Phase II study of dovitinib in patients with metastatic and/or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib

Abstract

Background:This prospective, phase II trial evaluated the efficacy and safety of dovitinib in patients with metastatic and/or unresectable gastrointestinal stromal tumours (GISTs) after failure of at least imatinib and sunitinib.Methods:Patients received oral dovitinib, 500 mg once daily, for 5 consecutive days, followed by a 2-day rest, every 28 days. The primary endpoint was disease control rate (DCR; objective response+stable disease (SD)) at 24 weeks, assessed by computed tomography (CT) scan according to RECIST v1.0. Metabolic response was evaluated by positron emission tomography (PET)–CT scans performed at baseline and after 4 weeks of treatment.Results:Between September 2011 and April 2012, 30 patients were enroled. DCR at 24 weeks by RECIST v1.0 was 13% and one patient (3%) had a partial response. Based on the European Organization for Research and Treatment of Cancer PET response criteria, four patients (13%) had a metabolic partial response after 4 weeks of treatment. At a median follow-up of 8.3 months (range, 6.3–12.2 months), median progression-free survival (PFS) was 3.6 months (95% confidence interval (CI), 3.5–3.7 months) and median overall survival was 9.7 months (95% CI, 6.0–13.4 months). Metabolic progressive disease at Week 4 was significantly associated with shorter PFS (P=0.03). Grade 3/4 adverse events included asthenia (20%), neutropenia (13%), thrombocytopenia (10%), and hypertriglyceridaemia (10%). Most toxicities were manageable by dose modification.Conclusion:Dovitinib showed modest antitumour activity with manageable toxicities in heavily pretreated patients with advanced GISTs.

Phase 2 trial of dovitinib in patients with progressive FGFR3-mutated or FGFR3 wild-type advanced urothelial carcinoma

“…Hypertension was observed in six (14%) patients. Overall, the dovitinib safety profile was consistent with previous reports on other indications and with other anti-VEGFR targeted therapies [14,21]. Although the most common treatment-associated AEs in this study occurred less frequently than previously reported for patients with metastatic renal cell carcinoma (RCC), [21] this finding may reflect the shorter median duration of exposure (7.5 weeks in this study versus 14.3 weeks in the RCC study).…”

“…Serum dovitinib concentrations after the 500-mg dose (14-453 ng/mL) were in the expected range [13,14]. Nearly all statistically significant mean fold-changes from baseline in serum biomarker levels with treatment occurred in the FGFR3 WT group, including increases in PlGF and VEGF and decreases in sVEGFR2 and CKIT (Table A.1; Fig.…”

Incidence, Diagnosis, and Management of QT Prolongation Induced by Cancer Therapies: A Systematic Review

“…QTc prolongation was common (37%) in patients with hepatic impairment treated with bosutinib,10 but this was not seen in other smaller studies 11, 12. QTc prolongation was infrequent or absent with afatinib, crizotinib, ceritinib, dovitinib, imatinib, lapatinib, lenvatinib, nintedanib, pazopanib, and ponatinib 9, 14, 16, 17, 19, 24, 26, 27, 29, 30, 31, 32, 33, 35, 36, 38, 39, 72, 78, 81, 161, 162, 163, 164…”

The role of dietary polyphenols in the moderation of the inflammatory response in early stage colorectal cancer

“…Studies have shown that aspirin may suppress cancer cell growth by blocking the PI3K pathway and inducing apoptosis (Uddin et al, 2010). Furthermore, regular aspirin use after diagnosis of colorectal cancer was associated with longer survival in those patients with mutated PIK3CA colorectal cancer (Kang et al, 2013).…”