Neoadjuvant Chemoradiotherapy Followed By Surgery in Treating Patients With Limited-Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy such as irinotecan and cisplatin use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Irinotecan and cisplatin may also make the tumor cells more sensitive to radiation therapy. Combining chemotherapy with radiation therapy before surgery may shrink the tumor so that it can be removed during surgery. PURPOSE: This phase I trial is studying the side effects of neoadjuvant radiation therapy given together with irinotecan and cisplatin followed by surgery in treating patients with limited-stage small cell lung cancer.

Detailed Description
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OBJECTIVES: Determine the safety and feasibility of neoadjuvant chemoradiotherapy with irinotecan and cisplatin followed by surgery in patients with limited stage small cell lung cancer. Determine the pathologic complete response rate of patients treated with this regimen. Correlate the level of vascular endothelial growth factor with treatment response and disease outcome in patients treated with this regimen. Correlate genetic polymorphisms in cytochrome P450 1A1, glutathione S-transferase M1 and P1, myeloperoxidase, and NAD(p)H: quinone oxidoreductase with treatment response and disease outcome in patients treated with this regimen. OUTLINE: This is a pilot study. Induction chemotherapy: Patients receive cisplatin IV over 1 hour on day 1 and irinotecan IV over 90 minutes on days 1 and 8. Chemoradiotherapy: Beginning on day 21, patients receive chemoradiotherapy comprising radiotherapy once daily, 5 days a week for 4 weeks and then twice daily for 4 days. Patients also receive cisplatin IV and irinotecan IV over 30-60 minutes once weekly concurrently with radiotherapy. Treatment continues in the absence of disease progression or unacceptable toxicity. At the completion of chemoradiotherapy, patients are evaluated for surgery. Patients who are candidates for surgery receive one additional course of cisplatin IV and irinotecan IV. Patients who are not candidates for surgery receive radiotherapy twice daily for 4 days and cisplatin IV and irinotecan IV as in chemoradiotherapy. Surgery: Approximately 2-4 weeks after the last dose of chemotherapy, patients undergo surgery. Patients are followed every 4 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Official Title
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Phase I Study of Preoperative Chemo/Radiation (Concurrent Irinotecan/Cisplatin/RT) Followed by Surgery in Limited Stage Small Cell Lung Cancer (SCLC-LS)

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: irinotecan hydrochloride
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed small cell lung cancer Limited stage disease (clinical stage I-IIIA) and meets the following criteria: Confined to 1 hemithorax No T4 disease based on malignant pleural effusion No N3 disease based on contralateral hilar or supraclavicular involvement Contralateral mediastinal (N3) nodes greater than 1.5 cm on CT scan must be biopsied to rule out pathologic involvement Measurable or evaluable disease Tumor must be able to be encompassed by limited radiotherapy field without significantly compromising pulmonary function No pleural effusion visible on chest x-ray (regardless of cytology) No prior complete tumor resection PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 70-100% Life expectancy Not specified Hematopoietic Absolute granulocyte count at least 1,800/mm^3 Platelet count at least 100,000/mm^3 Hepatic Bilirubin no greater than 1.5 mg/dL No known Gilbert's disease Renal Creatinine no greater than 1.5 mg/dL Calcium less than 12.0 mg/dL Cardiovascular No myocardial infarction within the past 6 months No congestive heart failure No uncontrolled arrhythmias No active unstable angina Pulmonary Calculated postoperative FEV_1 at least 800 cc No chronic obstructive pulmonary disease with FEV_1 no greater than 1 L or uncontrolled bronchospasm in the unaffected lung Other Not pregnant Negative pregnancy test Fertile patients must use effective contraception No other malignancy within the past 2 years except curatively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or any other noninvasive malignancy No history of seizures No history of uncontrolled psychiatric illness that would preclude giving informed consent or complying with study No active or uncontrolled infection No uncontrolled diabetes mellitus (random blood sugar at least 250 mg/dL) No other concurrent serious medical illness HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior irinotecan No prior topotecan Endocrine therapy Not specified Radiotherapy No prior radiotherapy to the chest or other areas containing 30% or more of marrow-bearing bone Surgery See Disease Characteristics Other No concurrent phenytoin, phenobarbital, or other antiepileptic prophylactic drugs No concurrent amifostine

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cisplatin|nan|
|Drug: irinotecan hydrochloride|nan|
|Procedure: conventional surgery|nan|
|Procedure: neoadjuvant therapy|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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limited stage small cell lung cancer