Lung Cancer
Conditions
Keywords
limited stage small cell lung cancer
Brief summary
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
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.
Interventions
DRUGCisplatin
60 mg/m2 given intravenously. During RT, give on day 1 and day 22. After completion of RT, on days 43 and 64.
DRUGEtoposide
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.
RADIATIONRadiation therapy
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.
Sponsors
National Cancer Institute (NCI)
Radiation Therapy Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival at 2 Years | From registration to 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) and Progression-free Survival (PFS) at 1 Year | From registration to one 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. |
| Median Overall Survival Time and Progression-free Survival Time | From registration to 2 years | 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. |
| Number of Patients With Acute Treatment-related Grade 3 or 4 Esophagitis | From start of radiation therapy until 90 days following the start of radiation therapy | 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. |
| Frequency of Treatment-related Fatalities at 2 Years | From the start of treatment to 2 years | A treatment-related fatality was any death judged to be related to protocol treatment. |
| Tumor Response | From the start of treatment to 2 months following the completion of chemotherapy | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Radiation Therapy + Chemotherapy Accelerated high dose thoracic RT with concurrent cisplatin/etoposide chemotherapy, followed by 2 cycles of adjuvant cisplatin/etoposide chemotherapy | 71 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | No protocol treatment received | 1 |
Baseline characteristics
| Characteristic | Radiation Therapy + Chemotherapy |
|---|---|
| Age, Continuous | 71 years |
| Sex: Female, Male Female | 34 Participants |
| Sex: Female, Male Male | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 71 / 71 |
| serious Total, serious adverse events | 67 / 71 |
Outcome results
Primary
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.
Time frame: From registration to 2 years
Population: All eligible patients who started study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radiation Therapy + Chemotherapy | Overall Survival at 2 Years | 36.60 percentage of participants |
Comparison: This study was designed to detect an improvement in the 2-year overall survival rate from 47% to 60%. Using a one-group chi-square test with a one-sided significance level of 0.10, a sample of 67 patients was deemed sufficient to detect the difference between the null hypothesis (H0: P .47) and the alternative hypothesis (HA: P .60) with 80% power.
Secondary
Frequency of Treatment-related Fatalities at 2 Years
A treatment-related fatality was any death judged to be related to protocol treatment.
Time frame: From the start of treatment to 2 years
Population: Eligible patients who started study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiation Therapy + Chemotherapy | Frequency of Treatment-related Fatalities at 2 Years | 2 Participants |
Secondary
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.
Time frame: From registration to 2 years
Population: All eligible patients who started study treatment
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Radiation Therapy + Chemotherapy | Median Overall Survival Time and Progression-free Survival Time | Overall Survival | 19.0 months |
| Radiation Therapy + Chemotherapy | Median Overall Survival Time and Progression-free Survival Time | Progression-free Survival | 9.9 months |
Secondary
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.
Time frame: From start of radiation therapy until 90 days following the start of radiation therapy
Population: Eligible patients who started study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiation Therapy + Chemotherapy | Number of Patients With Acute Treatment-related Grade 3 or 4 Esophagitis | 13 Participants |
Secondary
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.
Time frame: From registration to one year.
Population: Eligible patients who started study treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radiation Therapy + Chemotherapy | Overall Survival (OS) and Progression-free Survival (PFS) at 1 Year | Overall Survival | 77.5 percentage of participants |
| Radiation Therapy + Chemotherapy | Overall Survival (OS) and Progression-free Survival (PFS) at 1 Year | Progression-free Survival | 42.3 percentage of participants |
Secondary
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.
Time frame: From the start of treatment to 2 months following the completion of chemotherapy
Population: Eligible patients who started study treatment and were observed for at least 2 months post-treatment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Radiation Therapy + Chemotherapy | Tumor Response | Partial Response | 28 Participants |
| Radiation Therapy + Chemotherapy | Tumor Response | Progressive Disease | 4 Participants |
| Radiation Therapy + Chemotherapy | Tumor Response | Complete Response | 29 Participants |
| Radiation Therapy + Chemotherapy | Tumor Response | Stable Disease | 7 Participants |