title: Sunitinib (SU11248) in patients with chemo naive extensive small cell lung cancer or who have a 'chemosensitive' relapse: A single-arm phase II study (EORTC-08061).
abstract: BACKGROUND
  Targeted therapies have to date not been successful in the treatment of small cell lung cancer (SCLC). This study aimed to assess the therapeutic activity of sunitinib (an oral, multi-targeted tyrosine kinase inhibitor) using positron emission tomography (PET)-computed tomography (CT) imaging as an early indicator of response.
  
  
  METHODS
  This was a single-arm phase II study of sunitinib in patients with SCLC who are either chemo naive (extensive disease) or have a 'sensitive' relapse. A loading dose of 150 mg sunitinib was given orally followed by 37.5 mg/d. The primary end-point was disease control rate (DCR) at 8 weeks after the start of treatment and secondary end-points included toxicity of treatment and overall response. PET-CT was carried out at 4 weeks into the treatment. The study was closed early because of low accrual with only 9 of required 48 patients (19%) accrued.
  
  
  RESULTS
  Nine patients were registered, seven females and two males with a median age of 65 years and a median duration of sunitinib treatment of 7.4 weeks. DCR at 8 weeks was achieved in two patients, both of whom went on to long periods of disease control, one patient achieved a partial response which lasted 10 months and a second patient had stable disease (minor shrinkage) which lasted 20 months. One of these patients proved to have an atypical carcinoid tumour at rebiopsy after 10 months. DCR and PET-CT imaging both predicted these responses. Grade III-IV toxicities were encountered during treatment, most commonly neutropenia (n = 3), thrombocytopenia (n = 3) and hypermagnesaemia (n = 2). One toxic death occurred due to bronchial haemorrhage.
  
  
  CONCLUSIONS
  This study emphasises the need for alternate study design and end-points for new drug assessment in SCLC. EudraCT number: 2006-002485-19.
authors.affiliation: Royal Marsden NHS Foundation Trust, London, United Kingdom; Clinical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Fatma
authors.initials: F
authors.lastname: Abdelraouf
authors.affiliation: Dept. Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands; Dept. Pulmonary Diseases, Vrije Universiteit VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Egbert
authors.initials: E
authors.lastname: Smit
authors.affiliation: EORTC Headquarters, Brussels, Belgium.
authors.forename: Baktiar
authors.initials: B
authors.lastname: Hasan
authors.affiliation: EORTC Headquarters, Brussels, Belgium.
authors.forename: Jessica
authors.initials: J
authors.lastname: Menis
authors.affiliation: Royal Marsden NHS Foundation Trust, London, United Kingdom; Heart and Lung Institute, Imperial College London, United Kingdom.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Popat
authors.affiliation: Thoracic Oncology, University Hospital Antwerp, Belgium; Thoracic Oncology, University Hospital Ghent, Belgium.
authors.forename: Jan P
authors.initials: JP
authors.lastname: van Meerbeeck
authors.affiliation: Thoracic Oncology, University Hospital Ghent, Belgium.
authors.forename: Veerle F
authors.initials: VF
authors.lastname: Surmont
authors.affiliation: Dept. Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Baas
authors.affiliation: Royal Marsden NHS Foundation Trust, London, United Kingdom. Electronic address: mary.obrien@rmh.nhs.uk.
authors.forename: Mary
authors.initials: M
authors.lastname: O'Brien
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004334:Drug Administration Schedule; D057239:Early Termination of Clinical Trials; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D009364:Neoplasm Recurrence, Local; D018579:Patient Selection; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D018401:Sample Size; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000473:pathology; D000077210:Sunitinib; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D000077210:Sunitinib
keywords: Phase II study; SCLC; Second-line treatment; Sunitinib; Targeted therapy; Tyrosine kinase inhibitor