Multicenter phase II trial of gefitinib first-line therapy followed by chemotherapy in advanced non-small-cell lung cancer (NSCLC): SAKK protocol 19/03

Ann Oncol. 2008 Apr;19(4):739-45. doi: 10.1093/annonc/mdm564. Epub 2007 Dec 19.

Abstract

Background: Gefitinib is active in patients with pretreated non-small-cell lung cancer (NSCLC). We evaluated the activity and toxicity of gefitinib first-line treatment in advanced NSCLC followed by chemotherapy at disease progression.

Patients and methods: In all, 63 patients with chemotherapy-naive stage IIIB/IV NSCLC received gefitinib 250 mg/day. At disease progression, gefitinib was replaced by cisplatin 80 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1, 8 for up to six 3-week cycles. Primary end point was the disease stabilization rate (DSR) after 12 weeks of gefitinib.

Results: After 12 weeks of gefitinib, the DSR was 24% and the response rate (RR) was 8%. Median time to progression (TtP) was 2.5 months and median overall survival (OS) 11.5 months. Never smokers (n = 9) had a DSR of 56% and a median OS of 20.2 months; patients with epidermal growth factor receptor (EGFR) mutation (n = 4) had a DSR of 75% and the median OS was not reached after the follow-up of 21.6 months. In all, 41 patients received chemotherapy with an overall RR of 34%, DSR of 71% and median TtP of 6.7 months.

Conclusions: First-line gefitinib monotherapy led to a DSR of 24% at 12 weeks in an unselected patients population. Never smokers and patients with EGFR mutations tend to have a better outcome; hence, further trials in selected patients are warranted.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / etiology
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cisplatin / administration & dosage
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease Progression
  • Drug Administration Schedule
  • ErbB Receptors / genetics
  • Female
  • Gefitinib
  • Gemcitabine
  • Humans
  • In Situ Hybridization, Fluorescence
  • Kaplan-Meier Estimate
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / etiology
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Staging
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Quality of Life
  • Quinazolines / therapeutic use*
  • Radiography
  • Risk Assessment
  • Risk Factors
  • Smoking / adverse effects
  • Surveys and Questionnaires
  • Switzerland
  • Treatment Outcome
  • ras Proteins / genetics

Substances

  • Antineoplastic Agents
  • KRAS protein, human
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Quinazolines
  • Deoxycytidine
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins
  • Cisplatin
  • Gefitinib
  • Gemcitabine