Phase I/II Study of Inhaled Doxorubicin Plus IV Docetaxel and Cisplatin in Patients With Locally Advanced or Metastatic Unresectable Non Small Cell Lung Cancer

Inclusion Criteria:

- Histologic or cytologic proof of locally advanced or metastatic unresectable NSCLC,
Patients with the pneumonic form of BAC, or cavitary lesions > 3.5 cm or with
cavitary lesions of any size with air/fluid levels are not eligible.

- No prior chemotherapy or biologic therapy for lung cancer

- Measurable or evaluable pulmonary disease required

- Age > 18 years

- ECOG performance status of 0-1

- Adequate bone marrow, hepatic, and renal function

- Total bilirubin < ULN

- SGOT and/or SGPT may be up to 2.5 x ULN if alkaline phosphatase is ≤ ULN, or alkaline
phosphatase may be up to 4 x ULN if SGOT and SGPT are both ≤ ULN

- Creatinine <1.5 mg/dL or creatinine clearance > 60 mL/min/1.7 m2 BSA

- Patients must have the following pulmonary function test values:

- DLCO > 50% predicted. (DLCO must be adjusted for the patient’s hemoglobin)

- FVC> 50% of predicted

- FEV1 >50% of predicted

- Resting oxygen saturation > 90%

- Exercise oxygen saturation > 85%

- Prior surgery is permitted provided full recovery has occurred

- Patients may not have received prior radiotherapy to the lungs. Patients with only
chest wall or breast irradiation are eligible provided there is no radiographic
evidence of pulmonary damage attributed to radiation therapy. Patients who have
undergone Radioactive Iodine (RAI) therapy are also eligible.

- Patients must sign an informed consent indicating that they are aware of the
investigational nature of this study.

Exclusion Criteria:

- Women must not be pregnant or breast-feeding during this study. Men and women with
reproductive potential must use an effective contraceptive method while on this study
and agree to use an effective method for three months after completing chemotherapy.

- Patients with large obstructive pulmonary lesions that may cause blockage of delivery
of aerosolized drug to the affected lung, in the judgment of the treating physician.
A ventilation scan is recommended if the status is unclear.

- Patients with other active malignancies. Patients with a history of prior malignancy
other than NSCLC must not have received chemotherapy within the past 5 years and may
not have had prior therapy with mitomycin (> 25 mg/m2), bleomycin or nitrosoureas (>
200 mg/m2). The patient may not have had any indication of pulmonary toxicity from
the chemotherapy.

- Serious active infections which are not controlled such that the patient continues to
manifest symptoms despite treatment

- Patients with progressive extra-pulmonary metastases who are unlikely to benefit from
systemic or inhaled chemotherapy, e.g., extensive liver metastases, untreated brain
metastases or treated brain metastases which are not clinically stable. If patients
have received radiation treatment for brain metastases, at least 3 weeks must have
elapsed since the last treatment and the patient must have recovered from all
toxicity, not be receiving corticosteroids and have stable neurologic function off
corticosteroids.

- Patients with known hypersensitivity to platinum compounds or taxanes or other drugs
formulated with polysorbate 80

- asthma

- uncontrolled diabetes mellitus

- Patients who have undergone lung transplantation

- unstable angina, congestive heart failure, or symptomatic arrhythmias or any other
serious illness or medical condition that in the judgment of the investigator
compromises the patient’s safety

- clinically significant neuropathy (≥ Grade 1) by history or physical examination

- Patients using other investigational drugs