Given the activity of single-agent Topotecan in NSCLC, there is both scientific rationale and a medical interest in studying this agent in combination with radiation. In addition, Topotecan administered on a weekly basis offers advantages over the daily x 5 regimen, i.e., the convenience of administration and fewer visits to the clinic.

This is a study of chemoradiation for patient with inoperable non small cell lung cancer with poor pulmonary function. These patients have usually very limited treatment options because of the compromised lung function. Chemoradiation is usually superior to radiation alone, but has not been extensively tested in this patient population. Topotecan is a drug approved for lung cancer that has synergistic activity with radiation. The study will determine what is the safest dose of topotecan to use with radiation in this patient population

Inclusion Criteria:

• Patients with histologically proven non-small cell lung cancer Stage I to IIIA.
• Inoperable lung cancer because of poor respiratory lung function, or other medical reasons, as determined by the thoracic surgeon.
• PS < 2
• Age > 18 years
• Life expectancy of > 12 weeks
• Normal hematologic, liver, and renal function
• No metastatic disease as determined by CT-PET scanning and bone scan.
• No brain metastasis by MRI
• No contraindication to radiotherapy

Exclusion Criteria:

• Patients with uncontrolled CNS metastases.
• Active systemic infection.
• Serious, uncontrolled intercurrent medical or psychiatric illness.
• Secondary active primary malignancy.
• Inability to comply with requirements of the study.
• Any metastases outside of the mediastinum
• Histologically positive pleural or pericardial effusion
• Any chemotherapy within five years prior to enrollment on this protocol
• Prior radiotherapy administered to the chest
• Women who are pregnant or lactating
• FEV1 < 1 liter/minute