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B.D.W. Harris
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P2.03a - Poster Session with Presenters Present (ID 464)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03a-015 - Systemic Inflammation Alters Carboplatin Pharmacokinetics Explaining Poor Survival in Advanced Lung Cancer Patients (ID 4986)
14:30 - 14:30 | Author(s): B.D.W. Harris
- Abstract
Background:
Advanced cancer patients with elevated systemic inflammatory markers have significantly poorer chemotherapy response and shorter overall survival compared to patients without inflammation. However, mechanisms underlying this association are unclear. There is an urgent need to identify these mechanisms as a high proportion of advanced cancer patients present with systemic inflammation (~25%). This study aimed to determine the impact of inflammatory status, as determined by the neutrophil-to-lymphocyte ratio (NLR), on drug pharmacokinetics and clinical outcomes, including patient toxicity, chemotherapy cycles received, response and survival, in patients with advanced non-small cell lung cancer (NSCLC).
Methods:
Seventy-two advanced NSCLC patients were recruited for a planned 6 cycles of carboplatin (target AUC 6 mg/mL•min) and paclitaxel (175mg/m[2]) chemotherapy. Drug concentrations from the first chemotherapy cycle were measured and analysed using population pharmacokinetic modelling. Clinical data and pharmacodynamic endpoints were also collected. Univariate analysis and multivariable regression analysis was used to identify relationship between NLR status (NLR ≤ 5 and NLR > 5) to pharmacokinetic parameters and clinical outcomes.
Results:
Patient demographics were not different between low and high NLR groups except for nutritional status. Patients with NLR > 5 had increased carboplatin exposure but no associations were found with paclitaxel pharmacokinetics. Increased carboplatin exposure associated with increased toxicities. Patients with elevated inflammation had serious clinical consequences including dose-limiting toxicities leading to reduced cycles of first-line chemotherapy, poor response and shorter overall survival.
Conclusion:
Advanced NSCLC patients with elevated inflammation have alterations in drug pharmacokinetics that may be negatively impacting their clinical outcomes. This under-appreciated inflammatory-mediated change in pharmacokinetics is a potential source of inter-individual variability that may be reduced by dose individualisation according to inflammatory status. Future trials of this approach need to be investigated to assess the impact on survival in advanced cancer populations treated with platinum-based chemotherapy.
