Article
Effect of food on the pharmacokinetics of sunitinib malate (SU11248), a multi-targeted receptor tyrosine kinase inhibitor: results from a phase I study in healthy subjects.
Department of Clinical Pharmacology, Pfizer Global Research and Development, La Jolla, California 92121, USA.
Anti-Cancer Drugs (impact factor:
2.41).
04/2006;
17(3):353-8.
Source: PubMed
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Citations (0)
- Cited In (6)
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Article: Phase II study of sunitinib as second-line treatment for advanced gastric cancer.
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ABSTRACT: This phase II, open-label, multicenter study assessed the oral, multitargeted, tyrosine kinase inhibitor sunitinib in patients with advanced gastric or gastroesophageal junction adenocarcinoma who had received prior chemotherapy. Patients received sunitinib 50 mg/day on Schedule 4/2 (4 weeks on treatment, followed by 2 weeks off treatment). The primary endpoint was objective response rate; secondary endpoints included clinical benefit rate, duration of response, progression-free survival (PFS), overall survival (OS), pharmacokinetics, pharmacodynamics, safety and tolerability, and quality of life. Of 78 patients enrolled, most had gastric adenocarcinoma (93.6%) and metastatic disease (93.6%). All were evaluable for safety and efficacy. Two patients (2.6%) had partial responses and 25 patients (32.1%) had a best response of stable disease for ≥6 weeks. Median PFS was 2.3 months (95% confidence interval [CI], 1.6-2.6 months) and median OS was 6.8 months (95% CI, 4.4-9.6 months). Grade ≥ 3 thrombocytopenia and neutropenia were reported in 34.6% and 29.4% of patients, respectively, and the most common non-hematologic adverse events were fatigue, anorexia, nausea, diarrhea, and stomatitis. Pharmacokinetics of sunitinib and its active metabolite were consistent with previous reports. There were no marked associations between baseline soluble protein levels, or changes from baseline, and measures of clinical outcome. The progression-delaying effect and manageable toxicity observed with sunitinib in this study suggest that although single-agent sunitinib has insufficient clinical value as second-line treatment for advanced gastric cancer, its role in combination with chemotherapy merits further study.Investigational New Drugs 05/2010; 29(6):1449-58. · 3.36 Impact Factor -
Article: Phase I and pharmacokinetic study of sunitinib in pediatric patients with refractory solid tumors: a children's oncology group study.
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ABSTRACT: Sunitinib is an oral multitargeted receptor tyrosine kinase inhibitor. The purpose of this study was to determine the recommended phase 2 dose, pharmacokinetics, pharmacodynamic effects, and preliminary antitumor activity of sunitinib in a pediatric population. Patients who were 2 to 21 years of age with refractory solid tumors were eligible if they had measurable or evaluable disease and met baseline organ function requirements. Patients received sunitinib once daily for 28 days followed by a 14-day break between each cycle. Dose levels of 15 and 20 mg/m(2)/d were evaluated, with dose escalation based on a 3 + 3 design. Sunitinib pharmacokinetics and biomarkers of angiogenesis were also evaluated during the first cycle. Twenty-three patients were treated (median age 13.9 years; range, 3.9-20.6 years). The most common toxicities were neutropenia, thrombocytopenia, elevated liver transaminases, gastrointestinal symptoms, and fatigue. Two patients developed dose-limiting reductions in cardiac ejection fraction prompting a protocol amendment to exclude patients with previous exposure to anthracyclines or cardiac radiation. In patients without these cardiac risk factors, the maximum tolerated dose (MTD) was 15 mg/m(2)/d. Steady-state plasma concentrations were reached by day 7. No objective responses were observed. Four patients with sarcoma and glioma had stable disease for 2 to 9 cycles. Cardiac toxicity precluded determination of a recommended dose for pediatric patients with previous anthracycline or cardiac radiation exposure. The MTD of sunitinib for patients without risk factors for cardiac toxicity is 15 mg/m(2)/d for 28 days followed by a 14-day break.Clinical Cancer Research 06/2011; 17(15):5113-22. · 7.74 Impact Factor -
Article: Use of virtual patient populations for rescuing discontinued drug candidates and for reducing the number of patients in clinical trials.
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ABSTRACT: The decreasing cost-efficiency of drug development threatens to result in a severe shortage of innovative drugs, which may seriously compromise patient healthcare. This risk underlines the urgency to change the paradigm in clinical research. Here, we examine a novel concept of conducting virtual clinical trials for efficiently screening drug candidates, and for evaluating their prospects of being brought to the market successfully. The virtual clinical trials are carried out by using virtual patients (denoted Optimata Virtual Patients -- OVPs). The OVP, a set of mathematical algorithms that describe the main pathological and physiological dynamic processes affected by the administered drug, has been shown to accurately predict docetaxel efficacy and safety in individual breast cancer patients. We report a test case in which virtual clinical trials have been conducted by using OVP populations for rescuing a discontinued oncology compound, ISIS-5132 (ISIS Pharmaceuticals Inc.). Our in silico study suggested that ISIS-5132 may be efficacious in combination with another drug, sunitinib malate (Sutent, Pfizer Inc.), for the treatment of prostate cancer. The recommended combined treatment is predicted to result in a higher five-year Progression-Free Survival than monotherapy with either drug alone.Alternatives to laboratory animals: ATLA 09/2009; 37 Suppl 1:39-45. · 1.58 Impact Factor
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Keywords
10-h fast
16 healthy subjects
active metabolite SU12662
AUC
AUC0-infinity
AUC0-last
CIs
Cmax
fasted state
fed state
food effect
formation/absorption
high-calorie meal
multi-targeted tyrosine kinase inhibitor
oral
oral bioavailability
randomized open-label
ratios
two-way crossover study
