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 radiation therapy with chemotherapy may kill more tumor cells.
PURPOSE: Phase I/II trial to compare the effectiveness of gemcitabine with radiation therapy
alone or following two-drug combination chemotherapy in treating patients with stage III
non-small cell lung cancer.
- Determine the maximum tolerated dose of twice-weekly gemcitabine when delivered
concurrently with thoracic radiotherapy alone or following 2 cycles of induction
chemotherapy in patients with Stage IIIA or IIIB non-small cell lung cancer.
- Assess the toxicity of concurrent thoracic radiation and gemcitabine in these patients.
- Determine the effectiveness of concurrent radiation and gemcitabine by determining the
complete response rate, partial response rate, time to recurrence, pattern of
recurrence, and overall survival in a cohort of these patients.
OUTLINE: This is an alternating two arm, dose escalation, multicenter study.
Arm I: Patients receive twice-weekly gemcitabine as a 30 minute infusion. Concurrent
radiation therapy is administered 5 days a week for 6 weeks.
Arm II: Patients receive 2 cycles of induction chemotherapy consisting of gemcitabine as a
30 minute infusion on day 1 and 8 and cisplatin IV over 1 hour on day 1. Each cycle is 21
days. Patients then receive gemcitabine and radiation therapy as in arm I.
Cohorts of 3 patients are enrolled into each treatment arm at each dose level of
gemcitabine. Toxicity for each arm is assessed independently. Once dose limiting toxicity
(DLT) is observed at any dose level, 3 more patients are enrolled at the same dose level.
The maximum tolerated dose (MTD) is defined as the dose at which no more than 1 of 6
patients experiences grade 4 toxicity, or no more than 4 of 6 patients experience grade 3 or
worse toxicity (DLT). After the MTD is determined for each treatment arm, additional
patients are treated at that dose level for the phase II portion of the study.
Patients are followed every 3 months for 2 years, then every 4 months for the next 2 years,
and then every 6 months thereafter.
PROJECTED ACCRUAL: There will be approximately 24-48 patients accrued into this study within
- Histologically confirmed stage IIIA or IIIB non-small cell lung cancer that is
unicentric and inoperable, including the following cellular types:
- Squamous cell carcinoma
- Bronchoalveolar carcinoma
- Large cell anaplastic carcinoma
- Non-small cell lung cancer not otherwise specified
- Tumors may be multifocal if all of disease is believed to be result of direct spread
- Disease must be fully accessible by radiotherapy ports for the entire prescribed dose
- No supraclavicular nodes or diffuse pleural involvement
- No contralateral hilar disease or an exudative, bloody, or cytologically malignant
- Measurable disease required for phase II of this study
- Any age
- ECOG 0-2
- At least 1 year
- Granulocyte count at least 1,500/mm3
- Platelet count at least 100,000/mm3
- Hemoglobin greater than 10 g/dL
- Bilirubin no greater than 2.0 mg/dL
- BUN no greater than 1.5 times normal
- Creatinine no greater than 1.5 times normal
- FEV1 no greater than 1 liter except if tumor has negatively impacted
- pulmonary function
- No other serious medical or psychiatric illness
- No prior lung cancer except if free of disease for more than 3 years
- No other prior malignancy except nonmelanoma skin cancer or if free of
- disease for more than 1 year
- Not pregnant or nursing
- Negative pregnancy test
PRIOR CONCURRENT THERAPY:
- Not specified
- No prior chemotherapy
- Not specified
- No prior thoracic radiotherapy
- Concurrent radiotherapy to other anatomic sites allowed
- Not specified