{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:03:53Z","timestamp":1791576233893,"version":"4.3.4"},"reference-count":34,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2006,1,1]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> To establish the safety, pharmacokinetics, and recommended dose of sunitinib, a novel oral multitargeting tyrosine kinase inhibitor with antiangiogenic and antitumor properties, in patients with advanced malignancies. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Sunitinib was given orally for 4 weeks every 6 weeks. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Twenty-eight patients received doses ranging from 15 to 59 mg\/m<jats:sup>2<\/jats:sup> (ranging from 50 mg every other day to 150 mg\/d). Dose-limiting toxicities reported at the maximum-tolerated doses \u2265 75 mg\/d were reversible grade 3 fatigue, grade 3 hypertension, and grade 2 bullous skin toxicity. Therefore, the recommended dose was 50 mg\/d. At this dose, the main adverse effects were sore mouth, edema, and thrombocytopenia. Hair discoloration and yellow coloration of the skin were observed at doses \u2265 50 mg\/d. Pharmacokinetic data indicate that potentially active target plasma concentrations \u2265 50 ng\/mL can be achieved with moderate interpatient variability and a long half-life compatible with a single daily dosing. Six objective responses were observed in three renal cell carcinomas, one neuroendocrine tumor, one stromal tumor, and one unknown primary adenocarcinoma patient. At higher doses (\u2265 75 mg\/d), tumor responses were often associated with reduced intratumoral vascularization and central tumor necrosis, eventually resulting in organ perforation or fistula. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> At the dose of 50 mg\/d (4 weeks on, 2 weeks off), sunitinib displays manageable toxicity. Antitumor activity supports further studies in patients with renal cell carcinoma, gastrointestinal, neuroendocrine, and stromal tumors. Future studies may consider including prospective imaging techniques such as high frequency ultrasound to monitor tumor density. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2005.02.2194","type":"journal-article","created":{"date-parts":[[2005,11,29]],"date-time":"2005-11-29T01:34:26Z","timestamp":1133228066000},"page":"25-35","source":"Crossref","is-referenced-by-count":992,"title":["Safety, Pharmacokinetic, and Antitumor Activity of SU11248, a Novel Oral Multitarget Tyrosine Kinase Inhibitor, in Patients With Cancer"],"prefix":"10.1200","volume":"24","author":[{"given":"Sandrine","family":"Faivre","sequence":"first","affiliation":[{"name":"From the Department of Medicine, Gustave-Roussy Institute, Villejuif, France; and SU11248 Working Group, Pfizer Co, Rome, Italy and New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Delbaldo","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave-Roussy Institute, Villejuif, France; and SU11248 Working Group, Pfizer Co, Rome, Italy and New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Vera","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave-Roussy Institute, Villejuif, France; and SU11248 Working Group, Pfizer Co, Rome, Italy and New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Robert","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave-Roussy Institute, Villejuif, France; and SU11248 Working Group, Pfizer Co, Rome, Italy and New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Lozahic","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave-Roussy Institute, Villejuif, France; and SU11248 Working Group, Pfizer Co, Rome, Italy and New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Lassau","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave-Roussy Institute, Villejuif, France; and SU11248 Working Group, Pfizer Co, Rome, Italy and New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Bello","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave-Roussy Institute, Villejuif, France; and SU11248 Working Group, Pfizer Co, Rome, Italy and New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Deprimo","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave-Roussy Institute, Villejuif, France; and SU11248 Working Group, Pfizer Co, Rome, Italy and New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Brega","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave-Roussy Institute, Villejuif, France; and SU11248 Working Group, Pfizer Co, Rome, Italy and New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Massimini","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave-Roussy Institute, Villejuif, France; and SU11248 Working Group, Pfizer Co, Rome, Italy and New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Armand","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave-Roussy Institute, Villejuif, France; and SU11248 Working Group, Pfizer Co, Rome, Italy and New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Scigalla","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave-Roussy Institute, Villejuif, France; and SU11248 Working Group, Pfizer Co, Rome, Italy and New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Raymond","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave-Roussy Institute, Villejuif, France; and SU11248 Working Group, Pfizer Co, Rome, Italy and New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc905"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1381"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1038\/nm988"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021491"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200317929"},{"key":"R6","unstructured":"Shaheen RM, Tseng WW, Davis DW, et al: Tyrosine kinase inhibition of multiple angiogenic growth factor receptors improves survival in mice bearing colon cancer liver metastases by inhibition of endothelial cell survival mechanisms. 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