Intercalating and Maintenance Use of Iressa Versus Chemotherapy in Selected Advanced Non Small Cell Lung Cancer
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Gefitinib; Gemcitabine +Carboplatin
Intervention description: Gefitinib 250mg/d every cycle d15-25,and Gefitinib 250mg/d from d15 of last cycle until disease progression; Gemcitabine 1250mg/m2+Carboplatin AUC=5, every 4 weeks, maximum 4 cycles
Intervention MeSH terms: Carboplatin; Gemcitabine; Gefitinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 219.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: chemotherapy; maintenance therapy; gefitinib

Summary:

      Platinum-based combination chemotherapy, such as gemcitabine-carboplatin, is one of the
      standard first-line therapy for advanced non-small cell lung cancer (NSCLC).

      Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) have clinical
      efficacy, as compared with the best supportive care or standard chemotherapy, when given as
      second-line or third-line therapy for advanced NSCLC.

      Treatment with EGFR-TKI is most effective in female, never-smoker, or patients with
      adenocarcinoma, and patients of Asian origin. In these populations, such treatment is
      associated with favorable objective response rates, progression-free survival, and overall
      survival. These populations also have a relatively high incidence of somatic mutations in the
      region of the EGFR gene that encodes the tyrosine kinase domain.

      The recent study(IPASS) by Tony S. Mok showed gefitinib was superior to
      carboplatin-paclitaxel as an initial treatment for pulmonary adenocarcinoma among nonsmokers
      or former light smokers in East Asia . In the subgroup of 261 patients who were positive for
      the EGFR gene mutation, PFS was significantly longer among those who received gefitinib than
      among those who received carboplatin-paclitaxel(HR= 0.48,P<0.001), whereas in the subgroup of
      176 patients who were negative for the mutation, PFS was significantly longer among those who
      received carboplatin-paclitaxel(HR=2.85,P<0.001). Gefitinib treatment was well tolerated,
      with lower in hematologic toxicity, and no treatment-related interstitial lung disease.In
      this study(IPASS), only patients with a mutation of the EGFR gene in the tumor could get
      benefit from gefitinib as first line treatment.

      Tony S. Mok and his colleague also found that intercalating and maintenance administration of
      erlotinib(another EGFR-TKI)following gemcitabine/platinum chemotherapy as first line therapy
      led to a significant improvement in PFS .
    

Eligibility criteria:

        Inclusion Criteria:

          -  After two cycles chemotherapy(gemcitabine plus carboplatin), patients with stable
             disease(SD) by RECIST1.1.

          -  Patients between 18 and 75 years of age.

          -  Present with histologically proven or cytological diagnosis of adenocarcinoma NSCLC
             Stage IIIB or IV as defined by the American Joint Committee on Cancer Staging Criteria
             for Lung Cancer, that is not amenable to curative therapy,such as surgery or
             radiotherapy and so on.

          -  No prior systemic chemotherapy or targeted therapy for lung cancer before screening.

          -  Never smokers(defined as having smoked less than 100 cigarettes in their lifetime ) or
             light ex-smokers (defined as having ceased smoking at least 15 years before Day 1 of
             study treatment and having smoked 10 pack-years or fewer).

          -  EGFR mutation status unknown.

          -  ECOG performance status of 0 or 1.

          -  Adequate organ function.

          -  Prior radiation therapy allowed to <25% of the bone marrow . Prior radiation to the
             whole pelvis is not allowed. Prior radiotherapy must be completed at least 4 weeks
             before study enrollment. Patients must have recovered from the acute toxic effects of
             the treatment prior to study enrollment.

          -  Signed informed consent document on file.

          -  Estimated life expectancy of ≥12 weeks.

          -  Patient compliance and geographic proximity that allow adequate follow up.

        Exclusion Criteria:

          -  Known severe hypersensitivity to gefitinib.

          -  Sympotomatic patients with brain metastases.

          -  Pleural effusion or pericardiac effusion that cannot be controlled by drainage or
             other procedures.

          -  Inability to comply with protocol or study procedures.

          -  A serious concomitant systemic disorder that, in the opinion of the investigator,
             would compromise the patient's ability to complete the study.

          -  A serious cardiac condition, such as myocardial infarction within 6 months, angina, or
             heart disease.

          -  Second primary malignancy that is clinically detectable at the time of consideration
             for study enrollment.

          -  Interstitial pneumonia.