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

David Ferry, Lucinda Billingham, Hugh Jarrett, David Dunlop, Penella J Woll, Marianne Nicolson, Riyaz Shah, Joyce Thompson, James Spicer, D Muthukumar, Geraldine Skailes, Pauline Leonard, A D Chetiyawardana, Paula Wells, Conrad Lewanski, Barbara Crosse, Michelle Hill, Piers Gaunt, Kenneth O'Byrne

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Abstract

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.

Original languageEnglish
Pages (from-to)302-312
Number of pages11
JournalEuropean Journal of Cancer
Volume83
Early online date4 Aug 2017
DOIs
Publication statusPublished - Sep 2017

Keywords

  • Non-small-cell lung cancer
  • Carboplatin
  • Cisplatin
  • Gemcitabine
  • Randomised phase III trial
  • Quality of life

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