Patient description: A 34 year old man comes to the clinic complaining of dizziness and severe diarrhea since yesterday. He has returned from an international trip few days ago and was living in a camp in Sudan for a month. He developed abdominal pain followed by bloating and nausea as well as loose bowel movements. Soon he was having profuse watery diarrhea without odor. The stool is watery and white but the patient has no fever. Blood pressure is 95/62 lying down and drops to 75/40 standing. The skin turgor has reduced. HR is 110 and he looks ill with dry mucosa. V. cholerae was seen in dark-field microscopy of a fresh stool specimen. The lab study is as bellow: Sodium 137 meq/L Potassium 2 meq/L Chloride 94meq/L CO2 15 meq/L Fecal leukocytes None seen Fecal occult blood Negative

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Pancreatic Neuroendocrine Cancer Histologically or cytologically proven diagnosis of pancreatic neuroendocrine tumors (pNET) with Ki67 assessment of < or = 20% (well and moderately differentiated) with evidence of unresectable disease or metastatic disease. Locally advanced disease must not be amendable to resection or radiation therapy with curative intent. 2. Overexpression of Cdk4 and/or phospho-Rb1 and/or cyclin D1 in tumor tissue sample from tumor biopsy or prior primary tumor resection (Molecular study will be conducted at CNIO and logistic is described later). Therefore availability of paraffin-embedding tumor tissue sample is needed. 3. Documented progression of the disease by CT scan, MRI, or Octreoscan within 12 months prior to baseline. 4. Previous treatments with chemotherapy, antiangiogenics, or interferon are permitted providing that toxicity has resolved to < grade 1 at study entry and that last treatment was at least 4 weeks prior to baseline assessment. Patients may be treated with somatostatin analogues during the trial. Concomitant interferon treatment is not permitted. 5. Measurable disease as per Measurable lesions that have been previously radiated will not be considered target lesions unless increase in size has been observed following completion of radiation therapy. 6. Able to swallow oral compound 7. Male or female, 18 years of age or older. 8. ECOG performance status less than 2. 9. Life expectancy greater than 12 weeks. 10. The definitions of minimum adequacy for organ function required prior to study entry are as follows. In addition, safety precautions provided in the product labeling for the anticipated control arm chemotherapy must be observed Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) 2.5 x upper limit of normal (ULN), or AST and ALT 5 x ULN if liver function abnormalities are due to underlying malignancy Total serum bilirubin 1.5 x ULN Serum albumin 3.0 g/dL Absolute neutrophil count (ANC) 1500/L Platelets 100,000/L Hemoglobin 9.0 g/dL Creatinin clearance < 40 mL/min 11. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment. 12. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures  Prior chemotherapy regimen or biological treatment for locally advanced or metastatic transitional cell carcinoma of the urinary tract. 2. Prior treatment on Cdk4 inhibitor under clinical trial. 3. Creatinine clearance < 40 ml/min using Cockroft and Gault formula. 4. Major surgery, radiation therapy, or systemic therapy within 3 weeks of study randomization except palliative radiotherapy to non-target metastatic lesions. 5. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue. 6. Immunosuppressive drugs such as cyclosporine, tacrolimus, azathioprine, or long-term oral glucocorticoids taken concurrently or within last 3 months prior to randomization 7. Prior radiation therapy to >25% of the bone marrow. 8. Current treatment on another clinical trial. 9. Uncontrolled brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease. Patients should have completed surgery or radiation therapy for existing brain metastases, should not have documented increase in size over the previous 3 months prior to first dose of treatment on study and should be asymptomatic. 10. Diagnosis of any second malignancy within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix. 11. Any of the following within the 12 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack, or pulmonary embolus. 12. Ongoing cardiac dysrhythmias of NCI CTCAE grade 2, atrial XML File Identifier: 3xAP+CVEwV9UnEoC7xvloFQA/XQ=Page 20/34 fibrillation of any grade, or QTc interval >450 msec for males or >470msec for females. 13. Hypertension that cannot be controlled by medications (>150/100mmHg despite optimal medical therapy) 14. Current treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed). 15. Known human immunodeficiency virus infection. 16. Pregnancy or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to randomization. 17. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study