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

  • 12600

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    P3.10-008 - A phase I study evaluating the continuation of gefitinib beyond progressive disease followed by the addition of docetaxel (ID 891)

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

    Background
    Despite the high disease control rate in EGFR-mutated patients, gefitinib treatment is not curative and eventually there is disease progression. Recent studies report that discontinuation of EGFR-TKIs result in rapid disease progression in NSCLC patients who had developed acquired resistance. These findings suggest that patients with acquired resistance could have sensitive and resistant tumor clones to EGFR-TKIs. We designed a phase I trial to assess the safety and efficacy of docetaxel combined with gefitinib in NSCLC patients who acquired resistance.

    Methods
    Patients with metastatic NSCLC who had responded to gefitinib treatment and then developed progressive disease were treated with docetaxel in combination with the continuation of gefitinib. Docetaxel was administered on day 1 of 21-day cycle and escalated from 50 to 70 mg/m[2]. Gefitinib was given at a fixed dose of 250mg/day. Dose limiting toxicities (DLT) were assessed after the first cycle, and doses were escalated in 3 to 6 patient cohorts.

    Results
    Fourteen patients were treated at doses of 50 (n=4), 60 (n=5) and 70 mg/m[2] (n=5). All 14 patients were evaluable for safety and efficacy. At a docetaxel dose of 60 mg/m[2], 1 patient experienced a DLT (grade 4 neutropenia for 4 days), and at a dose of 70 mg/m[2] 1 patient experienced a DLT (grade 4 neutropenia for 4 days and febrile neutropenia). Because all 5 patients treated at a docetaxel dose of 70 mg/m[2] had grade 4 neutropenia, this dose level was determined to be the maximum-tolerated dose. The overall response rate was 43%, median progression free survival was 183 days (95% CI, 157 to 215 days), and median overall survival was 575 days (95% CI, 220 to 816 days). At the recommended dose of 60 mg/m[2], the overall response rate was 40%.

    Conclusion
    Recommended dose of docetaxel is 60 mg/m[2] in combination with gefitinib. This combination was well tolerated and demonstrated activity in NSCLC patients with acquired resistance to gefitinib.