Influence of Prior Chemotherapy on Clinical Benefit With Erlotinib in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer With or Without EGFR Gene Mutation
Condition: Advanced Non-Squamous Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Study type: Interventional
Phase: Phase 2

Summary: 
      To compare the differential influence of 1st line doublet chemotherapy containing Docetaxel
      versus Pemetrexed on clinical efficacy of Erlotinib as a second line therapy in patients with
      relapsed or progressed non-squamous NSCLC.
    

Detailed description: 
      The clinical management of advanced non-small cell lung cancer (NSCLC) remains challenging.
      Initial therapies for advanced NSCLC with platinum-based regimens have shown consistent
      overall response rates of 30% to 40% with progression-free intervals of 4-5 months and 1-year
      survival rates of 35% to 40% [1-3]. First line doublet chemotherapy commonly used in daily
      practice includes Gemcitabine, vinorelbine, paclitaxel and docetaxel those have proven
      efficacy with platinum against best supportive care, prolonging survival for approximately 3
      months. Recently, pemetrexed, a multi-target antifolate agent, has been introduced into the
      1st line doublet chemotherapy with platinum-based regimen to have similar efficacy and a
      better safety profile compared to docetaxel or gemcitabine [4]. Although those agents seem to
      have equivalent efficacy, tolerability tends to be a concern for docetoxel.

      Myelosuppression with the standard docetaxel schedule of 75 mg/m2 administered once every 3
      weeks is extremely frequent and severe; neutropenia occurs in 54% to 67% of patients and
      febrile neutropenia occurs in 1.8% to 8.0% of patients [5, 6]. Moreover, non-hematologic
      toxicities, such as grade 3-4 asthenia (12% to 18%), and nausea and vomiting (1% to 3.6%),
      are not uncommon [5, 6]. To increase tolerability of docetaxel, alternative schedules have
      been extensively studied. Accumulating evidence suggests that a weekly schedule of docetaxel
      (35 mg/m2) reduces severe and febrile neutropenia without decreasing antitumor activity
      [7-10]. Nevertheless, no significant differences were observed for anemia, thrombocytopenia,
      and non-hematologic toxicity [7]. For the same reason, a lower dose of docetaxel (60 mg/m2
      every 3 weeks) has been recommended in Japan [11, 12]. However, recent large scale trials
      with such a dose of docetaxel still revealed high incidences of grade 3 and 4 neutropenia (up
      to 82.9%) [12-14]. Different schedules of low dose docetaxel have not been studied, nor has a
      comparison been made between low dose docetaxel and the less toxic agent, pemetrexed.

      Currently, the investigators have been following a schedule of weekly low dose docetaxel (30
      mg/m2 on days 1 and 8 every 3 weeks; 60 mg/m2 accumulated dose for each cycle) at our
      hospital in an effort to achieve better tolerability (in press-chemotherapy 2010). The
      investigators therefore perform an exploratory study, by prospective analysis, to investigate
      the efficacy and toxicity of such a low dose docetaxel schedule compared to that of
      pemetrexed in patients with NSCLC who are chemotherapy naive.

      Erlotinib, an orally-available epidermal growth factor receptor (EGFR) tyrosine-kinase
      inhibitor (TKI), significantly prolongs survival and produces significant symptom and
      quality-of-life benefits compared with best supportive care in unselected patients with
      relapsed non-small-cell lung cancer (NSCLC) [15, 16]. In a large, phase III,
      placebo-controlled study (BR.21), erlotinib produced a survival benefit across all patient
      sub-groups studied [15].
    

Intervention name(s): Docetaxel/cisplatin; Pemetrexed/cisplatin
Intervention type(s): Drug; Drug
Intervention description(s): The treatment schedule comprises a maximum of six 3-week treatment cycles consisting of weekly docetaxel (30 mg/m2) and cisplatin (37.5 mg/m2) for 2 consecutive weeks followed by a 1-week treatment-free period. The patients will be assessed after each cycle and a final assessment will be done after three and six cycles.; The patients are given pemetrexed (500 mg/m2 as a 10-min intravenous infusion) and cisplatin (75 mg/m2) on day 1 every 21 days. Dexamethasone (4 mg) is administered twice daily on the day before, the day of, and the day after each dose of pemetrexed. Oral folic acid supplementation (1000 mg) is administered daily, beginning approximately 2 weeks prior to the first dose of pemetrexed and continues until 3 weeks after treatment discontinuation. A 1000 mg vitamin B12 injection is administered intramuscularly approximately 1-2 weeks before the first dose of pemetrexed and is repeated approximately every 9 weeks until 3 weeks after therapy discontinuation.
Other intervention name(s): Taxotere- made by Sanofi-Aventis.; Alimta- made by LiLy.
Intervention MeSH terms: Cisplatin; Docetaxel; Pemetrexed
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment