Phase II trial of vatalanib in patients with advanced or metastatic pancreatic adenocarcinoma after first-line gemcitabine therapy (PCRT O4-001). Cancer Chemother Pharmacol 2014 Aug;74(2):379-87
Date
06/19/2014Pubmed ID
24939212Pubmed Central ID
PMC4461053DOI
10.1007/s00280-014-2499-4Scopus ID
2-s2.0-84907597082 (requires institutional sign-in at Scopus site) 59 CitationsAbstract
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.
Author List
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 DDMESH terms used to index this publication - Major topics in bold
AdenocarcinomaAdult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Biomarkers, Tumor
Deoxycytidine
Enzyme-Linked Immunosorbent Assay
Female
Follow-Up Studies
Humans
Male
Middle Aged
Neoplasm Metastasis
Neoplasm Recurrence, Local
Neoplasm Staging
Pancreatic Neoplasms
Phthalazines
Prognosis
Pyridines
Survival Rate
