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

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.

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.

Eligibility 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