Chemotherapy Combined With Radiation Therapy in Treating Patients With Limited-Stage Small Cell Lung Cancer

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.

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