Surgery, Gemcitabine, Cisplatin, and Radiation Therapy in Treating Patients With Stage II or Stage III Non-Small Cell Lung Cancer
RATIONALE: Drugs used in chemotherapy, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with radiation therapy after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase II trial is studying how well surgery followed by gemcitabine, cisplatin, and radiation therapy works in treating patients with stage II or stage III non-small cell lung cancer.
Drug: gemcitabine hydrochloride
Genetic: gene expression analysis
Genetic: reverse transcriptase-polymerase chain reaction
Other: immunohistochemistry staining method
Procedure: adjuvant therapy
Procedure: conventional surgery
Radiation: radiation therapy
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Multimodality Therapy for Stages II and III Non-Small Cell Lung Cancer: Surgical Resection Followed by Sequential Administration of Gemcitabine Plus Cisplatin Chemotherapy and Radiation Therapy|
- Two-year Progression-free Survival From the Date of Surgery [ Time Frame: 2 years post-surgery ] [ Designated as safety issue: No ]Estimated using the product-limit method of Kaplan and Meier. Progression defined as a 25% increase or an increase of 10 cm2 (whichever is smaller) in the sum of the products of all measurable lesions over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline, or clear worsening of any evaluable disease, or reappearance of any lesion that had disappeared, or appearance of any new lesion/site, or failure to return for evaluation or death, or deteriorating condition (unless clearly unrelated to this cancer).
|Study Start Date:||August 1999|
|Study Completion Date:||June 2013|
|Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
Experimental: Gemcitabine + Cisplatin
Surgical resection followed by (within 60 days) by chemotherapy (Gemcitabine at 1000 mg/m2 IV over 30 minutes on days 1 and 8 of a 21 day cycle and Cisplatin at 75 mg/m2 IV over 1 hour on day 8 of a 21 day cycle) followed by radiation therapy (treated using linear accelerator with photon beam energy of 6-21 MV) upon completion of 3 cycles of chemotherapy.
|Drug: cisplatin Drug: gemcitabine hydrochloride Genetic: gene expression analysis Genetic: reverse transcriptase-polymerase chain reaction Other: immunohistochemistry staining method Procedure: adjuvant therapy Procedure: conventional surgery Radiation: radiation therapy|
- To assess overall survival and progression-free survival of patients with stage II-IIIB non-small cell lung cancer undergoing surgical resection, followed by adjuvant chemotherapy comprising gemcitabine and cisplatin, and radiotherapy.
- To assess the toxicities of this regimen in these patients.
- To evaluate the mRNA expression of enzymes (i.e., excision repair cross complementing protein, ribonucleotide reductase, and cytidine/deoxycytidine deaminase and kinase), which may be important in regulating the cytotoxicity of gemcitabine and cisplatin in patient tumors.
- To correlate mRNA levels with progression-free survival of patients treated with this regimen.
- To assess BCL2, P53, and HER2-neu expression by IHC and correlation with progression-free survival.
OUTLINE: Patients undergo surgical resection of their tumor and mediastinal lymph node dissection. Patients with complete surgical eradication of their disease or pathologic evidence of microscopic residual disease proceed to adjuvant chemotherapy.
Within approximately 60 days after surgical resection, patients receive adjuvant chemotherapy comprising gemcitabine IV over 30 minutes on days 1 and 8 and cisplatin IV over 1 hour on day 8. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Beginning 130-144 days after surgery, patients undergo radiotherapy once daily, five days a week, for approximately 6 weeks.
Tumor tissue specimens are obtained at the time of surgical resection for pharmacodynamic and biomarker correlative studies. Specimens are examined by reverse transcriptase-polymerase chain reaction to measure mRNA expression of target oncogenes (i.e., DNA repair gene ERCC-1 and M2 subunit of the DNA repair gene ribonucleotide reductase) and enzymes (i.e., cytidine/deoxycytidine deaminase and kinase). Resected specimens are also assessed by IHC for the expression of BCL2, P53, and HER2-neu genes.
After completion of study therapy, patients are followed every 6 months for 5 years and annually thereafter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00530634
|Principal Investigator:||Marianna Koczywas, MD||Beckman Research Institute|