Phase II trial of vatalanib in patients with advanced or metastatic pancreatic adenocarcinoma after first-line gemcitabine therapy (PCRT O4-001)

T. Dragovich, Daniel Laheru, F. Dayyani, V. Bolejack, L. Smith, J. Seng, H. Burris, P. Rosen, M. Hidalgo, P. Ritch, A. F. Baker, N. Raghunand, J. Crowley, D. D. Von Hoff

Research output: Contribution to journalArticle

Abstract

Purpose: Vatalanib (PTK 787/ZK22584) is an oral poly-tyrosine kinase inhibitor with strong affinity for platelet-derived growth factor and vascular endothelial growth factor (VEGF) receptors. We conducted an open-label, phase II multicenter therapeutic trial investigating the efficacy and tolerability of vatalanib in patients with metastatic or advanced pancreatic cancer who failed first-line gemcitabine-based therapy. Methods: Vatalanib treatment consisted of a twice daily oral dosing using a "ramp-up schedule," beginning with 250 mg bid during week 1,500 mg bid during week 2, and 750 mg bid on week three and thereafter. The primary objective of this study was to evaluate the 6-month survival rate. Results: Sixty-seven patients were enrolled. The median age was 64, and 66 % (N = 43) had only one prior regimen. Common grade 3/4 adverse events included hypertension (20 %; N = 13), fatigue (17 %; N = 11), abdominal pain (17 %; N = 11), and elevated alkaline phosphatase (15 %; N = 10). Among the 65 evaluable patients, the 6-month survival rate was 29 % (95 % CI 18-41 %) and the median progression-free survival was 2 months. Fifteen patients survived 6 months or more. Two patients had objective partial responses, and 28 % of patients had stable disease. Changes in biomarkers including soluble VEGF and vascular endothelial growth factor receptor did not correlate with response to drug. Conclusion: Vatalanib was well tolerated as a second-line therapy and resulted in favorable 6-month survival rate in patients with metastatic pancreatic cancer, compared with historic controls.

Original languageEnglish (US)
Pages (from-to)379-387
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Volume74
Issue number2
DOIs
StatePublished - 2014

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gemcitabine
Adenocarcinoma
Vascular Endothelial Growth Factor Receptor
Survival Rate
Pancreatic Neoplasms
Therapeutics
Platelet-Derived Growth Factor
Biomarkers
Protein-Tyrosine Kinases
Vascular Endothelial Growth Factor A
Alkaline Phosphatase
Architectural Accessibility
Labels
vatalanib
Fatigue of materials
Abdominal Pain
Multicenter Studies
Disease-Free Survival
Fatigue
Appointments and Schedules

Keywords

  • Pancreatic adenocarcinoma
  • Second-line treatment
  • Tyrosine kinase inhibitor
  • Vatalinib

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this

Phase II trial of vatalanib in patients with advanced or metastatic pancreatic adenocarcinoma after first-line gemcitabine therapy (PCRT O4-001). / Dragovich, T.; Laheru, Daniel; Dayyani, F.; Bolejack, V.; Smith, L.; Seng, J.; Burris, H.; Rosen, P.; Hidalgo, M.; Ritch, P.; Baker, A. F.; Raghunand, N.; Crowley, J.; Von Hoff, D. D.

In: Cancer Chemotherapy and Pharmacology, Vol. 74, No. 2, 2014, p. 379-387.

Research output: Contribution to journalArticle

Dragovich, T, Laheru, D, Dayyani, F, Bolejack, V, Smith, L, Seng, J, Burris, H, Rosen, P, Hidalgo, M, Ritch, P, Baker, AF, Raghunand, N, Crowley, J & Von Hoff, DD 2014, 'Phase II trial of vatalanib in patients with advanced or metastatic pancreatic adenocarcinoma after first-line gemcitabine therapy (PCRT O4-001)', Cancer Chemotherapy and Pharmacology, vol. 74, no. 2, pp. 379-387. https://doi.org/10.1007/s00280-014-2499-4
Dragovich, T. ; Laheru, Daniel ; Dayyani, F. ; Bolejack, V. ; Smith, L. ; Seng, J. ; Burris, H. ; Rosen, P. ; Hidalgo, M. ; Ritch, P. ; Baker, A. F. ; Raghunand, N. ; Crowley, J. ; Von Hoff, D. D. / Phase II trial of vatalanib in patients with advanced or metastatic pancreatic adenocarcinoma after first-line gemcitabine therapy (PCRT O4-001). In: Cancer Chemotherapy and Pharmacology. 2014 ; Vol. 74, No. 2. pp. 379-387.
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abstract = "Purpose: Vatalanib (PTK 787/ZK22584) is an oral poly-tyrosine kinase inhibitor with strong affinity for platelet-derived growth factor and vascular endothelial growth factor (VEGF) receptors. We conducted an open-label, phase II multicenter therapeutic trial investigating the efficacy and tolerability of vatalanib in patients with metastatic or advanced pancreatic cancer who failed first-line gemcitabine-based therapy. Methods: Vatalanib treatment consisted of a twice daily oral dosing using a {"}ramp-up schedule,{"} beginning with 250 mg bid during week 1,500 mg bid during week 2, and 750 mg bid on week three and thereafter. The primary objective of this study was to evaluate the 6-month survival rate. Results: Sixty-seven patients were enrolled. The median age was 64, and 66 {\%} (N = 43) had only one prior regimen. Common grade 3/4 adverse events included hypertension (20 {\%}; N = 13), fatigue (17 {\%}; N = 11), abdominal pain (17 {\%}; N = 11), and elevated alkaline phosphatase (15 {\%}; N = 10). Among the 65 evaluable patients, the 6-month survival rate was 29 {\%} (95 {\%} CI 18-41 {\%}) and the median progression-free survival was 2 months. Fifteen patients survived 6 months or more. Two patients had objective partial responses, and 28 {\%} of patients had stable disease. Changes in biomarkers including soluble VEGF and vascular endothelial growth factor receptor did not correlate with response to drug. Conclusion: Vatalanib was well tolerated as a second-line therapy and resulted in favorable 6-month survival rate in patients with metastatic pancreatic cancer, compared with historic controls.",
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T1 - Phase II trial of vatalanib in patients with advanced or metastatic pancreatic adenocarcinoma after first-line gemcitabine therapy (PCRT O4-001)

AU - Dragovich, T.

AU - Laheru, Daniel

AU - Dayyani, F.

AU - Bolejack, V.

AU - Smith, L.

AU - Seng, J.

AU - Burris, H.

AU - Rosen, P.

AU - Hidalgo, M.

AU - Ritch, P.

AU - Baker, A. F.

AU - Raghunand, N.

AU - Crowley, J.

AU - Von Hoff, D. D.

PY - 2014

Y1 - 2014

N2 - Purpose: Vatalanib (PTK 787/ZK22584) is an oral poly-tyrosine kinase inhibitor with strong affinity for platelet-derived growth factor and vascular endothelial growth factor (VEGF) receptors. We conducted an open-label, phase II multicenter therapeutic trial investigating the efficacy and tolerability of vatalanib in patients with metastatic or advanced pancreatic cancer who failed first-line gemcitabine-based therapy. Methods: Vatalanib treatment consisted of a twice daily oral dosing using a "ramp-up schedule," beginning with 250 mg bid during week 1,500 mg bid during week 2, and 750 mg bid on week three and thereafter. The primary objective of this study was to evaluate the 6-month survival rate. Results: Sixty-seven patients were enrolled. The median age was 64, and 66 % (N = 43) had only one prior regimen. Common grade 3/4 adverse events included hypertension (20 %; N = 13), fatigue (17 %; N = 11), abdominal pain (17 %; N = 11), and elevated alkaline phosphatase (15 %; N = 10). Among the 65 evaluable patients, the 6-month survival rate was 29 % (95 % CI 18-41 %) and the median progression-free survival was 2 months. Fifteen patients survived 6 months or more. Two patients had objective partial responses, and 28 % of patients had stable disease. Changes in biomarkers including soluble VEGF and vascular endothelial growth factor receptor did not correlate with response to drug. Conclusion: Vatalanib was well tolerated as a second-line therapy and resulted in favorable 6-month survival rate in patients with metastatic pancreatic cancer, compared with historic controls.

AB - Purpose: Vatalanib (PTK 787/ZK22584) is an oral poly-tyrosine kinase inhibitor with strong affinity for platelet-derived growth factor and vascular endothelial growth factor (VEGF) receptors. We conducted an open-label, phase II multicenter therapeutic trial investigating the efficacy and tolerability of vatalanib in patients with metastatic or advanced pancreatic cancer who failed first-line gemcitabine-based therapy. Methods: Vatalanib treatment consisted of a twice daily oral dosing using a "ramp-up schedule," beginning with 250 mg bid during week 1,500 mg bid during week 2, and 750 mg bid on week three and thereafter. The primary objective of this study was to evaluate the 6-month survival rate. Results: Sixty-seven patients were enrolled. The median age was 64, and 66 % (N = 43) had only one prior regimen. Common grade 3/4 adverse events included hypertension (20 %; N = 13), fatigue (17 %; N = 11), abdominal pain (17 %; N = 11), and elevated alkaline phosphatase (15 %; N = 10). Among the 65 evaluable patients, the 6-month survival rate was 29 % (95 % CI 18-41 %) and the median progression-free survival was 2 months. Fifteen patients survived 6 months or more. Two patients had objective partial responses, and 28 % of patients had stable disease. Changes in biomarkers including soluble VEGF and vascular endothelial growth factor receptor did not correlate with response to drug. Conclusion: Vatalanib was well tolerated as a second-line therapy and resulted in favorable 6-month survival rate in patients with metastatic pancreatic cancer, compared with historic controls.

KW - Pancreatic adenocarcinoma

KW - Second-line treatment

KW - Tyrosine kinase inhibitor

KW - Vatalinib

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