hurwitz, Herbert I.; Eckhardt, S. Gail; Bergsland, Emily K.; Haller, Daniel G.; Lockhart, Albert; Rocha Lima, Caio M.; Huang, Xin; DePrimo, Samuel E.; Chow-Maneval, Edna; Chao, Richard C.; Lenz, Heinz J.

In: Journal of Clinical Oncology, Vol. 25, No. 30, 20.10.2007, p. 4793-4799.

Research output: Contribution to journalArticle

Saltz, LB, Rosen, LS, Marshall, JL, Belt, RJ, Hurwitz, HI, Eckhardt, SG, Bergsland, EK, Haller, DG, Lockhart, A, Rocha Lima, CM, Huang, X, DePrimo, SE, Chow-Maneval, E, Chao, RC & Lenz, HJ 2007, 'Phase II trial of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy', Journal of Clinical Oncology, vol. 25, no. 30, pp. 4793-4799. https://doi.org/10.1200/JCO.2007.12.8637
Saltz, Leonard B. ; Rosen, Lee S. ; Marshall, John L. ; Belt, Robert J. ; Hurwitz, Herbert I. ; Eckhardt, S. Gail ; Bergsland, Emily K. ; Haller, Daniel G. ; Lockhart, Albert ; Rocha Lima, Caio M. ; Huang, Xin ; DePrimo, Samuel E. ; Chow-Maneval, Edna ; Chao, Richard C. ; Lenz, Heinz J. / Phase II trial of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 30. pp. 4793-4799.
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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-na{\"i}ve 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.",
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AU - Eckhardt, S. Gail

AU - Bergsland, Emily K.

AU - Haller, Daniel G.

AU - Lockhart, Albert

AU - Rocha Lima, Caio M.

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N2 - 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.

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