Iressa/Docetaxel in Non-Small-Cell Lung Cancer

A Phase II Study of ZD1839 (Iressa), Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor, in Combination With Docetaxel in Patients With Recurrent or Metastatic Advanced Non-Small Cell Lung Cancer

Patients will receive 250 mg Iressa by mouth daily each day while on this study. Patients will also receive docetaxel 30 mg/m2 by by vein (IV) on day 1 weekly for the first 3 weeks of each course of therapy. A course of therapy is 4 weeks. Patients will not receive docetaxel during week 4. A maximum of 8 full cycles of docetaxel plus Iressa are planned. Patients may continue on daily Iressa until progressive disease and/or unacceptable toxicity.

Inclusion Criteria:

• Pathologically confirmed non-small cell lung cancer.
• Measurable, evaluable disease outside of a radiation port.
• ECOG performance status 0-2.
• Adequate hematologic function as defined by an absolute neutrophil count >= 1,500/mm3, a platelet count >= 100,000/mm3, a WBC >= 3,000/ mm3, and a hemoglobin level of >= 9 g/dl.
• One prior chemotherapy regimen. This may include chemoradiation treatment.
• Disease progression or recurrence within 6 months of last dose of chemotherapy in first chemotherapy regimen.
• At least a 2-week recovery from prior therapy toxicity.
• Signed informed consent.
• Prior CNS involvement by tumor are eligible if previously treated and clinically stable for two weeks after completion of treatment.

Exclusion Criteria:

• Prior Iressa or other EGFR inhibiting agents
• Prior docetaxel therapy
• Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ.
• Any unresolved chronic toxicity greater than CTC grade 2 from previous anticancer therapy.
• Incomplete healing from previous oncologic or other major surgery.
• Concomitant use of phenytoin, carbamazepine, barbiturates, rifampicin, St John's Wort, anti-coagulants.
• Absolute neutrophil counts less than 1500 x 109/liter (L) or platelets less than 100,000x 109/liter (L).
• Serum bilirubin greater than 1.25 times the upper limit of reference range (ULRR).
• In the opinion of the investigator, any evidence of severe or uncontrolled systemic disease, (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease).
• A serum creatinine >= 1.5 mg/dl and calculated creatinine clearance <= 60 cc/minute.
• Alanine amino transferase (ALT) or aspartate amino transferase (AST) greater than 2.5 times the ULRR if no demonstrable liver metastases or greater than 5 times the ULRR in the presence of liver metastases.
• Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the trial.
• Pregnancy or breast feeding
• The patient has uncontrolled seizure disorder, active neurological disease, or Grade >= 2 neuropathy
• The patient has received any investigational agent(s) within 30 days of study entry.
• The patient has signs and symptoms of keratoconjunctivitis sicca or incompletely treated eye infection.