Fatma Abdelraouf1, Egbert Smit2, Baktiar Hasan3, Jessica Menis3, Sanjay Popat4, Jan P van Meerbeeck5, Veerle F Surmont6, Paul Baas7, Mary O'Brien8. 1. Royal Marsden NHS Foundation Trust, London, United Kingdom; Clinical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt. 2. Dept. Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands; Dept. Pulmonary Diseases, Vrije Universiteit VU Medical Center, Amsterdam, The Netherlands. 3. EORTC Headquarters, Brussels, Belgium. 4. Royal Marsden NHS Foundation Trust, London, United Kingdom; Heart and Lung Institute, Imperial College London, United Kingdom. 5. Thoracic Oncology, University Hospital Antwerp, Belgium; Thoracic Oncology, University Hospital Ghent, Belgium. 6. Thoracic Oncology, University Hospital Ghent, Belgium. 7. Dept. Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. 8. Royal Marsden NHS Foundation Trust, London, United Kingdom. Electronic address: mary.obrien@rmh.nhs.uk.
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. CONCLUSION: This study emphasises the need for alternate study design and end-points for new drug assessment in SCLC. EudraCT number: 2006-002485-19.
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. CONCLUSION: This study emphasises the need for alternate study design and end-points for new drug assessment in SCLC. EudraCT number: 2006-002485-19.
Authors: Paul A Bunn; John D Minna; Alexander Augustyn; Adi F Gazdar; Youcef Ouadah; Mark A Krasnow; Anton Berns; Elisabeth Brambilla; Natasha Rekhtman; Pierre P Massion; Matthew Niederst; Martin Peifer; Jun Yokota; Ramaswamy Govindan; John T Poirier; Lauren A Byers; Murry W Wynes; David G McFadden; David MacPherson; Christine L Hann; Anna F Farago; Caroline Dive; Beverly A Teicher; Craig D Peacock; Jane E Johnson; Melanie H Cobb; Hans-Guido Wendel; David Spigel; Julien Sage; Ping Yang; M Catherine Pietanza; Lee M Krug; John Heymach; Peter Ujhazy; Caicun Zhou; Koichi Goto; Afshin Dowlati; Camilla Laulund Christensen; Keunchil Park; Lawrence H Einhorn; Martin J Edelman; Giuseppe Giaccone; David E Gerber; Ravi Salgia; Taofeek Owonikoko; Shakun Malik; Niki Karachaliou; David R Gandara; Ben J Slotman; Fiona Blackhall; Glenwood Goss; Roman Thomas; Charles M Rudin; Fred R Hirsch Journal: J Thorac Oncol Date: 2016-01-30 Impact factor: 15.609
Authors: Xuetian Gao; Ling Peng; Li Zhang; Kai Huang; Cuihua Yi; Bei Li; Xue Meng; Jisheng Li Journal: J Cancer Res Clin Oncol Date: 2021-11-08 Impact factor: 4.322