Melanoma Symposium Los Angeles, CA - January 16, 2010.Jim Breitfeller

Los Angeles, CA - January 16, 2010

Leading melanoma experts will discuss emerging therapies, the importance of clinical trials, and innovations in research. A Q&A Session will follow.

Melanoma Symposium Los Angeles, CA - January 16, 2010



Take Care,

Jimmy B

Educational Teleconference: Update on Immunotheraphy of Melanoma - July 15, 2009..Melanoma..Jim Breitfeller

Please save this date!!!!!
Educational Teleconference: Update on Immunotheraphy of Melanoma - July 15, 2009

The teleconference will focus on the latest information on immunotherapies of melanoma. Whether you are newly diagnosed or are years after diagnosis, this program will provide quality information about melanoma. The conference is intended for patients with melanoma or friends or family member so that you have the information you need to understand melanoma from diagnosis, to treatment, to long term follow up.



Speaker: Jedd Wolchok, M.D., Ph.D.

Moderator: Lynn Schuchter, M.D.



Join us for a free teleconference, Update on Immunotherapy of Melanoma, from 1:00 pm to 2:00 pm Eastern Standard Time (EST) on July 15, 2009. After Dr. Wolchok’s presentation, there will be time for live question and answer period.



Dr. Jedd Wolchok, is an Assistant Attending Physician at Memorial Sloan-Kettering Cancer Center. Dr. Wolchok is a member of the faculty of Memorial Sloan-Kettering Cancer Center with expertise in the treatment of metastatic melanoma. His specific research interest is novel immunologic therapies and he has been involved in the development of the DNA vaccine program at every level, from pre-clinical studies in mouse models through clinical trials. He has authored numerous articles concerning DNA vaccines and clinical care of melanoma, and he co-authored two chapters in the definite textbook, Cutaneous Melanoma. Dr. Wolchok received his advanced education at New York University where he earned an M.D. as well as a Ph.D. in microbiology.


Dr. Lynn Schuchter is a Professor of Medicine. She is the Director of the Melanoma Program at the Abramson Cancer Center of the University of Pennsylvania as well as the Director of the Clinical Research Unit at the Cancer Center. Dr. Schuchter’s research focuses on a new approach to cancer treatment for patients with melanoma known as molecularly targeted therapy. Dr. Schuchter is also involved with numerous cancer vaccine trials. She is the Co-Principal Investigator of the Skin Cancer SPORE grant at the University of Pennsylvania/Wistar Institute. Dr. Schuchter completed her oncology fellowship at the John’s Hopkins Cancer Center. She joined the faculty of the University of Pennsylvania in 1989. Dr. Schuchter is on the Melanoma Research Foundation Board and is the Chair of the Scientific Advisory Board for the MRF.

After the presentation, Dr. Wolchok will answer your questions.

source:http://www.melanoma.org/upload/2142.pdf


Take Care,

Jimmy B

State of the Science Lecture Series On Melanoma ..Jim Breitfeller

If you want, you can dive into these Lectures on Melanoma

http://www.webtie.org/SOTS/Meetings/Melanoma/05-05-2003/lectures.htm
State of the Science Lecture Series On Melanoma


Jimmy B

Follow Up of Dr. Flaherty’s Conference Call on Targeted Therapy Melanoma..Jim Breitfeller

As we all know Melanoma is on the rise in the United States and 65000 will be diagnosed this year alone. 8400 will die of the disease. Despite 30 years of research in Melanoma, we only have two FDA approved drugs at the present for Metastatic Melanoma. One is Dicarbazine also known as DACARBAZINE... NSC-45388, TOSLAB 25071, DICARBAZINE, DACARBAZINE RELATED COMPOUND A 5- AMINOIMIDAZOLE-4-CARBOXAMIDE HCL USP(CRM STANDARD), DACARBAZINE USP STANDARD, (DTIC).

It is usually administered as a single agent and has a clinical response of 5 to 10 percent. Part of the major problem is that the Melanoma Cells can become chemical resistant to the therapy because the cells can morph based on their microenvironment.1

The United States Food and Drug Administration (FDA) officially recognized the efficacy of Interluekin -2 (IL-2) in patients with metastatic melanoma by granting approval for commercial marketing of the drug for that indication in 1998, based on tumor response and survival data generated from clinical trials of the intermittent high-dose bolus regimen.

Today, we are in a new era of therapy. Immunotherapy has come to the forefront of Melanoma Therapy. Researchers are beginning to crack the code and are making great strides inmmunotherapy.

To be able to unravel the “Melanoma Maze” as I call it, we need to know “How Melanoma works.” In this next section, It may get very detailed, but I will try to explain with the help of the experts and a dictionary. I am learning like you so please bear with me.

So here it goes!!!!!

Cancer begins in cells, the building blocks that make up tissues. Tissues make up the organs of the body. Normally, cells grow and divide to form new cells as the body needs them. When cells grow old, they die, and new cells take their place.
Sometimes this orderly process goes wrong and new cells form when the body does not need them, and old cells do not die when they should. These extra cells can form a mass of tissue called a growth or tumor. Not all tumors are cancer.
In Melanoma, the cause is by the uncontrolled, unregulated growth of Melanocytes. The cell cycle proceeds unregulated, and cell growth proliferates.



It has been suggested that there are Five Stages to Metastatic Melanoma .2
Five stages of tumor progression have been suggested:
1) Benign melanocytic nevi- Melanocytic nevi are benign neoplasms or hamartomas composed of melanocytes, the pigment-producing cells that constitutively colonize the epidermis. The malignant analogue of a melanocytic nevus is melanoma. This where Melanoma can start, but can also start at eyes, ears, GI tract, leptomeninges, and oral and genital mucous membranes and even sometimes the primary site is unknown and is called “Occult Primary Melanoma”.

2) Melanocytic nevi with architectural and cytologic atypia (dysplastic nevi) “An atypical nevus, usually larger than 5 millimeters in diameter with variable pigmentation and ill-defined borders, marked by melanocytic dysplasia and associated with an increased risk for the development of nonfamilial cutaneous malignant melanoma. Also called dysplastic nevus3” The Precursor to melanoma.
“The sequence of events in which normal melanocytes transform into melanoma cells, referred to as melanomagenesis, is poorly understood. It likely involves a multistep process of progressive genetic mutations that (1) alter cell proliferation, differentiation, and death and (2) impact susceptibility to the carcinogenic effects of ultraviolet radiation.4”

3) Primary malignant melanoma, radial growth phase
This is early pattern of growth of cutaneous malignant melanoma in which tumor cells spread laterally into the epidermis. This is where if it is identified and removed with surgery, there is 95 % cure rate. The Melanoma Cells have not entered into the lymphatic system.

4) Primary malignant melanoma, vertical growth phase
The late pattern of growth of cutaneous malignant melanoma in which tumor cells spread from the epidermis into the dermis.


Figure 1. Human Skin5

5) Metastatic malignant melanoma
Each step in tumorigenesis is marked by a new clone of cells with growth advantages over the surrounding tissues. The cancer, as it invades in its place of origin, may also work its way into blood vessels. If this occurs, it provides yet another route for the cancer to spread to other organs of the body. When the cancer spreads elsewhere in the body, it has become systemic in extent and the tumor growing elsewhere is known as a metastasis.

What are the different Types of Malignant Melanoma?
1) Superficial spreading melanoma
2) Nodular melanoma
3) Lentigo maligna melanoma
4) Acral melanoma.
5) Ocular Melanoma

Superficial spreading melanoma does just as it sounds. It is on the surface of your skin and spreads horizontally. It is the most common and is a bout 65% of the Melanoma reported cases.

Nodular melanoma is a much less common form of melanoma. It usually starts as a raised lesion that is dark black-blue or bluish-red, however some can lack color. Nodular melanomas account for approximately 15% of cases. It is fast spreading and usually grows vertically in both directions.

Lentigo maligna melanoma is usually found on the palms of the hands, soles of the feet and/or around the toenails. 5-15% of all cases

Acral melanoma is an uncommon type of melanoma. It is the most common type seen in nonwhite individuals. It usually occurs on the palms and soles. Sometimes it occurs on the vulva and vagina. Acral melanoma accounts for 5% of Melanoma cases.

Ocular melanoma occurs in the eye and is estimated that 2% of the total melanoma diagnosed per year is ocular.

So where do we go from here?

Since we now know that the cause for this unregulated growth of Melanocytes is mutation in certain genes, we need to know the signaling pathways that cells took to grow. So researchers like Dr. Smalley, Dr Herlyn and many others have recently identified that the activating mutation in the BRAF gene on chromosome 7 linked to 60% of the cases in Melanoma.6

“This gene encodes a protein belonging to the raf/mil family of serine/threonine protein kinases. This protein plays a role in regulating the MAP kinase/ERKs signaling pathway, which affects cell division, differentiation, and secretion.

Mutations in this gene are associated with cardiofaciocutaneous syndrome, a disease characterized by heart defects, mental retardation and a distinctive facial appearance. Mutations in this gene have also been associated with various cancers, including non-Hodgkin lymphoma, colorectal cancer, malignant melanoma, thyroid carcinoma, non-small cell lung carcinoma, and adenocarcinoma of lung.”7

Our understanding of B-RAF regulation was greatly increased recently when the crystal structure of the B-RAF kinase domain bound to the small molecule inhibitor BAY43-9006 was solved (Wan et al., 2004).

So in 2006, in Cancer Research 66, 1611-1619, February 1, 2006], A research paper came out entitled: The Raf Inhibitor BAY 43-9006 (Sorafenib) Induces Caspase-Independent Apoptosis in Melanoma Cells. David J. Panka1, Wei Wang2, Michael B. Atkins1 and James W. Mier1
1 Division of Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School and 2 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts
The paper caused excitement among researchers in that Raf Inhibitor was a way to block the pathway and cause apoptosis in Melanoma. This is a form of cell death in which a programmed sequence of events leads to the elimination of cells without releasing harmful substances into the surrounding area.

So what are the signaling pathways known to date?

Figure 2. Signaling pathways affected by the common primary changes in human melanoma, and some inter-relationships8


“Molecules shown in bright red are those clonally amplified or activated in some melanomas; those in bright blue are clonally deleted or inactivated in some melanomas. Pale red and pale blue indicate proteins that are at least secondarily upregulated or downregulated in melanoma, respectively. Rectangles indicate transcription factors. Some components have a larger outline; this is just to emphasize apparently important signaling nodes, and does not reflect molecular size.”
Attempts have been made to focus on pathways known to be present and active in melanoma cells (Dr. Smalley, Dr. Herlyn), although some sections of pathways are derived from the broader literature, and with the help of the pathway maps of Weinberg.9

Figure 3. Schemic of known active signaling pathways in Melanoma
by Dr. Smalley and Dr. Herlyn6




As you can see, from the diagrams, some of these pathways are intertwined and make the research more difficult but not impossible. Careful planning of the experimentations may yield new target therapies down the road. There may be a combo of Chemo and Immunology together to stabilize the Melanoma Beast.

So Now, Where does the Patients come into play?
We need to start by having our Blood typed for Biomarker. A biological marker, or biomarker, is a phenotypic parameter (eg, a substance, structure, or process) that is measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. This step One. Step two is the biopsy of your tumor and getting it typed/mapped. If the Oncologist can get the pathway that is mutated, They will be able to direct to the right therapy base on that mutation.

Example: Kit Mutation
“THURSDAY, April 17 2008 (HealthDay News) -- The cancer drug Gleevec has forced metastatic melanoma into remission for the first time, report researchers at the Dana-Farber Cancer Institute in Boston.
The case involves a 79-year-old woman with melanoma tumors in several parts of her abdomen. The tumor cells carried an abnormality in a gene called KIT, so the patient was enrolled in a clinical trail of the drug imatinib (Gleevec), which targets the KIT gene.
Four weeks after the woman started therapy, there was dramatic reduction in tumor size and metabolism. Two of the tumor masses had vanished, and several others were much smaller. After four months, the tumors were still in check and, nine months later, the women was still taking the drug and her condition remained stable.
The report was published in the April 20 issue of the Journal of Clinical Oncology .
"This is the first proof of principle that we can find an Achilles' heel in melanoma and by targeting that gene with a drug, cause the [tumor cells] to die. It is especially exciting because there haven't been any effective treatments for melanoma patients with metastatic disease," study author Dr. Stephen Hodi said in a prepared statement.
He said this case may involve just one patient, but should inspire new hope in the fight against melanoma. Because previous research failed to identify any genetic weak point that could be targeted to stop melanoma cell growth, some researchers believed that no such Achilles' heel existed for melanoma cells. The discovery of this one suggests there may be others.”
SOURCE: Dana-Farber Cancer Institute, news release, April 17, 2008



I believe we are now able to use the molecular profile of disease to deliver the right therapy to the right patient at the right time. But we must first build the infrastructure that will support Targeted Therapy with Personalized Medicine. This will require a Novel approach to the Global Healthcare seen. We would need a seamless communication along with various components including a national tissue repository, molecular diagnostic standards and procedure in place. A network of clinical sites working in collaboration to identify cohorts of patients with similar abnormal molecular profiles that is in a database and is available to Oncologists and Medical Researchers alike, a bioinformatic infrastructure integrating all of these elements.

It may be already here!!!!!!


Big Changes at BiobankCentral

Posted: 27 Jan 2009 10:36 AM CST

by Kate Blenner, Program Analyst, FasterCures10
We at FasterCures are very pleased to announce some big changes to BiobankCentral.org, the Web site we have established to highlight the importance of biobanks to medical research. This site links researchers to resources, encourages the donation of specimens, and educates the public about the benefits of research on banked biospecimens. After interviewing key stakeholders, including patient advocates, biobank operators, and leaders in the field of biospecimen research, we will begin staging some new features and functions that will make Biobankcentral.org even more useful to visitors hoping to learn more about these critical resources.

The first of these new features is the Spotlight on Innovation which will highlight individuals and organizations doing exceptionally innovative work in biobanking. Our first Spotlight focuses on the Susan G. Komen for the Cure® Tissue Bank at the Indiana University Simon Cancer Center, or Komen Tissue Bank (KTB) for short. This bank’s mission is to collect samples of normal, healthy breast tissue and other biospecimens from healthy women for breast cancer research. Yes, you read that correctly—normal tissue. Healthy women.

In its 1998 priorities for cancer research, the National Cancer Institute identified the lack of knowledge about the normal biology and development of the mammary gland as a significant barrier to finding a breast cancer cure. Most research to date has focused on characterizing diseased tissue, but without the frame of reference of how healthy tissue develops and functions opportunities for a cure could be missed. Complicating the issue was a shortage of normal tissue available for study. The NCI’s recommendations to address the ‘tissue issue’ languished for a few years, until some motivated advocates and clinicians at IU Simon Cancer Center decided to form the KTB.

Despite initial skepticism that healthy women would want to go through an invasive collection procedure, KTB put its faith in the motivation of the breast cancer advocacy community—and it paid off. They have collected thousands of samples to date, and communities across the country have asked KTB to set up its collection tent at their local Race for the Cure events. As bank co-founder and patient advocate Connie Rufenbarger told me: “These women have walked, they’ve written checks, they’ve lit candles—they’ve done everything they can to demonstrate they want to help. [The response] really speaks to the fact that there isn’t a whole lot you could ask that women wouldn’t give you to cure this disease.”

I hope you enjoy this first Spotlight of the Komen Tissue Bank as much as I enjoyed speaking with its remarkable founders and staff. If you have a moment, stop by the KTB Web site to find out how you can get involved in their work to find a cure. And, of course, keep an eye on BiobankCentral.org—we have many more exciting new changes to come.



References

1. Cedric Gaggioli and Erik Sahai- Melanoma invasion – current knowledge and future directions Pigment Cell Res. 2007 20; 161–172
2. http://www.clevelandclinicmeded.com/medicalpubs/
3. http://www.answers.com/topic/malignant-melanoma
4. Demierre MF, Nathanson L. Chemoprevention of melanoma: an unexplored strategy. J Clin Oncol. Jan 1 2003;21(1):158-65. [Medline]
5. http://www.mydr.com.au/files/images/categories/skinhair/skinstructure.gif
6. Keiran S.M. Smalley and Meenhard Herlyn Targeting Intracellular Signaling Pathways as a Novel Strategy in Melanoma Therapeutics Ann. N.Y. Acad. Sci. 1059: 1–10 (2005). 2005 New York Academy of Sciences.doi: 10.1196/annals.1339.005
7. http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRAF
8. Dorothy C Bennett- How to make a melanoma: what do we know of the primary clonal events? Division of Basic Medical Sciences, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK.
9. R. A. Weinberg The Biology of Cancer Garland Science, Taylor & Francis Group,. LLC, London, 2007, 864 pp., ISBN-10 0-8153-4078-8/
10. http://www.fastercures.org/

Targeting Immune Stimulation: Clinical Application of Immunology Melanoma ..Jim Breitfeller

Contributing Writers: F. Stephen Hodi, MD and Lauren Cerruto
Contributing Editor: F. Stephen Hodi, MD
Editor-in-Chief: Jeffrey S. Weber, MD, PhD


Efforts to develop immunotherapies for cancer have historically involved vaccines and individual cytokines, which have produced benefits to only a small percentage of patients.

Recently, improved understanding of immune processes, such as the role of T-cell costimulatory molecules and regulatory molecules, has led to renewed efforts to develop immunotherapies to treat cancer. Current clinical trials are utilizing monoclonal antibodies (mAbs) to modulate costimulatory effects in the treatment of a variety of cancers. For example, two fully humanized mAbs that block cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) have advanced to phase III clinical studies in metastatic melanoma. Antitumor activity has been observed in melanoma and other malignancies after treatment with anti-CTLA-4 antibodies, as well as the potential for autoimmune-related toxicities.

Rationale for Targeting CTLA-4 in Patients with Cancer

http://www.livingmedicaltextbook.org/Activity/index.cfm?showfile=b&jn=1843&sj=1843.04

Living Medical Textbook Targeting Immune Stimulation: Clinical Application of Immunology





Jimmy B

Summary of the Conference Call with Dr. Flaherty on 1/21/2008 Melanoma.. Jim Breitfeller

Topic: Targeted Therapy

WHAT IS TARGETED THERAPY?

Targeted therapy is a term that refers to a drug or combination of drugs that targets a specific pathway in the growth and development of a tumor. By attacking or blocking these important targets, the therapy helps to fight the tumor itself. The targets themselves are typically various small molecules in the body that are known or suspected to induce cancer formation.

HOW ARE TARGETED THERAPIES NAMED?

The names of the major classes of targeted therapies typically include the word "anti-", or "inhibitor", together with the name of the target itself. This means that the drug blocks, (is "anti"), that particular target. Then within each class of inhibitors, there is/are the actual drug(s).

It is important to realize that a single drug can have several names, including a generic name and a brand name. This can be confusing because often the generic and brand names are used interchangeably in the literature and the media. This means you need to the names to follow the pathways.

What are the different classes of targeted therapy? In other words, what are the different targets?

There are several pathways that have been studied quite intensively and they are:

Kinase: Defintion …Any of various enzymes (proteins) that catalyze the transfer of a phosphate group from a donor, such as ADP or ATP, to an acceptor

1) Map Kinase : Mitogen-activated protein (MAP) kinases (EC 2.7.11.24) are serine/threonine-specific protein kinases that respond to extracellular stimuli (mitogens) and regulate various cellular activities, such as gene expression, mitosis, differentiation, and cell survival/apoptosis
It was studied early on in the Melanoma Research.



2) PI3-Kinase: PI 3-kinases have been linked to an extraordinarily diverse group of cellular functions, including cell growth, proliferation, differentiation, motility, survival and intracellular trafficking. Many of these functions relate to the ability of class I PI 3-kinases to activate protein kinase B (PKB, aka Akt). The class IA PI 3-kinase p110α is mutated in many cancers. Many of these mutations cause the kinase to be more active. The PtdIns(3,4,5)P3 phosphatase PTEN which antagonises PI 3-kinase signalling is absent from many tumours. Hence, PI 3-kinase activity contributes significantly to cellular transformation and the development of cancer. The p110δ and p110γ isoforms regulate different aspects of immune responses. PI 3-kinases are also a key component of the insulin signaling pathway. Hence there is great interest in the role of PI 3-kinase signaling in Diabetes mellitus.).

Another pathway was the c-Kit: Receptor tyrosine kinases, such as c-Kit, are proteins whose function it is to transduce signals from the environment into the cell leading to complex behaviors such as proliferation, migration, survival and differentiation. Many of these behaviors are deregulated in cancer, which is characterized by uncontrolled proliferation, insensitivity towards death stimuli, migration of tumor cells away from the primary tumor site and in some cases also block of cellular differentiation leaving the cell in an immature proliferative state. To be able to target these processes it is vital to have a detailed understanding of the receptor function and the downstream pathways activated.

Well, they developed A c-Kit antigen:


.

Example of Targeted Therapy:

THURSDAY, April 17 2008 (HealthDay News) -- The cancer drug Gleevec has forced metastatic melanoma into remission for the first time, report researchers at the Dana-Farber Cancer Institute in Boston.
The case involves a 79-year-old woman with melanoma tumors in several parts of her abdomen. The tumor cells carried an abnormality in a gene called KIT, so the patient was enrolled in a clinical trail of the drug imatinib (Gleevec), which targets the KIT gene.

Four weeks after the woman started therapy, there was dramatic reduction in tumor size and metabolism. Two of the tumor masses had vanished, and several others were much smaller. After four months, the tumors were still in check and, nine months later, the women was still taking the drug and her condition remained stable.
The report was published in the April 20 issue of the Journal of Clinical Oncology .

"This is the first proof of principle that we can find an Achilles' heel in melanoma and by targeting that gene with a drug, cause the [tumor cells] to die. It is especially exciting because there haven't been any effective treatments for melanoma patients with metastatic disease," study author Dr. Stephen Hodi said in a prepared statement.
He said this case may involve just one patient, but should inspire new hope in the fight against melanoma. Because previous research failed to identify any genetic weak point that could be targeted to stop melanoma cell growth, some researchers believed that no such Achilles' heel existed for melanoma cells. The discovery of this one suggests there may be others.

SOURCE: Dana-Farber Cancer Institute, news release, April 17, 2008Melanoma Mutations:

Strategies for attacking melanoma may soon involve a personalized approach based on the genetic characteristics of the patient’s tumor. Recently, scientists have begun to uncover genetic mutations that drive the unchecked growth of melanoma cells. By determining the pathways that caused the mutation, they hope to create drugs that better target the specific problem.

A common genetic mutation in melanoma creates an overactive version of a protein called BRAF, which instigates cell growth and division. Other mutations activate a related protein, called N-RAS, also resulting in unchecked cell division. Drugs designed to block these overactive proteins kill melanoma cells in laboratory tests, but so far they have shown only some promise in patients. So they are starting personalize the therapy base on patient’s tumor genetics.
Near term goal is to control the progression until they can find the silver bullet. So they will use Chemo and Biological to control the Beast for now.


So, hold on to your hats and make sure that if you have a tumor that can be harvested, you should ask your oncologist to get genetic mapping/typing of the tumor. It could send you down the YELLOW BRICK ROAD to the Emerald City.

Another take away is that a cure may be based on personalized therapy. So there might not be just one cure, but many based on genetics.

Source:Oncolink and the Dictionary

Take Care

jimmy B

Educational Teleconference - Cancer Care: New Advances in Melanoma Jim Breitfeller

Date: 1/21/2009
Contact: education@melanoma.org


This teleconference will focus on the new advances in treatment for melanoma. Whether you are newly diagnosed or are years after diagnosis, this program will keep you up-to-date on the new treatments available to melanoma patients. The conference is intended for patients with melanoma along with their friends, or family members.



Speaker: Dr. Keith Flaherty, Assistant Professor of Medicine, Abramson Cancer Center of the University of Pennsylvania



Moderator: Dr. Lynn Schuchter, Professor of Medicine, Abramson Cancer Center of the University of Pennsylvania



Join us for a free teleconference, Cancer Care: New Advances in Treatment, from 12:00 pm to 1:00 pm Eastern Daylight Time (EDT) on January 21, 2009. After Dr. Flaherty’s presentation, there will be time for live question and answer period.

Melanoma Educational Teleconference


Click on link and register today.
I have read some of Dr. Flaherty's papers

Description of Research Expertise
Experimental therapies

Description of Clinical Expertise
Melanoma
Renal cell carcinoma

Selected Publications
Flaherty KT, Malkowicz SB, Vaughn DJ: A Phase I Study of Weekly Liposome-encapsulated Doxorubicin in Patients with Advanced, Androgen-independent Prostate Cancer. Am J Clin Oncol. 27(2): 136-9, Apr 2004.

Flaherty KT, Stevenson JP, Redlinger M, Giantonio B, Algazy KM, O’Dwyer PJ: A Phase I, Dose Escalation Trial of ZD0473, a Novel Platinum Analogue, in Combination with Gemcitabine. Cancer Chemother Pharmacol. Jan 29 2004.

Bilenker JH, Stevenson JP, Flaherty KT, Algazy K, McLaughlin K, Haller DG, Giantonio BJ, Koehler M, Garcia-Vargas JE, O'Dwyer PJ. : Phase I trial of the antifolate ZD9331 in combination with cisplatin in patients with refractory solid malignancies. Cancer Chemother Pharmacol. 53(4): 357-60, Apr 2004.

Flaherty KT: New molecular targets in melanoma. Curr Opin Oncol. 16(2): 150-4, Mar 2004.

Flaherty KT., Stevenson JP., Hahn SM., Redlinger M., O'Dwyer PJ.: Phase I combination trial of gemcitabine, paclitaxel, and carboplatin in patients with advanced malignancy. Cancer Chemotherapy & Pharmacology 52(3): 217-22, Sep 2003.

Flaherty KT., Stevenson JP., Gallagher M., Giantonio B., Algazy KM., Sun W., Haller DG., O'Dwyer PJ.: Dose escalation study of tezacitabine in combination with cisplatin in patients with advanced cancer. Cancer 97(8): 1985-90, Apr 15 2003.

Flaherty KT, Tuveson D, Brose M, Rosen M, Lee RJ, Schwartz B, Schuchter LM, O’Dwyer PJ: Pharmacodynamic Study of BAY 43-9006 in Patients with Renal Cell Carcinoma and Melanoma. NCI-AACR-EORTC 2003, poster #A84. 2003.

Flaherty KT, Lee RJ, Humphrey R, O’Dwyer PJ, Schiller J: Phase I trial of BAY 43-9006 in combination with carboplatin and paclitaxel. ASCO 2003, oral presentation, abstract #2854 2003.

Flaherty KT, O’Dwyer PJ: Phase II trials: Conventional Design and Novel Strategies in the Era of Targeted Therapy. Anticancer Drug Development Guide. Teicher BA (eds.). Feb 2003 Notes: In press.

Tao J., Flaherty K., Bagg A.: Unusual hematologic malignancies. Case 1. Hematologic malignancy presenting with diarrhea and bony lesions: systemic mastocytosis. Journal of Clinical Oncology 20(17): 3737-9, Sep 1 2002.


Last updated: 08/20/2007
The Trustees of the University of Pennsylvania





Jimmy B