Gefitinib With or Without Simvastatin in Non-Small Cell Lung Cancer (NSCLC)

Randomization

• Sex (female vs. male)
• ECOG PS (0/1 vs. 2/3)
• Number of prior regimen (one vs. two).

Gefitinib (250 mg per day) + Simvastatin (40 mg per day) PO or Gefitinib (250 mg per day) alone

until progression or unacceptable toxicity

Inclusion criteria

• Histologic or cytologic diagnosis of NSCLC
• Stage IV or selected stage IIIB (with positive pleural effusion or multiple ipsilateral lung nodules) according to the American Joint Committee on Cancer (AJCC).
• Previously treated with at least one platinum-based chemotherapy.
• Before study entry, a minimum of 21 days must have elapsed since any prior chemotherapy.
• Prior radiation therapy is allowed as long as the irradiated area is not the only source of measurable disease.
• No other forms of cancer therapy, such as radiation, immunotherapy for at least 2 weeks before the enrollment in study.
• Performance status of 0-3 on the ECOG criteria.
• At least one unidimensional measurable lesion meeting Response Evaluation Criteria in Solid Tumors (RECIST. 2000).- Estimated life expectancy of at least 8 weeks.
• Patient compliance that allow adequate follow-up.
• Adequate hematologic (ANC count ≥ 1,000/uL, platelet count ≥ 150,000/mm3), hepatic (bilirubin level≤1.5 mg/dL, AST/ALT ≤ 80 IU/L), and renal (creatinine concentration ≤ 1.5 mg/dL) function.
• Informed consent from patient or patient's relative.
• Males or females at least 18 years of age.
• If female: childbearing potential either terminated by surgery, radiation, or menopause, or attenuated by use of an approved contraceptive method (intrauterine device [IUD], birth control pills, or barrier device) during and for 3 months after trial. If male, use of an approved contraceptive method during the study and 3 months afterwards. Females with childbearing potential must have a urine negative hCG test within 7 days prior to the study enrollment.
• No concomitant prescriptions including cyclosporin A, valproic acid, phenobarbital, phenytoin, ketoconazole.
• Patients with brain metastasis are allowed unless there were clinically significant neurological symptoms or signs

Exclusion criteria

• Presence of small-cell lung cancer alone or with NSCLC- Unresolved chronic toxic effects from previous anticancer therapy
• Known severe hypersensitivity to gefitinib or any of the tablet excipients
• Inability to swallow tablets
• Other coexisting malignant disease (apart from basal-cell carcinoma)
• More than three previous chemotherapy regimens for NSCLC
• Previous treatment with an experimental agent of which the main mechanism of action is inhibition of epidermal growth factor receptor or its associated tyrosine kinase
• Concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St John's wort; severe or uncontrolled systemic disease; clinically active interstitial lung disease (except uncomplicated lymphangitic carcinomatosis) pregnancy; and breastfeeding.
• MI within preceding 6 months or symptomatic heart disease, including unstable angina, congestive heart failure or uncontrolled arrhythmia
• Serious concomitant infection including post obstructive pneumonia
• Major surgery other than biopsy within the past two weeks.
• Pregnant or breast-feeding.