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references

[Bevacizumab references provided as separate document on diskette]
1. Kulke MH, Stuart K, Enzinger PC, et al. Phase II study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors. J Clin Oncol 2006;24:4016. 2. Strosberg JR, Fine RL, Choi J, et al. First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer 2011;117:268-75. 3. Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. The New England journal of medicine 2011;364:514-23. 4. Raymond E, Dahan L, Raoul JL, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. The New England journal of medicine 2011;364:501-13. 5. Ekeblad S, Sundin A, Janson ET, et al. Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors. Clin Cancer Res 2007;13:2986-91. 6. Strosberg JR, Fine RL, Choi J, et al. First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer 2010. 7. Kulke MH, Hornick JL, Frauenhoffer C, et al. O6-methylguanine DNA methyltransferase deficiency and response to temozolomide-based therapy in patients with neuroendocrine tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 2009;15:338-45. 8. Kulke M, Stuart K, Earle C, et al. A phase II study of temozolomide and bevacizumab in patients with advanced neuroendocrine tumors. J Clin Oncol 24: (June 20 suppl; abstr 4044) 2006. 9. Yao JC, Phan A, Hoff PM, et al. Targeting vascular endothelial growth factor in advanced carcinoid tumor: a random assignment phase II study of depot octreotide with bevacizumab and pegylated interferon alpha-2b. J Clin Oncol 2008;26:1316-23. 10. O'Reilly SM, Newlands ES, Glaser MG, et al. Temozolomide: a new oral cytotoxic chemotherapeutic agent with promising activity against primary brain tumours.  
Eur J Cancer 1993;29A:940-2. 11. Yung WK, Prados MD, Yaya-Tur R, et al. Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group. J Clin Oncol 1999;17:2762-71. 12. Tentori L, Graziani G, Gilberti S, Lacal PM, Bonmassar E, D'Atri S. Triazene compounds induce apoptosis in O6-alkylguanine-DNA alkyltransferase deficient leukemia cell lines. Leukemia 1995;9:1888-95. 13. Seiter K, Liu D, Loughran T, Siddiqui A, Baskind P, Ahmed T. Phase I study of temozolomide in relapsed/refractory acute leukemia. J Clin Oncol 2002;20:3249-53. 14. Brandwein JM, Schimmer AD, Schuh AC, et al. A Phase II Study of Temozolomide Therapy for Poor Risk Patients Age >= 60 Years with Acute Myeloid Leukemia (AML) - Low Levels of MGMT May Predict for Response. ASH Annual Meeting Abstracts 2005;106:1860-. 15. Maire F, Hammel P, Faivre S, et al. Temozolomide: a safe and effective treatment for malignant digestive endocrine tumors. Neuroendocrinology 2009;90:6772. 16. Isacoff W, Moss R, Pecora A, Fine R. Temozolomode/capecitabine therapy for metastatic neuroendocrine tumors of the pancreas. A retrospective review. J Clin Oncol 24: (June 20 suppl; abstr 14023) 2006. 17. Pecout S, Baudin E, Paoli A, et al. Efficacy and tolerance of chemotherapy with dacarbazine or temozolomide associated or not with 5-fluorouracil (5-FU) in endocrine carcinomas: A retrospective multicentric study from the Groupe des Tumeurs Endocrines (GTE). J Clin Oncol 29 (suppl; abstr e15523) 2009. 18. Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005;352:997-1003. 19. Qian XC, Brent TP. Methylation hot spots in the 5' flanking region denote silencing of the O6-methylguanine-DNA methyltransferase gene. Cancer Res 1997;57:3672-7. 20. Watts GS, Pieper RO, Costello JF, Peng YM, Dalton WS, Futscher BW. Methylation of discrete regions of the O6-methylguanine DNA methyltransferase (MGMT) CpG island is associated with heterochromatinization of the MGMT transcription start site and silencing of the gene. Mol Cell Biol 1997;17:5612-9. 21. Brandes AA, Tosoni A, Basso U, et al. Second-line chemotherapy with irinotecan plus carmustine in glioblastoma recurrent or progressive after first-line temozolomide chemotherapy: a phase II study of the Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO). J Clin Oncol 2004;22:4779-86.  
22. Tolcher AW, Gerson SL, Denis L, et al. Marked inactivation of O6-alkylguanineDNA alkyltransferase activity with protracted temozolomide schedules. Br J Cancer 2003;88:1004-11. 23. Schuller J, Cassidy J, Dumont E, et al. Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer chemotherapy and pharmacology 2000;45:291-7. 24. Guyennon A, Mihaila M, Palma J, Lombard-Bohas C, Chayvialle JA, Pilleul F. Perfusion characterization of liver metastases from endocrine tumors: Computed tomography perfusion. World J Radiol 2010;2:449-54.  
25. Ng CS, Charnsangavej C, Wei W, Yao JC. Perfusion CT findings in patients with metastatic carcinoid tumors undergoing bevacizumab and interferon therapy. AJR American journal of roentgenology 2011;196:569-76. 26. d'Assignies G, Couvelard A, Bahrami S, et al. Pancreatic endocrine tumors: tumor blood flow assessed with perfusion CT reflects angiogenesis and correlates with prognostic factors. Radiology 2009;250:407-16. 27. Park MS, Klotz E, Kim MJ, et al. Perfusion CT: noninvasive surrogate marker for stratification of pancreatic cancer response to concurrent chemo- and radiation therapy. Radiology 2009;250:110-7. 28. Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S. The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas 2010;39:707-12. 29. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47. 30. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9th ed. . Boston, MA: Little, Brown & Co; 1994. 31 Jeff A. Simerville, MD, William C. Maxted, MD, John J. Pahira, MD. Urinalysis: A
Comprehensive Review J. *Am Fam Physician.* 2005 Mar 15;71(6):1153-1162.  
32 Carroll MF1, Temte JL. Proteinuria in adults: a diagnostic approach. Am Fam Physician. 2000 Sep 15;62(6):1333-40. APPENDICES: Appendix A: NCI Common Toxicity Criteria, v4.0 (website provided)
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf Appendix B: FDA MedWatch 3500a Form (website provided)
http://www.fda.gov/Safety/MedWatch/HowToReport/DownloadForms/default.htm Appendix C: NYHA Guidelines (included) Appendix D: Genentech Safety Reporting Cover Sheet (included) ATTACHMENTS: Attachment 1: Informed Consent Form (separate attachment)
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appendix c nyha guidelines30

Class I (mild): no limitation is experienced in any activities; there are no symptoms from ordinary activities. Class II (mild): slight, mild limitation of activity; the patient is comfortable at rest or with mild exertion. Class III (moderate): marked limitation of any activity; the patient is comfortable only at rest. Class IV (severe): any physical activity brings on discomfort and symptoms occur at rest.
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appendix d safety reporting fax

AE / SAE FAX No: xxxxxxxxxx Alternate Fax No: xxxxxxxxxxx  
| Genentech Study Number Principal Investigator Site Name Reporter name Reporter Telephone # Reporter Fax #   | [INSERT investigational product name] / [INSERT                                                                         |
|-------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------|
| Initial Report Date                                                                                         | investigational product name] / [INSERT  investigational product name] [INSERT investigational product name] / [INSERT  |
| Follow-up Report Date                                                                                       | investigational product name] / [INSERT  investigational product name]                                                  |
| Subject Initials                                                                                            | [INSERT investigational product name] - [INSERT  investigational product name] - [INSERT  investigational product name] |
| (Enter a dash if patient has no  middle name)                                                               |                                                                                                                         |  
SAE or Safety Reporting questions, contact Genentech Safety: (xxxxxxxxxxx PLEASE PLACE MEDWATCH REPORT or SAFETY REPORT BEHIND THIS COVER SHEET