title: A phase II study of sunitinib in patients with recurrent and/or metastatic non-nasopharyngeal head and neck cancer.
abstract: OBJECTIVE
  Patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN) bear a grave prognosis. There are unmet needs for the development of novel agents for this incurable disease. Angiogenesis is an important biological process in SCCHN. We, therefore, evaluated the activity and safety of sunitinib, an oral tyrosine kinase inhibitor that targets multiple receptors, in patients with RM-SCCHN.
  
  
  METHODS
  Seventeen patients were treated with sunitinib 50 mg per day administrated in 4-week cycles followed by a rest period of 2 weeks. Sunitinib and SU012662 plasma levels were determined based on a validated liquid chromatography-tandem mass spectrometry method and pharmacokinetic data were fitted in a non-compartmental analysis.
  
  
  RESULTS
  Totally, 28 6-week cycles of treatment with sunitinib were administered (median, 2 cycles). Only three patients demonstrated stabilization of the disease; therefore, the study had to be terminated prematurely due to futility. Grade 3 toxicities, apart from fatigue, were infrequent. Other frequently reported side effects were skin discoloration, neutropenia, and thrombocytopenia. Ten various bleeding complications were reported in seven patients. Mean maximum concentrations (C(max)) were reached during the first day of treatment for sunitinib at 38.98 (+ or - 22.66) ng/ml and for SU012662 at 11.12 (+ or - 24.57) ng/ml. Our results showed that SU012662 has a longer half-life and a larger volume of distribution than the parent drug sunitinib. None of the biological markers tested was of any prognostic value.
  
  
  CONCLUSIONS
  According to our findings, sunitinib monotherapy was not proven active in RM-SCCHN, and no further development of the drug in this indication is warranted.
authors: Department of Medical Oncology, "Papageorgiou" Hospital, Aristotle University of Thessaloniki School of Medicine, 564 03, Thessaloniki, Macedonia, Greece. fountzil@auth.gr
authors: George
authors: G
authors: Fountzilas
authors: Anna
authors: A
authors: Fragkoulidi
authors: Anna
authors: A
authors: Kalogera-Fountzila
authors: Martha
authors: M
authors: Nikolaidou
authors: Mattheos
authors: M
authors: Bobos
authors: Julien
authors: J
authors: Calderaro
authors: Felipe
authors: F
authors: Andreiuolo
authors: Marios
authors: M
authors: Marselos
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000855:Anorexia / Q000139:chemically induced; D019540:Area Under Curve; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D007211:Indoles / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011758:Pyrroles / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077210:Sunitinib; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007211:Indoles; D011758:Pyrroles; C544393:SU 12662; D042461:Vascular Endothelial Growth Factor A; D000077210:Sunitinib