Author of

• 12592

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  P3.10 - Poster Session 3 - Chemotherapy (ID 210)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12612

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    P3.10-020 - Phase I and Pharmacokinetic Study of Erlotinib Administered in Combination With Amrubicin in Patients With Previously Treated, Advanced Non-Small Cell Lung Cancer (ID 1403)

    09:30 - 09:30  |  Author(s): M. Kubota
    • Abstract

    Background
    Standard second-line chemotherapy against advanced non-small-cell lung cancer (NSCLC) is a single agent such as docetaxel, pemetrexed, or erlotinib. The response rate of each agent as second-line setting are from 10% to 15% in Japanese NSCLC without EGFR mutation. Amrubicin, a totally synthetic 9-aminoanthracycline, is active as second-line chemotherapy for advanced NSCLC. The reported response rate to amrubicin as second-line treatment for advanced NSCLC is 11.5%. Erlotinib is an orally active reversible inhibitor of epidermal growth factor receptor tyrosine kinase activity (EGFR-TKI), which induces rapid tumor shrinkage if the tumor harbors EGFR activated mutation. Erlotinib is also effective for NSCLC without EGFR mutation, but the response rate is around 8%. We considered it worthwhile to explore if a doublet regimen consisting of amrubicin and erlotinib may provide therapeutic benefit and have a favorable toxicity profile. We performed the growth inhibition assay for NSCLC cell lines and made two-dimension isobolograms to estimate the synergy of the combination. The combination of amrubicin and erlotinib had significant synergistic effect on EGFR wild type NSCLC cell line A549, and additive effect on EGFR mutant cell line PC-9. We conducted a phase I trial of this combination. The aim was to determine the maximum tolerated dose (MTD), the dose-limiting toxicities (DLTs) and pharmacokinetics of this combination in patients with non-small cell lung cancer (NSCLC) who had previous chemotherapy.

    Methods
    Nine patients with stage IV disease were treated at 3-week intervals with erlotinib once daily on days 1-21 plus amrubicin 5-min intravenous injection on days 1-3.

    Results
    The dose levels evaluated were erlotinib (mg/day)/amrubicin (mg/m[2]): 100/30 (n = 3), 100/35 (n = 3) and 150/30 (n = 3). The MTD of erlotinib and amrubicin was 100 mg/day and 35 mg/m[2] since two of the three patients experienced DLTs during the first cycle of treatment at the third dose level of 150 mg/day and 30 mg/m[2]. Cessation of erlotinib administration for 8 days due to grade 3 leukopenia and grade 3 skin infection (erysipelas) were the DLTs. No drug-drug interactions between erlotinib and amrubicin were observed in this study. The overall response rate was 33%, including three partial responses, in the nine patients. The median progression-free survival for all patients was extraordinary long 11.3 months, and the median overall survival has not yet been reached.

    Conclusion
    Combined erlotinib plus amrubicin therapy seems to be highly effective, with acceptable toxicity, against NSCLC. The recommended dose for phase II studies was erlotinib 100 mg once daily on days 1-21, and amrubicin 35 mg/m[2] on days 1-3 administered every 21 days.