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)

Eur J Cancer. 2016 Feb:54:35-39. doi: 10.1016/j.ejca.2015.10.016. Epub 2015 Dec 21.

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.

Keywords: Phase II study; SCLC; Second-line treatment; Sunitinib; Targeted therapy; Tyrosine kinase inhibitor.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Disease Progression
  • Drug Administration Schedule
  • Early Termination of Clinical Trials
  • Female
  • Humans
  • Indoles / adverse effects
  • Indoles / therapeutic use*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Multimodal Imaging
  • Neoplasm Recurrence, Local*
  • Patient Selection
  • Positron-Emission Tomography
  • Predictive Value of Tests
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrroles / adverse effects
  • Pyrroles / therapeutic use*
  • Sample Size
  • Small Cell Lung Carcinoma / drug therapy*
  • Small Cell Lung Carcinoma / pathology
  • Sunitinib
  • Time Factors
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Indoles
  • Protein Kinase Inhibitors
  • Pyrroles
  • Sunitinib