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 chemotherapy with radiation therapy may kill more tumor cells. PURPOSE: Phase I trial to study the effect on the body when combining irinotecan and cisplatin with radiation therapy in treating patients who have limited-stage small cell lung cancer that could not be completely removed during surgery.
Detailed description
OBJECTIVES: * Determine the maximum tolerated dose of irinotecan administered with cisplatin and thoracic radiotherapy (given at two different schedules) in patients with limited stage small cell lung cancer. * Determine the qualitative and quantitative toxicity and non-dose-limiting toxicity of these regimens in these patients. * Determine the reversibility of all toxic effects associated with these regimens in these patients. OUTLINE: This is a non-randomized, dose-escalation study of irinotecan. Patients are assigned to 1 of 2 radiotherapy (RT) treatment groups. * Radiotherapy: * Group I: Patients undergo thoracic RT twice daily, 5 days a week, for 3 weeks. * Group II: Patients undergo thoracic RT once daily, 5 days a week, for 7 weeks. * Concurrent chemotherapy: Patients receive irinotecan IV over 60-90 minutes on days 1 and 8 and cisplatin IV over 1 hour on day 1. Treatment repeats every 3 weeks for 1 course for group I and 2 courses for group II. * Post RT chemotherapy: Patients receive irinotecan and cisplatin as above for 3 courses for group I and 2 courses, beginning after RT is complete, for group II. Sequential cohorts of 6 patients per group receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 3 months for 1 year and then 6 months for 4 years. PROJECTED ACCRUAL: A total of 12-36 patients (6-18 per group) will be accrued for this study within 18 months.
Interventions
DRUGcisplatin
DRUGirinotecan hydrochloride
RADIATIONradiation therapy
Sponsors
National Cancer Institute (NCI)
Radiation Therapy Oncology Group
Study design
Allocation
NON_RANDOMIZED
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 lung cancer by one of two methods: * Fine needle aspiration biopsy * Two positive sputa * Must have limited disease as defined by all of the following: * Stage I-IIIB * Confined to 1 hemithorax * No T4 tumor based on malignant pleural or pericardial effusion * Patients with pleural effusion too small to tap under CT guidance and not evident on chest x-ray are allowed * No N3 disease based on contralateral hilar or contralateral supraclavicular involvement * Measurable or evaluable disease * Tumor must be able to be encompassed by specified radiotherapy fields without unacceptable risk of serious pulmonary compromise * No complete tumor resection * No pericardial effusion (regardless of cytology) PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Zubrod 0-1 Life expectancy * Not specified Hematopoietic * Absolute granulocyte count at least 1,500/mm\^3 * Platelet count at least 120,000/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 Cardiovascular * No myocardial infarction within the past 6 months * No symptomatic heart disease Pulmonary * Forced expiratory volume (FEV)\_1 at least 1.0 L/sec * No uncontrolled bronchospasms * No uncompensated chronic obstructive pulmonary disease Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No pre-existing peripheral neuropathy grade 2 or greater * No other malignancy within the past 2 years except curatively treated basal or squamous cell skin cancer or carcinoma in situ of the bladder or cervix * No other concurrent serious medical illness PRIOR CONCURRENT THERAPY: Biologic therapy * No prior biologic therapy Chemotherapy * No prior chemotherapy Endocrine therapy * Not specified Radiotherapy * No prior radiotherapy * No concurrent intensity-modulated radiotherapy Surgery * See Disease Characteristics Other * At least 7 days since prior enzyme-inducing anti-convulsant drugs (EIACDs) (e.g., phenytoin, carbamazepine, or phenobarbital) if used on a regular basis for more than 2 weeks * Less than 2 weeks of regular use of EIACDs does not require a 7-day wash-out period * At least 14 days since prior Hypericum perforatum (St. John's wort) * No concurrent EIACDs * No concurrent amifostine during chemoradiotherapy * Concurrent gabapentin or other non-EIACDs allowed
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose of irinotecan in combination with cisplatin and thoracic radiotherapy (45 Gy BID or 70 Gy daily) by toxicity assessment (Common Toxicity Criteria version 3.0) during acute and late toxicity | From the start of treatment until 90 days |
Secondary
| Measure | Time frame |
|---|---|
| Rate of non-dose limiting toxicity | From start of treatment to the end of follow-up |
Countries
United States
Outcome results
None listed