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A. Fujita



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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.10-018 - An administration timing and dosage of the gefitinib in the advanced non-small-cell lung cancer patients with epidermal growth factor receptor mutation (ID 1380)

      09:30 - 09:30  |  Author(s): A. Fujita

      • Abstract

      Background
      In the patients who had locally advanced or metastatic non-small-cell lung cancer with epidermal growth factor receptor (EGFR) mutation, progression-free survival (PFS) was prolonged by first line therapy of gefitinib than those of chemotherapy. However, overall survival (OS) was not prolonged due to the crossover administration of tyrosine kinase inhibitor. In such patients, the administration timing of gefitinib becomes a clinically interesting issue. Moreover, it is unknown whether effect of gefitinib was attenuated or not by alternate-day administration for the adverse effects such as exanthema, diarrhea, and liver function disorder. The suitable dosage of gefitinib to the patients with EGFR mutation is thought to be actually unidentified, because of the setting dosage before proving the EGFR mutation. Therefore, we retrospectively analyzed the population of patients receiving gefitinib at our hospital to solve these questions and examine the prognostic factors in the patients with EGFR mutations.

      Methods
      Eighty three patients (median age 66 years, 51 females), except ten patients with combined chemotherapy, have begun to be received gefitinib in our hospital between January 1, 2007 and December 31, 2012. These data were collected at May 31, 2013 and analyzed using Cox proportion hazard model with covariance which may influence OS and PFS of gefitinib therapy. These patients were composed of 3 negative, 34 unknown, and 46 positive patients with EGFR mutations. The median follow-up time was 7 months, ranging 1 to 141 months. The median OS was 34 months in all patients (n=83) and 43 months in the patients with EGFR mutation in exon19 or exon21 (n=44). The median PFS was 11 months in the former and 19 months in the latter.

      Results
      As previously reported, the factors such as female (hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.26 to 0.81, P=0.007) or smoker (HR 2.55, 95%CI 1.46 to 4.47, P=0.001) influenced PFS in all patients. However, they did not in the patients with EGFR mutation. As for the administration timing of the gefitinib, the later starting date of its administration (HR 0.97, 95%CI 0.94 to 1.00, P=0.02) slightly improved the OS in all patients, which might be influenced by other factors, because the later therapy line (HR 1.55, 95%CI 1.17 to 2.05, P=0.002) worsened PFS. Its administration timing did not significantly influence OS or PFS in the patients with EGFR mutations. As for the dosage of gefitinb, the increase of body surface area significantly influenced PFS in the all patients (HR 7.12, 95%CI 1.05 to 49.1, P=0.045). Paradoxically, the prolonged administration intervals improved OS (HR 0.39, 95%CI 0.20 to 0.76, P=0.006) and PFS (HR 0.35, 95%CI 0.19 to 0.65, P=0.001) in all patients and PFS (HR 0.34, 95%CI 0.14 to 0.83, P=0.018) in the patients with EGFR mutations.

      Conclusion
      In summary, the administration timing did not influence OS or PFS in the patients with EGFR mutations. Moreover, the alternate-day administration might not decrease the effect on the patients with EGFR mutations. Given the adverse effects, the provision of appropriate dosage is required for these patients.