Surgery, Gemcitabine, Cisplatin, and Radiation Therapy in Treating Patients With Stage II or Stage III Non-Small Cell Lung Cancer

City of Hope

Status and phase

Terminated

Phase 2

Conditions

Lung Cancer

Treatments

Radiation: radiation therapy

Genetic: reverse transcriptase-polymerase chain reaction

Genetic: gene expression analysis

Other: immunohistochemistry staining method

Procedure: adjuvant therapy

Drug: gemcitabine hydrochloride

Procedure: conventional surgery

Drug: cisplatin

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00530634

CHNMC-99077

CDR0000564760 (Registry Identifier)

P30CA033572 (U.S. NIH Grant/Contract)

99077

Details and patient eligibility

About

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.

Full description

OBJECTIVES:

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.

Enrollment

3 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed single, primary bronchogenic non-small cell lung cancer meeting the following subtypes:
- Adenocarcinoma (no bronchioalveolar cell histology)
- Squamous cell carcinoma
- Large cell carcinoma
Meeting the following staging criteria:
- Stage IIB (T2, N1, M0, or T3, N0, M0)
- Stage IIIA (T1-3, N2, M0 or T3, N1, M0)
- Stage IIIB (Any T, N3, M0 or T4, Any N, M0)
No more than 1 parenchymal lesion in the same lung or in both lungs
No tumor involving the superior sulcus (e.g., Pancoast tumor)
Patients must undergo evaluation by the involved thoracic surgeon, medical oncologist, and radiation oncologist prior to registration
No evidence of metastatic disease
- Biopsy or aspiration cytology required to confirm the benign diagnosis of CT or MRI abnormalities that potentially represent metastatic disease
- Biopsy required if all noninvasive tests are indeterminant

PATIENT CHARACTERISTICS:

Karnofsky performance status 70-100%
Absolute granulocyte count ≥ 1,500/μL
Platelet count ≥ 100,000/μL
Bilirubin ≤ 3 times upper limit of normal (ULN)
SGOT and SGPT ≤ 3 times ULN
Creatinine clearance > 50 mL/min
No prior malignancy except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, ductal or lobular carcinoma in situ of the breast, or any other cancer from which the patient has been disease-free for 5 years
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective protection
No significant hearing loss or patient unwilling to accept potential for further hearing loss
No uncontrolled medical illness by appropriate medical therapy (e.g., myocardial infarction within the past 3 months or liver cirrhosis)
No symptomatic peripheral neuropathy affecting activities of daily living

PRIOR CONCURRENT THERAPY:

No prior chemotherapy or radiotherapy for lung cancer

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

3 participants in 1 patient group

Gemcitabine + Cisplatin

Experimental group

Description:

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.

Treatment: