fostamatinib and Kidney-Neoplasms

A multi-cohort phase II study of fostamatinib, an oral multi-kinase inhibitor, was conducted to determine the response rate in patients with advanced colorectal (CRC), thyroid, non-small cell lung, head and neck, and renal cell carcinomas, and pheochromocytomas.. Patients received 200 mg fostamatinib BID in 4-week cycles with response assessed every 2 cycles. Blood was collected for pharmacokinetic analysis and measurements of circulating tumor cells and circulating endothelial (progenitor) cells (CE(P)Cs).. A total of 37 patients (22 CRC), median of 4 prior therapies, were enrolled. Due to toxicities in four of the first five patients, the study was amended to incorporate a dose escalation phase for each histology. The maximum-tolerated dose was established at 50 mg BID in CRC but was not established for the other cancers. Common grade 3/4 toxicities included transaminitis, hyperbilirubinemia, and hypertension. Pharmacokinetic profile was similar to previous reports. Seventy-three percent of CRC patients had liver involvement and 91 % had prior anti-angiogenic therapy. Patients with abnormal liver tests at baseline were more likely to experience grade ≥ 2 hepatotoxicity than those with normal tests (44 vs. 0 %). No responses were observed; disease stabilization rate was 27 % in CRC. Reduction in CECs following treatment was associated with a better disease stabilization rate (75 vs. 0 %) in CRC.. Fostamatinib had limited anti-tumor activity in this first clinical trial in patients with advanced refractory solid tumors; reduction in CECs and CEPs was indicative of anti-angiogenic effects. Abnormal liver testing at baseline appeared to influence drug tolerability.

Topics: Adrenal Gland Neoplasms; Adult; Aged; Aged, 80 and over; Aminopyridines; Carcinoma, Non-Small-Cell Lung; Carcinoma, Renal Cell; Cohort Studies; Colorectal Neoplasms; Endothelial Cells; Female; Head and Neck Neoplasms; Humans; Kidney Neoplasms; Lung Neoplasms; Male; Middle Aged; Morpholines; Neoplasms; Oxazines; Pheochromocytoma; Protein Kinase Inhibitors; Pyridines; Pyrimidines; Thyroid Neoplasms