Gemcitabine and Cisplatin in Treating Patients With Stage I Non-Small Cell Lung Cancer That Was Removed by Surgery

OBJECTIVES:

Primary

- To assess the feasibility of assigning adjuvant treatment based on tumoral RRM1 and
ERCC1 gene expression in patients with complete surgical resection of stage IA (≥ 2 cm)
or IB non-small cell lung cancer.

Secondary

- To estimate the collective 2-year disease-free survival of these patients.

- To assess the frequency and severity of toxicities resulting from the administration of
cisplatin and gemcitabine hydrochloride.

- To explore, preliminarily, the relationship between RNA and protein expression of RRM1
and ERCC1, and the relationship between RRM1 and ERCC1 expression in the formalin-fixed
and paraffin-embedded tumor specimens, and to generate results on in situ protein
expression and other assays for genes involved in drug efficacy.

- To assess the analytical performance of the biomarker assay.

OUTLINE: This is a multicenter study.

Patients are assigned to 1 of 2 treatment arms based on RRM1 and ERCC1 gene expression.

- Arm I (RRM1 ≥ 40 and ERCC1 ≥ 65): Patients undergo active monitoring after surgery with
disease assessments at 8, 16, and 24 weeks.

- Arm II (RRM1 < 40 and/or ERCC1 < 65): Beginning within 84 days after surgery, patients
receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV
over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 courses in the
absence of disease progression or unacceptable toxicity.

Tumor samples acquired at the time of surgery are analyzed by immunofluorescence-based
automated quantitative analysis for in situ expression of RRM1 and ERCC1. If available,
additional samples are assessed using RT-PCR and real-time quantitative PCR for RRM1 and
ERCC1 expression levels; polymorphism analysis for RRM1 and ERCC1 expression at the protein
level; and tissue microarray analysis of genes associated with DNA synthesis, damage repair,
and drug efficacy.

After completion of study therapy, patients are followed every 6 months for up to 2 years.