Carboplatin versus two doses of cisplatin in combination with gemcitabine in the treatment of advanced non-small-cell lung cancer: Results from a British Thoracic Oncology Group randomised phase III trial
Research output: Contribution to journal › Article
- Royal Wolverhampton NHS Trust
- Beatson West Scotland Cancer Centre, Glasgow G12 0YN, UK.
- University of Sheffield
- Aberdeen Royal Infirmary, Ward 111, Aberdeen, UK
- Kent Oncology Centre, Maidstone Hospital, Maidstone, UK.
- Renal Department, Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UK. email@example.com
- King's College London
- Department of Radiology, Colchester Hospital University NHS Foundation Trust, Colchester General Hospital, Turner Road, Colchester, Essex, CO4 5JL, UK.
- Royal Preston Hospital Lancashire Teaching Hospitals NHS Foundation Trust
- Whittington Health NHS Trust, Whittington Hospital, London, UK.
- Queen Elizabeth Hospital Birmingham, Queen Elizabeth Medical Centre
- Pharmacy Department, Barts Heart Centre, Barts Health NHS Trust, London, UK
- Imperial College/Imperial Healthcare NHS Trust, Charing Cross Hospital, 1st Floor, E Wing, Fulham Palace Road, London, W6 8RF, UK; and at the Division of Cancer, ICTEM Hammersmith Campus, Du Cane Road London W12 0NN, UK.
- St James' Hospital, Dublin, Ireland.
- Calderdale and Huddersfield NHS Foundation Trust, Huddersfield, UK
BACKGROUND: Platinum-based combination chemotherapy is standard treatment for the majority of patients with advanced non-small-cell lung cancer (NSCLC). The trial investigates the importance of the choice of platinum agent and dose of cisplatin in relation to patient outcomes.
METHODS: The three-arm randomised phase III trial assigned patients with chemo-naïve stage IIIB/IV NSCLC in a 1:1:1 ratio to receive gemcitabine 1250 mg/m(2) on days 1 and 8 of a 3-week cycle with cisplatin 80 mg/m(2) (GC80) or cisplatin 50 mg/m(2) (GC50) or carboplatin AUC6 (GCb6) for a maximum of four cycles. Primary outcome measure was survival time, aiming to test for a difference between treatment arms and also assess non-inferiority with pre-defined margin selected as hazard ratio (HR) of 1.2. Secondary outcome measures included response rate, adverse events and quality of life (QoL).
FINDINGS: The trial recruited 1363 patients. Survival time differed significantly across the three treatment arms (p = 0.046) with GC50 worst with median 8.2 months compared to 9.5 for GC80 and 10.0 for GCb6. HRs (adjusted) for GC50 compared to GC80 was 1.13 (95% confidence interval [CI] 0.99-1.29) and for GC50 compared to GCb6 was 1.23 (95% CI: 1.08-1.41). GCb6 was significantly non-inferior to GC80 (HR = 0.93, upper limit of one-sided 95% CI 1.04). Adjusting for QoL did not change the findings. Best objective response rates were 29% (GC80), 20% (GC50) and 27% (GCb6), p < 0.007. There were more dose reductions and treatment delays in the GCb6 arm and more adverse events (60% with at least one grade 3-4 compared to 43% GC80 and 30% GC50).
INTERPRETATION: In combination with gemcitabine, carboplatin at AUC6 is not inferior to cisplatin at 80 mg/m(2) in terms of survival. Carboplatin was associated with more adverse events and not with better quality of life. Cisplatin at the lower dose of 50 mg/m(2) has worse survival which is not compensated by better quality of life. CLINICALTRIALS.
GOV IDENTIFIER: NCT00112710.
EUDRACT NUMBER: 2004-003868-30.
CANCER RESEARCH UK TRIAL IDENTIFIER: CRUK/04/009.
|Number of pages||11|
|Journal||European Journal of Cancer|
|Early online date||4 Aug 2017|
|Publication status||Published - Sep 2017|
- Non-small-cell lung cancer, Carboplatin, Cisplatin, Gemcitabine, Randomised phase III trial, Quality of life