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
Study type: Interventional
Phase: Phase 3

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 .
    

Detailed description: 
      Nowadays,EGFR mutation status is unknown for most of the advanced NSCLC patients in clinical
      practice.Those patients with high probability of EGFR mutation maybe could get benefit from
      gefitinib as first-line treatment. For this reason, the investigators need more investigation
      to focus on EGFR mutation unknown patients. In the previous study (including FAST-ACT), the
      patients enrolled trial received EGFR-TKI plus chemotherapy nearly simultaneously,so the
      investigators could not know whether those patients gained benefit from EGFR-TKI or
      chemotherapy, maybe chemotherapy alone was enough. If the patients with EGFR mutation status
      unknown could get stable disease(SD) after two cycles of chemotherapy,those patients may be
      optimal for the investigation of intercalating and maintenance administration of gefitinib.
      The reasons are that chemotherapy may be enough for those with objective response after two
      cycles chemotherapy, of course, those with disease progression (PD) should be excluded from
      the study.

      On the basis of these and other studies, the investigators hypothesized that in a selected
      population,first-line chemotherapy(gemcitabine +carboplatin) with intercalating and
      maintenance use of gefitinib would be more efficacious than chemotherapy alone. In this
      study, the investigators compared the efficacy, safety, and adverse-event profile of
      chemotherapy plus gefitinib with those of chemotherapy alone, when these drugs were used as
      first-line treatment in nonsmokers or former light smokers in China, who had lung
      adenocarcinoma with EGFR gene mutation unknown.
    

Intervention name(s): Gefitinib; Gemcitabine +Carboplatin
Intervention type(s): Drug; Drug
Intervention description(s): 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
Other intervention name(s): Iressa
Intervention MeSH terms: Carboplatin; Gemcitabine; Gefitinib
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: chemotherapy; maintenance therapy; gefitinib