An open-label phase II study evaluating the safety and efficacy of PTK787 in patients with progressive metastatic neuroendocrine cancer

Abstract

14124 Background: PTK787, an aminophthalazine, is an orally active angiogenesis inhibitor blocking all known vascular endothelial growth factor receptors (VEGFR)- and platelet-derived growth factor receptor (PDGFR)-tyrosine kinases . The majority of metastatic neuroendocrine malignancies express VEGF and PDGF receptors. Since both growth factors have been implicated in tumor-induced angiogenesis, PTK787 offers a novel approach for inhibiting tumor growth. Methods: In a phase II trial, we investigated the safety and antitumor activity of PTK787 in patients who had biopsy-proven metastatic neuroendocrine cancer, such as carcinoid, and had shown evidence of progression on somatosatin analog therapy. Eligible patients had measurable lesions other than bone, a Karnofsky performance status >60 and normal hematologic, renal and hepatic functions. Patients on octreotide therapy were required to be on a stable dose not exceeding 30 mg monthly of the LAR formulation. Initial dosing of PTK787 was 1,250 mg daily. Results: Six patients (4 males) were enrolled between 5/20/05 to 8/09/05. Median age was 61 years (range, 48 to 65). There was 1 withdrawal of consent. The remaining 5 patients continue on treatment as of January 2006. One patient required a 10 day discontinuation for rising SGOT/SGPT and alkaline phosphatase. Resumption of PTK787 at 1,000 mg daily was well tolerated in this patient. Radiographically and scintigraphically, all 5 patients have demonstrated stable disease by CT and OctreoScan, respectively. Recruitment to this trial continues. Conclusions: PTK787 is generally well tolerated in patients with metastatic neuroendocrine cancer and may be effective in controlling somatostatin analog resistant disease though partial radiographic responses have not been observed. No significant financial relationships to disclose.