Cisplatin, Etoposide, and Radiation Therapy 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 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. Combining more than one chemotherapy drug with radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving cisplatin and etoposide together with radiation therapy works in treating patients with limited-stage small cell lung cancer.

Detailed Description
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OBJECTIVES: Determine the response rate of patients with limited stage small cell lung cancer treated with cisplatin and etoposide combined with accelerated high-dose thoracic radiotherapy. Determine the progression-free and overall survival in patients treated with this regimen. Determine the qualitative and quantitative toxicity and reversibility of toxicity of this regimen in these patients. OUTLINE: Patients undergo radiotherapy once daily 5 days a week for approximately 3 weeks and then twice daily 5 days a week for approximately 2 weeks (a total of 9 treatment days during the final 2-week treatment period). Beginning on the first day of radiotherapy, patients receive cisplatin IV over 2 hours and etoposide IV over 1 hour on day 1 and oral etoposide once daily on days 2 and 3. Chemotherapy repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 71 patients will be accrued for this study within 18 months.

Official Title
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A Phase II Study Of Accelerated High Dose Thoracic Irradiation With Concurrent Chemotherapy For Patients With Limited Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Cisplatin
* Drug: Etoposide
* Radiation: Radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed small cell carcinoma of the lung by fine needle aspiration biopsy or two positive sputa Must have limited disease Stage I, II, IIIA, or IIIB Confined to 1 hemithorax, but excluding the following: T4 tumor based on malignant pleural effusion N3 disease based on contralateral hilar or contralateral supraclavicular involvement No pericardial or pleural effusions on chest x-ray (regardless of cytology) Measurable or evaluable disease Tumor must be able to be encompassed by limited radiotherapy fields without significantly compromising pulmonary function No prior complete tumor resection PATIENT CHARACTERISTICS: Age 18 to 100 Performance status Zubrod 0-1 Life expectancy Not specified Hematopoietic Absolute granulocyte count at least 1,500/mm^3 Platelet count at least 150,000/mm^3 Hepatic Bilirubin no greater than 1.5 mg/dL Renal Creatinine no greater than 1.5 mg/dL Cardiovascular No myocardial infarction within the past 6 months No symptomatic heart disease Pulmonary No chronic obstructive pulmonary disease with Forced Expiratory Volume (FEV)-1 no greater than 0.8 liter No uncontrolled bronchospasm in the unaffected lung Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Available for follow-up No other malignancy within the past 2 years except curatively treated basal cell or squamous cell skin cancer or non-invasive in situ malignancies No other concurrent serious medical illness No uncontrolled psychiatric illness No chronic alcohol or drug abuse PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy Endocrine therapy Not specified Radiotherapy No prior radiotherapy to the chest or other area containing a large amount of bone marrow (e.g., more than 75% of pelvic bone) Surgery See Disease Characteristics

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radiation Therapy + Chemotherapy<br>Accelerated high dose thoracic radiation therapy (RT) with concurrent cisplatin/etoposide chemotherapy, followed by 2 cycles of adjuvant cisplatin/etoposide chemotherapy | Drug: Cisplatin<br>* 60 mg/m2 given intravenously. During RT, give on day 1 and day 22. After completion of RT, on days 43 and 64.<br>Drug: Etoposide<br>* 120 mg/m2 given intravenously. During RT, give on days 1-3, then days 22-24. After completion of RT, on days 43-45 and days 64-66.<br>Radiation: Radiation therapy<br>* Large field 28.8 Gy: 1.8 Gy per fraction, 5 days per week for 16 fractions. On days 23-26, BID: use anteroposterior and posteroanterior (AP/PA) fields in a.m. at 1.8 Gy per fraction; boost with 2nd treatment in p.m. at 1.8 Gy per fraction. Then off-cord boost, 1.8 Gy, BID, x last 5 days for a total dose of 61.2 Gy in 5 wks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival at 2 Years | Survival time is defined as time from study registration to the date of death from any cause and survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. | From registration to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) and Progression-free Survival (PFS) at 1 Year | An event for overall survival is death due to any cause. Overall survival time is defined as time from study registration to the date of death from any cause. An event for progression-free survival is the first of the following: local progression, regional progression, distant metastases, or death due to any cause. Progression-free survival time is defined as time from study registration to the date of first failure. For both outcome measures, patients last known to be alive without failure are censored at the date of last contact. Survival rates are estimated by the Kaplan-Meier method. | From registration to one year. | 
| Median Overall Survival Time and Progression-free Survival Time | An event for overall survival is death due to any cause. Overall survival time is defined as time from study registration to the date of death from any cause. An event for progression-free survival is the first of the following: local progression, regional progression, distant metastases, or death due to any cause. Progression-free survival time is defined as time from study registration to the date of first failure. For both outcome measures, patients last known to be alive without failure are censored at the date of last contact. Survival rates are estimated by the Kaplan-Meier method. | From registration to 2 years | 
| Number of Patients With Acute Treatment-related Grade 3 or 4 Esophagitis | Highest grade treatment-related toxicity per subject was counted. Toxicities were graded using Common Toxicity Criteria (CTC) v 2.0. Grade refers to the severity of the toxicity. Both criteria assign Grades 1 through 5 with unique clinical descriptions of severity for a given toxicity based on this general guideline: Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening or disabling, Grade 5= Death related to toxicity. | From start of radiation therapy until 90 days following the start of radiation therapy | 
| Frequency of Treatment-related Fatalities at 2 Years | A treatment-related fatality was any death judged to be related to protocol treatment. | From the start of treatment to 2 years | 
| Tumor Response | Response will be recorded as the best response observed two months after the completion of chemoradiation therapy. Tumor response as defined by Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): Disappearance of all target lesions as measured by MRI, CT, or physical examination (this is the order of preference for measurement). Partial Response (PR): >= 30% decrease in the sum of the longest diameter (LD) of target lesions (order of preference for measurement is MRI, CT, physical examination). Progressive Disease (PD): >= 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions (order of preference for measurement is MRI, CT, physical examination). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. | From the start of treatment to 2 months following the completion of chemotherapy | 

 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