Cancer ConsultAn Update for Physicians from Cleveland Clinic Taussig Cancer Institute | Spring | 2008

G1P3 antagonizes TRAIL-induced apoptosis in human myeloma cells 2

The Leukemia & Lymphoma Society and Cleveland Clinic Announce Partnership 3

The State of Myelodysplastic Syndrome (MDS) Treatment 4

Cancer Genomics Research Endowed Chair to be Established 6

Taussig Cancer Institute Views 8

Also In This Issue:

Feature Story: Translating Acute Leukemia Research from Bench-to-Bedside

Cancer Consult provides information from Cleveland Clinic Cancer Institute specialists about innovative research and diagnostic and management techniques.

Please direct correspondence to Brian Rini, MD, Medical Editor rinib2@ccf.org

Taussig Cancer Institute/R35 Cleveland Clinic 9500 Euclid Avenue Cleveland, OH 44195

Cleveland Clinic Taussig Cancer Institute annually serves more than 26,000 cancer patients. More than 250 cancer specialists are committed to researching and applying the latest, most effective techniques for diagnosis and treatment to achieve long-term survival and improved quality of life for all cancer patients. Taussig Cancer Institute is part of Cleveland Clinic, an independent, not-for-profit, multispecialty academic medical center.

Cancer Consult Editorial Board Brian Rini, MD, Medical Editor

Derek Raghavan, MD, PhD, Director, Taussig Cancer Institute

Brian Bolwell, MD, Chairman, Hematologic Oncology and Blood Disorders

Robert Dreicer, MD, Chairman, Solid Tumor Oncology

Timothy Spiro, MD, Chairman, Regional Oncology

John Suh, MD, Chairman, Radiation Oncology

Gene Barnett, MD, Director, Brain Tumor and Neuro-Oncology Center

Eric Klein, MD, Head, Urologic Oncology, Glickman Urological and Kidney Institute

Managing Editor Ann Bungo

Art Director Michael Viars

Taussig Cancer Institute Administrator Kim Bell, BSN, MBA

Senior Marketing Manager Lori Schmitt, RN

Cancer Consult is written for physicians and should be relied upon for medical education purposes only. It does not provide a complete overview of the topics covered and should not replace the independent judgment of a physician about the appropriateness or risks of a procedure for a given patient.

© 2008 The Cleveland Clinic Foundation 07-CNR-041

clevelandclinic.org/cancer

Cancer Consult | Spring | 2008

F E A T U R E S T O R Y

Edward A. Copelan, MD copelae@ccf.org

Program Update:Translating Acute Leukemia Research from Bench-to-Bedside

Edward A. Copelan, MD, director of the Acute Leukemia Program at Cleveland Clinic Taussig Cancer Institute, has a vision: Applying advances in molecular genetics to improve patient outcomes.

“We want to incorporate the newest basic research advances into conducting cutting-

edge, translational clinical studies – in hopes of being able to provide our patients with

the best options and the best chance for cure,” says Dr. Copelan, who recently

completed his first year leading the program.

An international expert on bone marrow and stem cell transplantation in leukemia, Dr.

Copelan was recruited from the James Cancer Hospital at Ohio State University and

hit the ground running. His wide-ranging goals for the Acute Leukemia Program

include several major research components.

Utilizing sophisticated genetic testingOne key area of investigation for the program, he says, is the application of basic work on

molecular genetics of acute myelogenous leukemia (AML) to patient care. Although the

root causes of the disease are not yet fully understood, several genetic mutations that are

involved in its pathogenesis have been identified and documented. Many of these can be

detected by standard analysis of chromosomes, but nearly 50 percent of patients have no

abnormalities detectable with standard test. More sophisticated genetic testing, including

techniques pioneered at Cleveland Clinic, can detect mutations undetectable by standard

approaches such as in FMS-like tyrosine kinase 3 (FLT3) and nucleophosmin (NMP1).

“The important thing about these mutations is that they provide targets for therapy and

seem to be predictors of whether patients will do well with chemotherapy or might do

better with a bone marrow transplant,” Dr. Copelan says. “For instance, people who are

NPM1-positive but don’t have a mutation in FLT3 are likely to do well with chemothera-

py. With people who are FLT3-positive, independent of what their NMP1 status is,

they’re likely to need a transplant.”

Cancer Consult 1

F E A T U R E S T O R Y

Early identification is essentialFor Dr. Copelan, early identification of these genetic markers

and determination of relapse risk is essential. “People who

have transplants fare better if you do it early. So if you can

identify the people who are going to need a transplant and

you perform transplantation early, you should improve their

chances for success.” To provide proof of this, Dr. Copelan

and colleagues in the Acute Leukemia Program are developing

prospective studies to determine whether using molecular

genetics approaches in treatment decision-making, in fact,

helps improve treatment outcomes.

Further tailoring treatment plansAnother of the program’s areas of focus is developing better

methods to determine treatment risks posed by a patient’s

specific comorbidities: “Every physician looks at a patient and

asks whether he can tolerate the proposed therapy,” Dr.

Copelan explains. “What we’re doing is trying to develop

objective methods, a mathematical analysis of comorbidities.”

The method relies on a comprehensive list of laboratory

studies. “You add one to the other and you get a score, and

it quantitates the risk that patients will have with specific

therapies,” Dr. Copelan says.

Mikkael Sekeres, MD, MS, Hematologic Oncology and Blood

Disorders, has used this type of approach in determining the

appropriate chemotherapy regimen for older adults with

acute leukemia.

Now, Dr. Copelan is incorporating it into treatment decisions

for younger individuals, including transplant decisions.

Through prospective studies, he and his colleagues in the

program will determine whether using this more mathematic

approach improves treatment outcomes.

For more information about research underway in

Taussig Cancer Institute’s Acute Leukemia Program,

contact Dr. Edward Copelan at 216.445.5647 or

at copelae@ccf.org.

2 Cleveland Clinic Taussig Cancer Institute clevelandclinic.org/cancer

G1P3 antagonizes TRAIL-induced apoptosis in human myeloma cells

While patients with multiple myeloma are frequently treated with

IFN-alpha, the effectiveness of this therapeutic is variable. Investigators

at Taussig Cancer Institute recently published a study in the Journal

of Clinical Investigations, which provides a potential explanation as

to why the effectiveness of IFN-alpha treatment varies.

IFN-alpha is thought to kill myeloma cells by increasing the levels of TRAIL, a protein

that causes apoptosis in cancer cells. The research team, including Venu Cheriyath,

PhD, Rachid Baz, MD, Matt Kalaycio, MD and Ernest C. Borden, MD, assessed the

effects of IFN-alpha2b signaling on the apoptotic activity of TRAIL in human myeloma

cell survival.

While TRAIL was one of the most potently induced

genes in myeloma cells following IFN-alpha2b

treatment, less than 20 percent of myeloma cells

underwent apoptosis. The team observed that

24 hours of exposure to IFN-alpha2b antagonized

TRAIL-mediated apoptosis in myeloma cell lines

and fresh myeloma cells from patient bone marrow

aspirates. Further analysis revealed that the anti-

apoptotic effects of IFN-alpha2b were mediated by

upregulation of a protein known as G1P3, which

stabilized mitochondria and thereby inhibited TRAIL-

mediated apoptosis. Although G1P3 was identified

more than 20 years ago by George Stark, PhD and

his colleagues, its function was elusive until now and

this is the first study showing its role in myeloma

cell survival.

These results suggest that distinct effects of IFN-

alpha2b on TRAIL-mediated apoptosis might account

for discrepancies in the effectiveness of IFN-alpha

treatment in individuals with myeloma. Curtailing

G1P3-mediated anti-apoptotic signals could improve

therapies for myeloma or other malignancies.

“This study is one more step forward in learning how to improve efficacy for multiple

myeloma therapies and future studies are needed to determine what therapies may

work better for those who do not respond well to IFN-alpha” says Dr. Cheriyath, who

is a 2008 Scott Hamilton CARES awardee. Dr. Kalaycio added, “This is just one more

way that treatment is becoming more personalized.”

Contact Dr. Cheriyath at cheriyv@ccf.org, Dr. Baz at bazr@ccf.org,

or Dr. Kalaycio at kalaycm@ccf.org or Dr. Borden at bordene@ccf.org

Cancer Consult 3

The Leukemia & Lymphoma Society and Cleveland Clinic Announce Partnership

This innovative collaboration is a unique approach to making

blood cancer clinical trials available to patients in their

community so they can easily have access to the newest

treatments for leukemia, lymphoma and myeloma.

“The challenge of recruiting patients to participate in clinical

trials is one of the greatest obstacles to getting new drugs

approved,” said Louis DeGennaro, PhD, the Society chief

scientific officer. “In fact, less than 5 percent of adult cancer

patients nationally participate in trials.”

Other major barriers to recruiting patients into clinical trials

include patients’ reluctance to leave their own doctors and the

requirement to travel to major cities outside of their communi-

ties to get treatments and participate in trials. Patients also

often view trials as risky.

Cleveland Clinic is uniquely structured to work with the Society

to overcome these hurdles. Taussig has 45 oncologists at its

main campus and another 20 on staff throughout its regional

hospitals in the Cleveland metropolitan area. Patients can easily

participate in the center’s clinical trials while still remaining with

their own doctors. The ability to remain with their own doctors

will also go a long way toward alleviating patients’ fears about

participating in the trials. As a result of the broad reach into the

community, Cleveland Clinic has access to a large volume of

patients, so recruiting for clinical trials will be much easier.

Patients will have access to promising new therapies and will

receive far greater supervision under highly controlled condi-

tions than they would under normal treatment circumstances.

“The beauty of this partnership is that it breaks down barriers

often associated with clinical trial participation,” says John

Sweetenham, MD, Taussig’s Director of Clinical Research.

“The strides made under this partnership will accelerate the

process of developing and delivering new, more advanced

drugs for patients and will allow us to bring these needed

treatments out to people in their own communities without

them having to travel downtown.”

While many national clinical trials are conducted by cooperative

groups – vast networks of physicians, researchers, medical

centers and universities across the country – the Society-

backed Cleveland Clinic program will greatly streamline the

process and expedite the advancement of new drugs, since

the trials will all be conducted by a single clinical center. The

partnership aims to undertake more than six clinical trials over

the next three years, enrolling 100 to 150 patients, increasing

the number of trials typically completed for these types of

cancers in this timeframe.

The Society, which has set as one of its strategic goals the

acceleration of blood cancer therapies by enrolling more

people in clinical trials, has access to new therapies and will

help determine which drugs should be tested. The Taussig

Cancer Institute will help design the trials and administer

them. The organizations will co-fund the effort.

“Bureaucracy is the silent killer in cancer,” says Dr. DeGennaro.

“This partnership will enable us to address many of the serious

bottlenecks that delay the development of new therapies for

blood cancer patients. Our ultimate goal is to get new

treatments to patients faster and save more lives.”

After the three-year pilot, future plans for the program include

potentially extending it to the National Cancer Institute Case

Comprehensive Cancer Center, in which both Taussig and the

Ireland Cancer Center partner.

For more information about The Clinical Trial Center

for Hematologic Malignancies, please visit

lls.org/clinicaltrialcenter or clevelandclinic.org.

In an effort to increase access and participation in clinical trials among adult blood cancer patients,

The Leukemia & Lymphoma Society and Cleveland Clinic Taussig Cancer Institute have launched a

groundbreaking partnership, The Clinical Trial Center for Hematologic Malignancies.

4 Cleveland Clinic Taussig Cancer Institute clevelandclinic.org/cancer

The State of Myelodysplastic Syndrome (MDS) Treatment

Once considered an orphan disease, myelodysplastic syndrome (MDS) now has a rising incidence with an estimated 12,000 to 15,000 new cases diagnosed annually in the United States. This increase can be attributed to increasing life expectancy, as the risk of MDS grows with advancing age.

“Among 70-year-olds, its prevalence is roughly comparable

to that of prostate cancer in elderly men,” says Jaroslaw

Maciejewski, MD, PhD, Head of Experimental Hematology

and Hematopoiesis at Cleveland Clinic Taussig Cancer

Institute. “This, then, truly is an important disease with

significant socioeconomic implications.”

Understanding pathophysiology and therapeutic optionsWhile MDS has garnered a great deal of attention in the last

few years due to both an improved understanding of their

biological mechanisms and the recent U.S. Food and Drug

Administration of three drug therapies, there is still much

more ground that needs to be covered.

Late last year, Taussig Cancer Institute hosted its first

Myelodysplastic Syndrome Summit to provide a forum for

clinical hematologists, medical oncologists and researchers

to discuss the latest in MDS treatment options and the

development of new therapeutics.

Co-directed by Dr. Maciejewski and Mikkael Sekeres, MD,

MS, both of Cleveland Clinic’s Department of Hematologic

Oncology and Blood Disorders, the two-day summit

featured national and international guest faculty and drew

85 attendants.

Among the conference’s conclusions were a recognition of

the growing role of chromosomal abnormalities and the

need to identify new molecular targets that would allow

targeted therapies.

Figure 1: Morphologic features of hematopoietic progenitor cells as shown in a cytocentrifuge preparation of CD34+ cells selected from a peripheral blood stem cell product include high nuclear:cytoplasmic ratio, delicate chromatin with one to several pale nucleoli, and agranular blue cytoplasm. These features are indistinguishable from normal blasts found in bone marrow aspirate smears. By flow cytometry, 97% of the cells in this sample were CD34+. (Wright-Giemsa stain, original magnification 100x)

Figure 2: Cytocentrifuge preparation of CD34+ selected peripheral blood stem cell product. Morphologic features of hematopoietic progenitor cells (arrows) include high nuclear:cytoplasmic ratio, delicate chromatin with one to several pale nucleoli, and agranular blue cytoplasm. These features are indistinguishable from normal blasts found in bone marrow aspirate smears. By flow cytometry, 97% of the cells in this sample were CD34+. A lymphocyte (center) is shown for comparison. (Wright-Giemsa stain, original magnification 100x)

Figure 3: Cytocentrifuge preparation of CD34+ cells selected from a peripheral blood stem cell product. Morphologic features of hematopoietic progenitor cells include high nuclear:cytoplasmic ratio, delicate chromatin with one to several pale nucleoli, and agranular blue cytoplasm. These features are indistinguishable from normal blasts found in bone marrow aspirate smears. By flow cytometry, 97% of the cells in this sample were CD34+. (Wright-Giemsa stain, original magnification 100x)

Upcoming Symposia The Cleveland Clinic Cancer Institute invites physicians from other institutions to attend the following symposia:

C M E S Y M P O S I A

Advancing care through innovative treatmentsCurrently at Taussig Cancer Institute, eight clinical trials

are underway for patients with various subtypes of MDS that

combine approved drugs with novel therapeutics.

We are attempting to determine which combination of

therapies is most likely to achieve a favorable outcome for

each patient, says Dr. Sekeres.

In addition, Taussig Cancer Institute recently became the lead

center in the National Institutes of Health’s Bone Marrow

Failure Disease Consortium (BMFDC), part of the Nationwide

Rare Diseases Clinical Research Network (RDCRN) to address

orphan diseases and neglected conditions.

Through the BMFDC, a number of clinical trials are available

to patients at Cleveland Clinic and its partnering institutions.

More information about the BMFDC is available by visiting

rarediseasesnetowork.org/bmfdc.

Dr. Maciejewski, Head of Experimental Hematology and

Hematopoiesis at Taussig Cancer Institute, specializes in bone

marrow failure syndromes and refractory anemias. Physicians

may reach him at 216.445.5962 or 800.553.5056, or at maciejj@

ccf.org. Dr. Sekeres is a hematologist/oncologist at Taussig

Cancer Institute who specializes in MDS, leukemia and bone

marrow failure syndromes. He can be reached at 216.445.9353

or 800.553.5056 or at sekerem@ccf.org.

“Among 70-year-olds, its prevalence is roughly comparable

to that of prostate cancer in elderly men,” says Jaroslaw

Maciejewski, MD, PhD, Head of Experimental Hematology

and Hematopoiesis at Cleveland Clinic Taussig Cancer

Institute. “This, then, truly is an important disease with

significant socioeconomic implications.”

Understanding pathophysiology and therapeutic optionsWhile MDS has garnered a great deal of attention in the last

few years due to both an improved understanding of their

biological mechanisms and the recent U.S. Food and Drug

Administration of three drug therapies, there is still much

more ground that needs to be covered.

Late last year, Taussig Cancer Institute hosted its first

Myelodysplastic Syndrome Summit to provide a forum for

clinical hematologists, medical oncologists and researchers

to discuss the latest in MDS treatment options and the

development of new therapeutics.

Co-directed by Dr. Maciejewski and Mikkael Sekeres, MD,

MS, both of Cleveland Clinic’s Department of Hematologic

Oncology and Blood Disorders, the two-day summit

featured national and international guest faculty and drew

85 attendants.

Among the conference’s conclusions were a recognition of

the growing role of chromosomal abnormalities and the

need to identify new molecular targets that would allow

targeted therapies.

Cancer Consult 5

May 7, 2008 11th Annual Moll Pavilion Cancer Symposium InterContinental Hotel & Bank of America Conference Center Cleveland Clinic, Cleveland, Ohio

September 3-4, 2008 Colorectal Cancer Summit InterContinental Hotel & Bank of America Conference Center Cleveland Clinic, Cleveland, Ohio

September 5-6, 2008 12th Annual Meeting of Collaborative Group of Americas onInherited Colorectal Cancer InterContinental Hotel & Bank of America Conference Center Cleveland Clinic, Cleveland, Ohio

For more information, including a list of interna-tional programs and online CME topics, please call the Cleveland Clinic Continuing Education Department at 216.444.5696 or 800.762.8173, or log onto clevelandclinicmeded.com.

Research Conference Grand Rounds Area physicians are welcome to attend Cleveland Clinic Cancer Institute Research Conference Grand Rounds. Category 1 CME credit is available. Grand Rounds are held from 8 to 9 a.m. on Fridays from September through June in the Taussig Cancer Institute’s 3rd floor conference room, R3-002.

To be placed on our Grand Rounds mailing list, call 216.444.7924 or 866.223.8100, ext. 47924, or e-mail kralls2@ccf.org. (Please call in advance to check for cancellations.)

Visit us at ASCO Booth #5018 May 31 – June 2 Chicago, Illinois

6 Cleveland Clinic Taussig Cancer Institute clevelandclinic.org/cancer

Cleveland Clinic Lerner Research Institute to Establish Endowed Chair to Expand Cancer Genomics Research

Charis Eng, MD, PhD, Chair of Cleveland Clinic’s Genomic Medicine Institute,

will serve as the inaugural chair holder.

“We are making tremendous strides every day in understanding the genomic

basis of cancer and hope to develop the most accurate markers for the earliest

diagnoses so that preemptive strikes can be made even before the cancer has

started,” Dr. Eng said. “This gift will further our mission and provide us with the

resources we need to continue our work.”

This is the second endowed chair the Hardis family has created. In 2003, the

couple contributed $1.5 million to establish an endowed chair in oncology

research in Cleveland Clinic’s Taussig Cancer Institute.

“We have lost several friends and a close family member to the disease,” the

Hardises said. “We are making this contribution to help researchers as they

work to understand cancer and develop new treatments.”

Stephen is a trustee of the Cleveland Clinic. He serves on the boards of Axcelis

Technologies Inc., Nordson Corp., Progressive Corp., Lexmark International Inc.,

American Greetings Corp., and Marsh and McLennan Companies Inc. In 2001,

he was given the Business Statesman Award from the Harvard Business School

Club of Northeastern Ohio.

Sondra Hardis is an emerita trustee for Ideastream and the Cleveland Free

Clinic. She also is co-chair of the Lerner Research Institute Leadership Board.

Sondra and Stephen Hardis have committed $1.5 million to establish an endowed chair within the Cleveland Clinic’s Lerner Research Institute to further cancer genomics research. The new endowed chair will build upon Cleveland Clinic’s research and physician strengths and help Cleveland Clinic to realize its potential for groundbreaking research, which will rapidly translate into day-to-day patient care.

Charis Eng, MD, PhD

Cancer Consult 7

The five-year grant is being funded by the NIH’s Cancer Institute and Institute of

Child Health and Human Development. It will enable the study of informed consent

at six of the most active Phase I pediatric cancer clinical trial programs in the country.

The Department of Bioethics at Cleveland Clinic will serve as the coordinating center

for data entry and analysis.

The study aims to provide qualitative and quantitative insight into how Phase I trials

and other options, such as hospice or palliative care, are presented to patients and

their families. Researchers will examine what parents and older children understand

from the communication process and how comprehension and decision-making are

influenced by the communication process, incorporating how parental and clinician-

investigator perspectives may vary.

“Communication is one of the most important aspects of practicing medicine and of

doing clinical research,” says Eric Kodish, MD, study Principal Investigator and Chairman

of the Department of Bioethics at Cleveland Clinic. “Better communication will lead to

better care of children with cancer, and the lessons we learn will apply in many other

settings. Long-term, in addition to better understanding the nature of communicating

Phase I trials, we’ll gain a greater understanding of this very complicated issue.”

The study will look at similarities and differences in the informed consent process for

Phase I and Phase III pediatric clinical trials, examining communication, comprehen-

sion and decision-making. A 10-member Parent Advisory Group on Informed Consent

(PAGCIC) will be established to interpret data collected during the study and provide

suggestions on how to improve the communication involved during the informed

consent process for Phase I trials. Advisory members will include parents who

experienced caring for a child with refractory cancer and considered Phase I trial

participation at one of the six research sites.

In addition to Cleveland Clinic, the centers participating in this project include St. Jude

Children’s Research Hospital in Memphis, Tenn.; Children’s Hospital of Philadelphia;

Children’s National Medical Center in Washington, D.C.; Children’s Hospital of

Pittsburgh; Children’s Hospital and Regional Medical Center of Seattle; and the

National Cancer Institute’s Pediatric Oncology Branch.

Cleveland Clinic Receives $3.3 Million From NIH to Study Communication in Phase I Pediatric Cancer Trials

Cleveland Clinic has received a $3.3 million grant from the National Institutes of Health to study the communication and decision-making process that surrounds Phase I or early-stage clinical trials involving pediatric cancer patients for whom other treatments have failed.

8 Cleveland Clinic Taussig Cancer Institute clevelandclinic.org/cancer

Taussig Cancer Institute Views

She underwent split course radiation

treatment using a two-field approach

with 3000 cGy in 10 fractions

followed by 3300 cGy in 11 fx

with IMRT.

By Jerrold Saxton, MD and Mohammad Khan, MD, PhD, Resident

On a two-month follow up she was

noted to have a dramatic response with

resolution of all of her symptoms, along

with significant shrinkage of her tumor.

At a six-month follow up, she continues

to be without symptoms, and is experi-

encing no changes in vision.

This 61-year-old female who presented with a five-week onset of right facial swelling, blurry vision and severe facial

pain. She was found to have a large unresectable poorly differentiated squamous cell carcinoma of the maxillary

sinus and was staged as T4N0M0. Patients with such rare head and neck cancers benefit from the multidisciplinary

care at Cleveland Clinic, which has cure rates higher than nationally quoted averages.

Dr. Saxton is a member of the Radiation Oncology Department at Taussig Cancer Institute.

His special interests include head and neck, colorectal, gynecologic and genitourinary cancers.

Physicians may reach Dr. Saxton at 216.444.5485 or saxtonj@ccf.org.

8/10/07 CT Scan 11/9/07 CT Scan

Breast Cancer

A Randomized Phase III Study of Conventional Whole Breast Irradiation (WBI) Versus Partial Breast Irradiation (PBI) for Women with Stage 0, I, or II Breast Cancer

Betty Obi, MD 216.445.4895

Lung Cancer

Positron Emission Tomography Pre- and Post-treatment Assessment for Locally Advanced Non-small Cell Lung Carcinoma

Gregory Videtic, MD 216.444.9797

A Phase II/III Randomized Trial of Two Doses (Phase III-Standard vs. High) and Two High Dose Schedules (Phase II – Once vs. Twice Daily) for Delivering Prophylactic Cranial Irradiation for Patients with Limited Disease Small Cell Lung Cancer

Gregory Videtic, MD 216.444.9797

Ocular Cancer

Choroidal Indeterminate Melanocytic Lesions: Prompt vs Deferred Treatment: A Multi Center Randomized Study

Arun D. Singh, MD 216.445.9479

For information about the Taussig Cancer Institute, visit clevelandclinic.org/cancer. 9

Select Cleveland Clinic Taussig Cancer Institute Trials | Spring | 2008

Brain Tumors/Metastases

Phase III Trial Comparing Conventional Adjuvant Temozolomide with Dose-Intensive Temozolomide in Patients with Newly Diagnosed Glioblastoma

John Suh, MD 216.444.5574

Sam Chao, MD 216.445.7876

A Phase III Trial Comparing Whole Brain Radiation and Stereotactic Radiosurgery Alone Versus with Temozolomide or Gefitinib in Patients with Non-Small Cell Lung Cancer and 1-3 Brain Metastases

John Suh, MD 216.444.5574

Sam Chao, MD 216.445.7876

Phase I/Phase II Study of Intravenous Infusion of Tetra-o-Methyl Nordihydroguaiaretic Acid (EM-1421) in Subjects with Recurrent High Grade Glioma

David Peereboom, MD 216.445.6068

A Phase I/II Randomized Study of CDX-110 with Radiation & Temozolomide in Patients with Newly Diagnosed GBM

David Peereboom, MD 216.445.6068

The trials above are a partial listing of the many trials open covering all malignancies at

Taussig Cancer Institute. Please call 216.444.7923 for additional listing information.

Prostate Cancer

Phase II Trial of Oral Enzastaurin in Prostate Cancer Patients Who Have Rising PSA (1) During Hormonal Manipulation, and (2) After First-Line Cytotoxic Chemotherapy

Robert Dreicer, MD 216.445.4623

A Randomized, Double-Blind, Placebo-Con-trolled, Phase II Study With and Without Enzastaurin in Combination with Docetaxel and Prednisone, Followed by Enzastaurin Maintenance as First-Line Treatment in Hormone Refractory Metastatic Prostate Cancer Patients

Robert Dreicer, MD 216.445.4623

A Phase III Protocol of Androgen Suppression (AS) and 3DCRT/IMRT vs As and 3DCRT/IMRT Followed by Chemotherapy with Docetaxel and Prednisone for Localized, High-Risk Prostate Cancer

Arul Mahadevan, MD 216.445.8285

Solid Tumor Malignancies

Phase II Study of IMC-1121B in Patients with Metastatic Renal Cell Cancer with Progression on or Intolerance to TKI-Therapy

Jorge A. Garcia, MD 216-444-7774

When Chicago native Ronald Bukowski, MD, first arrived at Cleveland Clinic – fresh out of

medical school at Northwestern University – our campus housed just two buildings and a

couple hundred physicians, and our reputation in the medical field was only beginning to

bloom. Oh, how times have changed. It’s been 41 years since Dr. Bukowski first entered

medicine, blending his passions for both science and people, and now he’s closing a chapter

of his life driven by successes in the fight against kidney cancer and moving on to the next:

retirement. “The idea isn’t to step off the edge of a cliff,” he says. He will continue to partner with colleagues

throughout the country and sit on the FDA Advisory Committee, and he’ll also serve as a consultant to Taussig

Cancer institute. “My wife says I’m going to be busier in retirement than when I was working,” he laughs. But

he leaves with no regrets; after all, by finding medical treatments for cancer that are more effective and less

stressful for patients, he’s accomplished what he set out to do: help make Cleveland Clinic a world-class

organization. “Medicine is a challenge; it’s intriguing – and that’s what really attracts one to this field,”

he reflects. “And you can’t forget that the patient is the most important thing.”

Dr. Ronald Bukowski Retires

9500 Euclid Avenue / AC311 Cleveland, Ohio 44195

clevelandclinic.org/cancer

Dr. Brian Bolwell Named to Fill One of Newly Created Vice Chairman of Professional Staff Affairs PositionsCleveland Clinic recently announced three newly created Vice Chairman of Professional Staff Affairs

positions to enhance clinical operations, support business decisions, and increase efficiencies across

the health system. The creation of these positions supports the Clinic’s move toward its Institutes

Model of care that puts patients first.

The physicians in these roles will work under the Chief of Staff and closely with each of the

Chairman of Cleveland Clinic’s Institutes to focus on business strategy, enhance operations

and improve overall processes.

“Cleveland Clinic has seen continued growth and identified a need for dedicated resources to

support the organization. Great effort has been made to design our clinical programs with the

patient at the center of the care we provide. We’re committed to enhancing patients’ experience

and strengthening physician collaboration,” said Joseph Hahn, MD, Chief of Staff, Office of

Professional Staff Affairs, at Cleveland Clinic. “These new roles will enable us to further that

commitment and better meet the growing needs of our organization and of our patients.”

Brian Bolwell, MD, is a clinical hematologist-oncologist and Chairman of the Department of

Hematologic Oncology and Blood Disorders. In addition, he has been a longstanding member of

the Clinic’s Board of Governors. For more than 10 years, Dr. Bolwell has been chairman of the

Board of Trustees of the Ohio Hematopietic Stem Cell Transplant Consortium.

Also named to the position were Tommaso Falcone, MD, a reproductive endocrinologist and

Chairman of the Department of Obstetrics and Gynecology, and Marc Harrison, MD, a pediatric

intensivist in critical care medicine and Director of Medical Operations.

“Together, Drs. Bolwell, Falcone, and Harrison bring tremendous knowledge, strong work ethics,

and longstanding commitments to the organization that will further the Cleveland Clinic’s overall

business strategy, operations, and processes to the next level. They will work closely with the

physician and executive leadership to continue building an organization that places our patients

first, better utilizes resources, and focuses on providing the highest level of quality care possible,”

Dr. Hahn added.

Brian Bolwell, MD