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  P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)

  • Event: WCLC 2015
  • Type: Poster
  • Track: Treatment of Advanced Diseases - NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)

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    P3.01-086 - A Phase I Dose-Escalation Study of Pirfenidone Combined with Standard First-Line Chemotherapy in Advanced-Stage Lung NSCLC (ID 712)

    09:30 - 09:30  |  Author(s): M.L. Freeman-Keller
    • Abstract
    • Slides

    Background:
    Approximately 1.6 million people are diagnosed with lung cancer annually, of which 85% of cases are NSCLC. Due to limited efficacy of current conventional chemotherapy, the majority of patients face poor prognosis; thus, combining chemotherapy with agents targeting the tumor microenvironment may be a novel approach to improving survival outcomes. Pirfenidone (5-methyl-1-phenyl-1H-pyridine-one), an agent demonstrating activity against fibroblasts and growth-promoting cytokines (TGF-β1, fibroblast growth factor [FGF], epidermal growth factor [EGF], and platelet-derived growth factor [PDGF]), has demonstrated clinical efficacy in IPF but has not yet been studied in lung cancer. We propose a proof-of-concept trial testing a novel combination of pirfenidone plus standard first-line chemotherapy in the treatment of advanced-stage NSCLC. Pirfenidone Pirfenidone has demonstrated activity against growth-promoting cytokines such as TGF-β1, FGF, EGF, and PDGF. A recent Phase III clinical trial of pirfenidone compared to placebo in patients with IPF demonstrated improved lung function, exercise tolerance, and progression-free survival (PFS) with an acceptable side-effect profile. To date, pirfenidone has not been studied in cancer, but its anti-fibroblast properties may play an important role in the tumor microenvironment. Our hypothesis is that pirfenidone (by targeting CAFs) in combination with standard chemotherapy will act synergistically and proffer a more potent strategy for NSCLC treatment. Data Generated in Dr Antonia’s Lab at Moffitt Cancer Center Using low doses of pirfenidone (0.5 mg/ml), we observed a small decrease in cell proliferation (20%), also noted with low doses of cisplatin (10%). When both drugs were used, we observed a synergistic decline in proliferation (60%). An in vivo model was performed to verify this data: nude mice were inoculated with a combination of A549 cells and CAF cells at a 1:1 ratio. Treatment with pirfenidone and cisplatin began as soon as tumors were palpable. Cisplatin- or pirfenidone-treated mice had a larger tumor size than mice treated with the combination, and on the final day (43 days after start of treatment), the combination showed statistically significant improvement compared to controls. This led to our hypothesis that similar tumor regression may occur in NSCLC patients.Figure 1
    
    
    
    Methods:
    Phase I, single-center, dose-escalation study. Phase I trial, followed by an expansion of 20 pts with non-squamous and 10 pts with squamous cell lung cancer. Primary Objectives: Determine safety, tolerability, and MTD of pirfenidone plus chemotherapy in pts with advanced NSCLC, and obtain the preliminary ORR. Secondary Objectives: Determine OS and PFS of pts treated with pirfenidone plus standard first-line chemotherapy.
    
    Results:
    Not applicable
    
    Conclusion:
    Not applicable
    
    

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