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

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.

• Authors: G D'Addario, D Rauch, R Stupp, M Pless, R Stahel, N Mach, L Jost, L Widmer, C Tapia, M Bihl, M Mayer, K Ribi, S Lerch, L Bubendorf, D C Betticher
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 19 Issue 4 Pg. 739-45 (Apr 2008) ISSN: 1569-8041 [Electronic] England
• PMID: 18096565 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• Adult
• Aged
• Aged, 80 and over
• Analysis of Variance
• Antineoplastic Agents (adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (diagnostic imaging, drug therapy, etiology, pathology)
• Cisplatin (administration & dosage)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Disease Progression
• Drug Administration Schedule
• ErbB Receptors (genetics)
• Female
• Gefitinib
• Humans
• In Situ Hybridization, Fluorescence
• Kaplan-Meier Estimate
• Lung Neoplasms (diagnostic imaging, drug therapy, etiology, 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)
• Gemcitabine