| Exclusion Criteria: | 1) Prior treatment with a MEK inhibitor
2) Previous enrollment or assignment to treatment in the present study
3) Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site)
4) Having received an investigational drug within the 30 days prior to entry or patients who have not recovered from side effects of an investigational study drug
5) Recent major surgery within 4 weeks prior to consent (excluding the placement of vascular access) which would prevent administration of standard chemotherapy
6) Radiotherapy or standard chemotherapy within 21 days prior to entry into the study (not including palliative radiotherapy at focal sites)
7) Brain metastases or spinal cord compression unless treated and stable (for at least 1 month) off steroids
8) Evidence of active infection or active bleeding diatheses
9) Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
10) Patients with factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) or QTc interval of > 450ms for males or > 470ms for females on screening
11) Evidence of severe or uncontrolled systemic disease (e.g., severe hepatic impairment, severe renal impairment uncontrolled diabetes, acute uncontrolled infection) or current unstable or uncompensated respiratory or cardiac conditions or peripheral vascular disease including diabetic vasculopathy, or renal transplant
12) Patients with documented cases of human immunodeficiency virus (HIV) or active hepatitis B or C infection
13) Laboratory values as listed below: Absolute Neutrophil Count (ANC) < 1500 per mm3, Platelets < 100,000 per mm3 - Hemoglobin (Hgb) < 9.0 g/dL - Serum bilirubin >/= 1.5x Upper Limit of Normal (ULN) (known Gilbert's disease is allowed) - Aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) >/= 2.5 x ULN or 5 x ULN if liver metastases - Patients with proteinuria > 2gr/24hr urine collection are excluded.
14) Clinical judgment by the Investigator that the patient should not participate in the study
15) Known hypersensitivity to the standard chemotherapy proposed for the patient.
16) Cardiac conditions as follows: Uncontrolled hypertension (BP150/95 despite optimal therapy) - Heart failure NYHA Class II or above - Prior or current cardiomyopathy - Baseline LVEF </= 50% - Atrial fibrillation with heart rate >100bpm - Unstable ischemic heart disease (MI within last 6 months, or angina requiring use of nitrates more than once weekly)
17) Use of strong CYP1A2 or 3A4 inducers and/or inhibitors (for example, but not limited to, ketoconazole, rifampacin, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO), voriconazole, grapefruit or grapefruit juice, ifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital and St. John's Wort)
18) Current smokers or use of any tobacco (erlotinib arm only) |