Phase II Study Alimta and Gemzar + Avastin as First Line Chemotherapy for Elderly Patients With Stage IIIB/IV NSCLC

Inclusion Criteria

• Patient provides voluntary written informed consent before performance of any study-related procedure not part of normal medical care.
• Patient ≥ 65 years of age with ECOG of 0 to 1
• Patient must have histologically/cytologically confirmed Stage IIIB/IV NSCLC.
• Patient has measurable disease defined as at least 1 lesion that can be accurately measured in at least 1 dimension (by CT or MRI) & used to assess response as defined by RECIST criteria. Tumors within a previously irradiated field will be designated nontarget lesions.
• Patient has not received radiotherapy within 2 weeks(4 weeks required for brain metastases radiotherapy)of initial chemotherapy dosing for this study, and all acute toxicities due to prior radiotherapy have resolved prior to initial chemotherapy dosing.
• Patient has a negative serum pregnancy test or has undergone hysterectomy at time of enrollment.
• Greater than 12 weeks life expectancy.
• Patient has recovered from any recent surgery for at least 30 days & is free of active infection requiring antibiotics.
• Patient must be willing/able to discontinue use of NSAIDS prior to study drug dosing.
• Patient must be able to take folic acid, Vitamin B12, & dexamethasone per protocol.
• Patient must exhibit no greater than Grade 1 peripheral neuropathy.

Exclusion Criteria

• Prior systemic or other concurrent chemo for metastatic NSCLC(Prior Tarceva is not allowed).Prior adjuvant chemo acceptable as long as > 12 months since completion and no prior pemetrexed, gemcitabine or bevacizumab.
• Lung carcinoma of squamous cell histology(mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient is ineligible; sputum cytology alone is acceptable.Patients with extrathoracic-only squamous cell NSCLC are eligible.Patients with only peripheral lung lesions (of any NSCLC histology) will also be eligible(a peripheral lesion is defined as a lesion in which the epicenter of the tumor is ≤ 2 cm from the costal or diaphragmatic pleura in a three-dimensional orientation based on each lobe of the lung and is > 2 cm from the trachea, main, and lobar bronchi).
• Hemoptysis within 1 month prior to study enrollment
• Ongoing treatment with full-dose warfarin or its equivalent i.e., unfractionated and/or low molecular weight heparin.(Low dose warfarin 1 mg given for prophylaxis is allowed).
• Hypersensitivity to any component of Alimta, gemcitabine &/or bevacizumab, &/or cannot tolerate folic acid, corticosteroids or Vitamin B12 supplements.
• Currently/have recently taken long-acting NSAID (Ibuprofen ≤ 400 mg QID acceptable) or aspirin (>325mg/day) within 5 days of initial pemetrexed administration.
• Clinically significant pericardial/pleural effusion or ascites unless able to be drained before study entry.
• Presence of third space fluid which cannot be controlled by drainage.
• Core biopsy/other minor surgical procedure(excluding placement of a vascular access device)within 7 days prior to study enrollment.
• Active infection or fever ≥ 38.5°C within 3 days of first scheduled day of protocol treatment.
• Serious, non-healing wound, ulcer, or untreated bone fracture.
• NYHA Grade II or greater CHF
• Inadequately controlled hypertension (defined as systolic blood pressure > 150 &/or diastolic blood pressure > 100mmHg on antihypertensive meds)
• Any prior history of hypertensive crisis or hypertensive encephalopathy.
• History of MI, CVA, TIA, or unstable angina within 6 months of study enrollment.
• Significant vascular disease (aortic aneurysm, aortic dissection or recent peripheral arterial thrombosis.)
• Symptomatic peripheral vascular disease
• Known bleeding diathesis or coagulopathy
• Presence of CNS(central nervous system) except for treated brain metastases. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by cl