Author of

• 10743

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  P1.10 - Poster Session 1 - Chemotherapy (ID 204)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10772

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    P1.10-029 - An analysis of the drug-drug interaction between docetaxel and gefitinib in patients with advanced non-small cell lung cancer (ID 1564)

    09:30 - 09:30  |  Author(s): Y. Hayashi
    • Abstract

    Background
    Both Docetaxel (DTX) and Gefitinib (Gef) have been established as a standard therapy for the treatment of non-small cell lung cancer (NSCLC). Since these active two agents have different mechanisms of action as well as toxicity profiles, the combined use of DTX and Gef could be highly effective for the advanced NSCLC. However, as they are both metabolized by cytchrome P450 (mainly CYP3A4) enzyme, there are concerns about drug-drug interactions. The aim of this study is to assess the influence by the combined use of Gef on DTX's pharmacokinetics (PKs) and toxicity in patients with advanced NSCLC.

    Methods
    DTX was intravenously administered over 1-hr every 3 weeks on day 1. Gef (250-mg) was co-administrated orally once daily from day 2. The dose of DTX was escalated from 45 mg/m[2] (level 1, n = 6) to 60 mg/m[2] (level 2, n = 6). The total of 20-point PK samplings were performed on day 1 (DTX alone) and day 22 (DTX + Gef) to measure plasma concentrations of DTX using high- performance liquid chromatography (HPLC). DTX PK profile was estimated by non-compartment analysis. Analysis of variance was performed on AUC~0-24h~ to estimate adjusted mean differences between day 1 and 22. DTX clearance (CL), geometric mean (GM) of AUC, adjusted GM ratio (GMR, i.e., the ratio of DTX AUC on day 22 to that in day 1) and 90% CI of the GMR were also calculated.

    Results
    Twelve patients with advanced NSCLC were enrolled. Two out of 12 patients at dose level 1 withheld the second cycle of treatment (i.e., on day 22) due to progressive disease, and DTX PKs data were available for the rest of 10 patients treated on day 1 and 22. The toxicity profiles of DTX and Gef in this study were generally acceptable, and frequency and severity of hematological toxicity possibly related to DTX were similar to those with historical data in Japanese NSCLC patients. The ≥ grade 3 neutropenia was observed in 66% of patients. GMs of AUC~0-24 ~on day 1 and 22 were 1128 and 1184 ng・h /ml at dose level 1 (n=4), while those were 1827 and 1630 ng・h /ml at dose level 2 (n=6). GMs of DTX CL in all patients on day 1 and 22 were 60 and 63 L/h and GMRs at dose level 1 and 2 were 1.05 (90%CI: 0.96-1.14) and 0.89 (90%CI: 0.82-0.97), respectively.

    Conclusion
    The above results demonstrate that DTX PKs is not affected by the combined use of Gef in patients with advanced NSCLC. These two active agents can be safely co-administered.