RATIONALE: Drugs used in chemotherapy such as irinotecan and cisplatin 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. Irinotecan and cisplatin may also make the tumor
cells more sensitive to radiation therapy. Combining chemotherapy with radiation therapy
before surgery may shrink the tumor so that it can be removed during surgery.
PURPOSE: This phase I trial is studying the side effects of neoadjuvant radiation therapy
given together with irinotecan and cisplatin followed by surgery in treating patients with
limited-stage small cell lung cancer.
- Determine the safety and feasibility of neoadjuvant chemoradiotherapy with irinotecan
and cisplatin followed by surgery in patients with limited stage small cell lung
- Determine the pathologic complete response rate of patients treated with this regimen.
- Correlate the level of vascular endothelial growth factor with treatment response and
disease outcome in patients treated with this regimen.
- Correlate genetic polymorphisms in cytochrome P450 1A1, glutathione S-transferase M1
and P1, myeloperoxidase, and NAD(p)H: quinone oxidoreductase with treatment response
and disease outcome in patients treated with this regimen.
OUTLINE: This is a pilot study.
- Induction chemotherapy: Patients receive cisplatin IV over 1 hour on day 1 and
irinotecan IV over 90 minutes on days 1 and 8.
- Chemoradiotherapy: Beginning on day 21, patients receive chemoradiotherapy comprising
radiotherapy once daily, 5 days a week for 4 weeks and then twice daily for 4 days.
Patients also receive cisplatin IV and irinotecan IV over 30-60 minutes once weekly
concurrently with radiotherapy. Treatment continues in the absence of disease
progression or unacceptable toxicity.
At the completion of chemoradiotherapy, patients are evaluated for surgery. Patients who are
candidates for surgery receive one additional course of cisplatin IV and irinotecan IV.
Patients who are not candidates for surgery receive radiotherapy twice daily for 4 days and
cisplatin IV and irinotecan IV as in chemoradiotherapy.
- Surgery: Approximately 2-4 weeks after the last dose of chemotherapy, patients undergo
Patients are followed every 4 months for 2 years and then every 6 months for 3 years.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
- Histologically or cytologically confirmed small cell lung cancer
- Limited stage disease (clinical stage I-IIIA) and meets the following criteria:
- Confined to 1 hemithorax
- No T4 disease based on malignant pleural effusion
- No N3 disease based on contralateral hilar or supraclavicular involvement
- Contralateral mediastinal (N3) nodes greater than 1.5 cm on CT scan must be
biopsied to rule out pathologic involvement
- Measurable or evaluable disease
- Tumor must be able to be encompassed by limited radiotherapy field without
significantly compromising pulmonary function
- No pleural effusion visible on chest x-ray (regardless of cytology)
- No prior complete tumor resection
- 18 and over
- Karnofsky 70-100%
- Not specified
- Absolute granulocyte count at least 1,800/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin no greater than 1.5 mg/dL
- No known Gilbert's disease
- Creatinine no greater than 1.5 mg/dL
- Calcium less than 12.0 mg/dL
- No myocardial infarction within the past 6 months
- No congestive heart failure
- No uncontrolled arrhythmias
- No active unstable angina
- Calculated postoperative FEV_1 at least 800 cc
- No chronic obstructive pulmonary disease with FEV_1 no greater than 1 L or
uncontrolled bronchospasm in the unaffected lung
- Not pregnant
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other malignancy within the past 2 years except curatively treated basal cell or
squamous cell skin cancer, carcinoma in situ of the cervix, or any other noninvasive
- No history of seizures
- No history of uncontrolled psychiatric illness that would preclude giving informed
consent or complying with study
- No active or uncontrolled infection
- No uncontrolled diabetes mellitus (random blood sugar at least 250 mg/dL)
- No other concurrent serious medical illness
- HIV negative
PRIOR CONCURRENT THERAPY:
- Not specified
- No prior irinotecan
- No prior topotecan
- Not specified
- No prior radiotherapy to the chest or other areas containing 30% or more of
- See Disease Characteristics
- No concurrent phenytoin, phenobarbital, or other antiepileptic prophylactic drugs
- No concurrent amifostine