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