Neoadjuvant Chemoradiotherapy (Gemcitabine/Cisplatin and Taxotere) With or Without Co-Administration of ZD 1839 (Iressa) for Stage IIIA (N2) and Selective Stage IIIB Non-Small Cell Lung Cancer: Phase I-II Study
OBJECTIVES: Phase I:
- Determine the tolerability and toxicity of gefitinib in combination with chest
radiotherapy in patients with stage IIIA or stage IIIB non-small cell lung cancer.
- Compare the pathologic response (complete response and rate of downstaging) in patients
treated with neoadjuvant chemoradiotherapy with vs without gefitinib.
- Compare the feasibility and toxicity profile of these regimens in these patients.
- Compare the resection rates, time to progression, and overall survival of patients
treated with these regimens.
- Correlate the percent decline in the fludeoxyglucose F 18 standardized uptake value as
measured by position emission tomography with pathologic response at resection, time to
progression, and overall survival in patients treated with these regimens.
- Phase I: This is an open-label, nonrandomized study.
- Induction: Patients receive cisplatin IV over 60 minutes on day 1 and gemcitabine
IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks for a total of
2 courses in the absence of disease progression or unacceptable toxicity.
- Consolidation: Within 3-4 weeks after the completion of induction therapy,
patients undergo radiotherapy once daily 5 days a week for 5 weeks and receive
oral gefitinib once daily concurrently.
A cohort of 3-6 patients receives consolidation chemoradiotherapy. If 2 of 6 patients
experience dose-limiting toxicity, gefitinib is deleted from consolidation therapy in phase
II arm II.
- Surgery: Patients without disease progression after consolidation therapy undergo
thoracotomy within 3-5 weeks after consolidation.
- Maintenance: Beginning 2-4 weeks after surgery, patients receive oral gefitinib once
daily for 6 months in the absence of disease progression.
- Phase II: This is a randomized study. Patients are randomized to 1 of 2 treatment
- Arm I: Patients receive induction and consolidation therapy (with the exception of
gefitinib) as in phase I. Patients also receive docetaxel IV over 60 minutes
concurrently with radiotherapy during consolidation. Patients undergo surgery as in
- Arm II: Patients receive therapy (including gefitinib) as in phase I. Patients also
receive docetaxel IV over 60 minutes concurrently with radiotherapy during
Patients are followed every 6-8 weeks for the first 12 months and then every 4-6 months
PROJECTED ACCRUAL: A total of 43-80 patients (3-6 patients for phase I and 40-74 patients
[20-37 per treatment arm] for phase II) will be accrued for this study.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Determine the tolerability and toxicity of gefitinib in combination with chest radiotherapy in patients with stage IIIA or stage IIIB non-small cell lung cancer.
Francisco Robert, MD, FACP
University of Alabama at Birmingham
United States: Federal Government
|University of Alabama at Birmingham Comprehensive Cancer Center||Birmingham, Alabama 35294-3300|