Cancer Research: The Past and Future and the Hoosier Oncology Group

1. Cancer Research:The Past and Future and the Hoosier Oncology Group Nasser Hanna, MD Associate Professor Indiana University IU Simon Cancer Center Chairman, Hoosier Oncology Group

2. Volunteering and Service �A civilization flourishes when people plant trees under which they will never sit� Greek Proverb

3. Scope of the problem in the U.S. 1.4 million people will be diagnosed with cancer this year More than 560,000 people will die from cancer this year Second leading cause of death behind heart disease 1 in 3 women will get cancer in their lifetime Breast: 1 in 8; Lung: 1 in 16; Colon 1 in 19 1 in 2 men will get cancer in their lifetime Prostate: 1 in 6; Lung 1 in 13; colon 1 in 18

6. To understand where we go from here, we must first understand where we have come from

7. The Initial Study of Cancer Oldest description of cancer dates back to 1600 BC: �breast ulcers� cauterized with a �fire drill� 2nd century, Galen declared that cancer, caused by excess �black bile�, was incurable thought prevailed for the next 1000 years 1761, Giovanni Morgagni studied autopsies and described macroscopic findings of cancer 1846, advent of anesthesia allowed for cancer surgery 19th century, Rudolph Virchow studied microscopic details of cancer

8. The first cancer therapies 1878, Thomas Beatson observed that oopherectomy resulted in cessation of breast milk production Charles Huggins reported orchiectomy caused prostate cancers to shrink 1896, Wilhelm Roentgen invented the x-ray machine

9. The systemic approach to cancer Cancer therapies of 20th Century discovered largely by serendipity Mustard gas exposure to naval personnel led to myelosuppression birth of alkylating agents Folates caused leukemic cells to grow Sidney Farber evaluated anti-folates against leukemia led to methotrexate (MTX) 1956�1st cure of metastatic cancer�choriocarcinoma with MTX

10. �Modern� Chemotherapy Vinca alkaloids derived from the Madagascar periwinkle during a screen for diabetic drugs 1955, NCI developed the first cancer cell lines and animal models to study cancer 100,000�s of compounds screened 1964�taxanes discovered from the yew tree 1966�camptothecans from chinese ornamental tree Platinum discovered while evaluating the electric field effect on bacterial growth Bacterial stopped dividing caused by the platinum on the electrodes 1973, �War on Cancer� is declared

11. Cooperative Group Structure NCI-supported groups NCCTG SWOG ECOG SECSG RTOG CALGB NSABP LCSG GITSG

12. Why is progress not faster? Pre-clinical models are unreliable Clinical trials take too long to initiate and complete Too few participants Trials designed for incremental gains due to a poor understanding of the complex biology of the disease Sources of funding limit research Lack of cooperation, etc.

13. Research Opportunities Most community practices lacked the infrastructure to conduct research Patient access to university cancer care limited by logistics HOG was conceived in 1984, modeled after the NCCTG Indiana University as the research base Indiana community physician partnerships Research, Infrastructure/training, Education

14. The Hoosier Oncology Group (HOG) A non-profit, 501(c)3 cancer research organization Maintains infrastructure to facilitate research from hypothesis to publication

15. HOG HISTORY Subsidiary of the Walther Cancer Institute 1984-2007 Initiated well over 100 trials enrolling thousands of subjects Fostered collaboration between the private sector, other research organizations, and academic centers

16. Results of Success Reputation as a research organization that efficiently and accurately evaluates the activity of new anti-cancer therapies

19. Quality of Life Prozac vs Placebo Only study to evaluate placebo-controlled, phase III trial in cancer population Testing anti-emetics Olanzapine (without dexamethasone) is highly effective in reducing delayed N/V in moderately to highly emetogenic regimens

20. Small cell lung cancer VIP better than EP in ED SCLC VIP + oral VP-16 not better than VIP alone in ED SCLC

21. Phase III Study of Cisplatin Plus Etoposide or IrinotecanHanna et al JCO 2006

22. Overall Survival

23. Non-small cell lung cancer Single agent cisplatin/XRT not better than XRT in stage III NSCLC Cisplatin/Gem better than Cis alone in stage IV NSCLC Pemetrexed comparable to Docetaxel in 2nd line NSCLC

24. ChemoRT Cisplatin 50 mg/m2 IV d 1,8,29,36Etoposide 50 mg/m2 IV d 1-5 & 29-33Concurrent RT 59.4 Gy (1.8 Gy/fr) HOG LUN 01-24/USO 02-033Hanna et al, JCO 2007

25. Cisplatin/Etoposide/XRT +/- Docetaxel in Stage III NSCLC

26. Hoosier Oncology Group, Inc. Present Day

27. Hoosier Oncology Group Incorporated July 2007 Supported by grants from NCI, DOD, Walther Cancer Institute Endowed funds from charitable contributions Capacity to run investigator (primarily) and industry initiated trials

28. HOG�s growing strength Funding increases and capacity improvements on an annual basis 21 active trials in diverse disease sites The place to go for quick phase II trials Lacks the inefficiencies of many cooperative groups Loyal and dedicated staff of 21 Easily adaptable to changing research environment Our studies request NO unfunded mandates HOG answers important and fundamental questions in oncology Honest brokers of research Avoid marketing studies

29. What obstacles HOG AVOIDS Procedural (policies�occur in group but also within NCI, NIH, CTEP, CIRB, US FDA, pharmaceutical industry) Structural (multiple participants in process, with independent needs to move forward), infrastructural (approval needed from one system to move to another) Synchronicity (protocol devo, contracts, drug acquisition, etc. occur within different groups)

30. Why efficiency matters Trial design frequently becomes obsolete Rapidly changing nature of cancer care Investigators become discouraged Sites become disinterested

31. Hoosier Oncology Group Clinical Trial Working Groups led by national leaders in their fields. Target Diseases: -Thoracic -Breast -GI -GU -GYN -Hematology -QoL/Symptom Control -Head & Neck

32. HOG: One Stop Shop Study Start Up Growing network of community sites and academic centers 200 community and 125 academic physicians representing over 40+ community and academic sites in the US International sites including Peru, UK, Canada and Australia

34. HOG Academic Partners Academic: Indiana University Simon Cancer Center Washington University Medical Center in St. Louis Rush-Presbyterian University of Chicago UT Southwestern Medical Center at Dallas Northwestern University Feinberg School of Medicine Fox Chase Cancer Center University of Nebraska Medical Center University Hospitals of Cleveland Baylor University Houston Medical University of South Carolina Royal Adelaide Hospital Cancer Centre Oregon Health Science University Royal Hospital London-Barts

35. DoD - Center of Excellence for Individualization of Therapy for Breast Cancer Clinical Trial Core Miller/Sledge: IU Clinical Research Office HOG Patient Advocacy Core Mary Lou Smith: Research Advocacy Network Biostatistics & Data Management Core Changyu Shen: IU Pathology Core Ann Thor: Colorado Genomics Core Jenny Chang: Baylor/Houston Proteomics Bob Hickey: IU Pharmacogenetics & Pharmacogenomics Core Leyland-Jones: Montreal HOG created tracking system which allows us to know where any given sample is at any give time.HOG created tracking system which allows us to know where any given sample is at any give time.

36. The Vision of the HOG Unparalleled community-academic partnerships Cancer Research Physician/Nurse education Patient Advocacy/Outreach

37. Mission Statement To reduce the burden of cancer through the conduct of high quality research and education, as guided by the collaborative efforts of the IU Simon Cancer Center, academic physician scientists, community cancer investigators, and patient advocates.

38. What can patient representatives do in the HOG?

39. Patient Committee Led by Patient representative from the Board Recruits from patient advocates, Board members, sites, other Review patient issues/initiatives such as accrual to studies, ICS, fundraising, collaborate with other groups (RAN, etc.) Quarterly mtg with HOG staff advocate Meet bi-annually at CTWG mtg Bi-annual report to Board (written or in-person)

40. Research Partnerships Committee Led by Executive Director Members include: Chief Community officer; Chairman of Board; other Board members; patients; assistance via Emeritus Board prn Interacting with current and future research partners along with HOG staff point person Phone calls, lunches, site visits Engage new relationships (MCCRC, Fox, Arkansas, GU consortium, etc.)

41. Scientific Oversight Committee Led by Chief Medical Officer Composition reflects HOG �values� for research Chief Community Officer or other community oncologist (can be non-Board member) Patient representative Statistician HOG Proj Mgr. Leader Review (via conf call approx q2mo) scientific integrity of trials, potential for peer review funding, IIT vs IST, ability to complete trial, financially neutral or better or justify if not, community support Review/approve LOI�s and protocols

42. �Life�s most persistent and urgent question is, �What are you doing for others?�-Dr. Martin Luther King, Jr.

43. What can you do? Hold elected officials accountable for cancer research funding and prevention programs Hold elected officials accountable to enhance prevention Indiana receives $600 million/yr from tobacco taxes and the Master Settlement Agreement Spends $10 million on tobacco control Spends $2 BILLION on tobacco-related disease Demand that research monies are well spent by the pharmaceutical industry, academia, and the NCI Encourage patients to enter clinical trials Demand physicians participate in clinical trials Join the HOG Board as a patient advocate Lead the Patient Committee Serve on the Scientific Oversight Committee Serve on the Research Partnerships Committee Never, Never, Never lose sight of PREVENTION

44. Tobacco: The Facts in the U.S. Causes more deaths than alcohol use, car crashes, suicide, AIDS, homicide and illegal drug use COMBINED 20% of all U.S. deaths 50% of all lifetime smokers 30% of ALL cancer deaths

45. Tobacco: A Global Genocide Over 1 billion smokers in the world today 1.6 billion by 2025 300 million in China consume 1.7 trillion cigs/yr 10 million cigarettes sold every MINUTE 100,000 kids start EVERY DAY 20% of teens age 13-15 50% will smoke at least 15-20 years 500 MILLION of all living people TODAY will die due to tobacco Entirety of North AND Central America COMBINED Someone dies every 8 SECONDS

46. The Tobacco Market Controlled by just a few corporations in U.S., Japan, Great Britain Phillip Morris controls 50% of U.S. �market� 50% of all tobacco co. expenditures goes to promotional allowances and items T-shirts, lighters, key rings, etc. 50% of young people in the world live in developing nations where they can get free cigarettes 12% of all Chinese gov�t revenues 40% of all TV/radio ads in Russia

47. The key events in 2009 to reduce the future suffering from cancer came from ADVOCATES, NOT DOCTORS

48. 2009 Achievements The single most important occurrence in 2009 to reduce the suffering and death from lung cancer SCHIP legislation Increased cigarette tax will result in 2 million fewer smokers Most important health policy to impede the tobacco cartel in the U.S. FDA regulation of tobacco products

49. A final word� �The future depends on what we do in the present� �Mahatma Ghandi

50. www.hoosieroncologygroup.org