February 2004

Welcome!

Welcome to the inaugural issue of the Electronic Sarcoma Update Newsletter (ESUN).  We hope that it will be a timely and informative electronic newsletter. We are initiating it to help achieve some of the goals of the Liddy Shriver Sarcoma Initiative, which was formed in December 2003 and will be referred to as The Initiative in this newsletter.

ESUN is published in the spirit of what our logo signifies. The logo for The Initiative (shown in the above masthead) represents sarcoma patients, their caregivers and loved ones, and the medical team working together for a common purpose—to improve the quality of life for those who have sarcoma.  The breaks in the links and between the links are meant to remind us of the difficulties in communication and understanding that often occur among people. The background consists of the small round blue cells that identify one particular type of sarcoma, Ewing’s sarcoma, which is the one Liddy was battling.  To learn more about Liddy, see Liddy’s Story on our website. 

We hope that the articles and the various forms of other information and data that appear in ESUN will empower cancer patients, their caregivers and their loved ones by helping them understand and discuss treatment options with their medical team and to aid them in dealing with this disease.

We are indebted to the members of our Editorial Advisory Board for the assistance with this issue and the encouragement they gave to this project.  We are also indebted to Beverly Shriver and Eva Mae Connell for their extensive proof-reading of this material. To keep our costs to a minimum, ESUN will only be distributed in electronic form.  It will be published bi-monthly.

Please send me your comments and reactions to our efforts.

Bruce Shriver

29 January 2004  ►

 For the Newly Diagnosed

Being told you, a loved one, or a friend has any cancer, let alone one of the types of sarcoma, can be a frightening and stressful experience.  All sorts of questions immediately spring to mind.  "Do people survive this type of cancer?"  "Will I die?" "What will happen to my family?" There is an entire new language to learn—CT Scan, MRI, bone scan, pathology report, chemotherapy, side effects, dosing, radiation therapy and metastasis. The list seems endless. Most important, it would be nice to talk to someone who has gone through what you're about to go through—someone who has "been there". There are a many resources on the web, ranging from medical information to support groups. Each month we will give an overview of some of these resources to help you find a few that you will find useful. We will begin, in this issue by, examining several cancer support organizations.  ►

Annotations by Tom Swartz

CaringBridge

CaringBridge is a nonprofit organization, offering free Web pages to those receiving care. CaringBridge has grown steadily since 1997 and by the beginning of 2003 had hosted more than 10,000 personalized CaringBridge pages, with more than 33 million visits, and more than 1.4 million guestbook entries.  CaringBridge was developed using a unique grassroots approach. This service has developed ties with individuals, the medical community and corporate organizations through word of mouth. Those who visit a CaringBridge page are undeniably impacted. CaringBridge's mission is to bring together a global community of care, powered by the love of family and friends in an easy, accessible and private way. ►

CancerCare

A national non-profit organization whose mission is to provide free professional help to people with all types of cancer through counseling, education, information and referral and direct financial assistance.  Individual counseling and support groups offered online, by telephone, or at on site locations.  Limited financial assistance is available for such items as transportation, child care, home care, and pain medication.  ►

Cancer Hope Network

Provides free, confidential, one-on-one support to people with cancer and their families.  Matches patients with trained volunteers who have themselves undergone a similar experience. ►

Coping with Cancer (National Institutes of Health)

Information about complications/side effects of cancer and its treatment, as well as information on treatment-related nutritional and emotional concerns, supportive care, clinical trials, and end-of-life issues. ►

Carol Jean Cancer Foundation

This foundation offers free recreational support programs for kids with cancer and their families throughout the Maryland, DC and Northern Virginia area.  Its primary program, called “Camp Friendship,” is a special, week-long residential camp for children with cancer, where kids with cancer can just be kids.  Other programs are offered for teens, siblings, and parents. ►

Gilda's Club

The mission of Gilda’s Club is to provide meeting places where men, women and children living with cancer and their families and friends can join with others to build emotional and social support as a supplement to medical care.  Free of charge and nonprofit, Gilda’s Club offers support and networking groups, lectures, workshops and social events in a nonresidential, homelike setting.  Named in honor of comedienne Gilda Radner, there are now some 17 Gilda’s Clubs located throughout the U.S. and Canada. ►

Melissa's Living Legacy Foundation  

A website for teens with cancer who have lots of living to do.  A place where teens can get straight information on cancer and how to deal with cancer issues. Stories from real teens with cancer, and a place where teens can contact other teens through online chat.  Also has sections for Moms and Dads, siblings, and friends. ►

People Living with Cancer

The patient information website of the American Society of Clinical Oncology (ASCO), provides oncologist-approved information on more than 50 different types of cancer and their treatments, clinical trials, coping, and side effects. Additional resources include: a "Find an Oncologist" database, live chats, message boards, a drug database, and links to patient  support organizations. The site is designed to help people with cancer make informed health-care decisions. ►

Planet Cancer

Planet Cancer is a community of young adults with cancer—the ages between "pediatric" and "geriatric."  Planet Cancer focuses on this underserved cancer population. It is a place to share insights, explore fears, laugh, or even, as they put it, “give the finger to cancer with others who just plain get it.” While it does not deny the dark side of cancer, Planet Cancer firmly believes that laughter and light can turn up in the strangest places. ►

R. A. Bloch Cancer Foundation Guide for Cancer Supporters

Various information, articles and links for the patient to best fight cancer.  A guide for cancer supporters, and a state by state register of cancer survivors for various types of cancer. ►

Shared Experience Cancer Support

This site contains a searchable library of the experiences of over 1900 cancer patients.  The library is searchable by categories such as cancer type, diagnosis, chemo drugs, treatment and quality of life.  A visitor to the site can also add their own experience to the library, read patient diaries, exchange messages, and participate in chat rooms. ►

Young Adult Cancer Resource Site

Dedicated to 15-45 year-olds who have cancer. The mission of this site is to enable persons in this age group to benefit from the advances in cancer prevention, early detection, diagnosis and treatment that have been achieved in younger and older persons.   It assists persons to find the best available resources and clinical trials. ►

The Starbright Foundation

Dedicated to the creation and distribution of programs that empower seriously ill children and teens to address the challenges that accompany prolonged illness – and give them back their childhoods.  Programs include a private online community connecting over 30,000 kids living with chronic and serious illness. Kids can chat, email, read bulletin boards, find friends, learn about healthcare conditions, surf web sites and play games... all in a private and safe environment just for them. ► 

The Wellness Community

A national non-profit organization dedicated to providing free emotional support, education and hope for people with cancer and their loved ones. Through participation in professionally led support groups, educational workshops and mind/body programs utilizing the Patient Active Concept, people affected by cancer can learn vital skills to regain control, reduce feelings of isolation and restore hope—regardless of the stage of disease. With 20 facilities nationwide, The Virtual Wellness Community on the Internet and international centers in Tel Aviv and Tokyo, The Wellness Community provides a home-like setting for people living with cancer and their loved ones to connect with and learn from each other. All programs at The Wellness Community are free of charge. ►

Treatments for Ewing's Sarcoma

by Liddy Shriver and Bruce Shriver 

In this issue of ESUN, we will briefly discuss how clinical trials may fit into your treatment plan. 

First Line Treatments

The treatment for Ewing's sarcoma, like the disease itself, is aggressive.  The first line treatment is often 9-12 months long and can consist of 10-14 cycles of chemotherapy, resection surgery to remove the primary tumor, and radiation to the resection site.  The drugs used differ a bit depending on the specific protocol the doctor is following. Quite often the first line treatment consists of cycles of vincristine, Adriamycin, and cyclophosfamide alternated with cycles of etoposide and ifosfamide.  These and other chemotherapy agents will be discussed in the Drug News section of ESUN.  Baseline scans (e.g., CT, MRI, PET, and X-Rays) and baseline blood work is done at the beginning of the treatment regimen.   Additional blood work is done after each cycle or two in order to monitor the patient’s response to the chemotherapy agents and to see if the treatment should currently be continued (e.g., to see if your blood counts are high enough for you to continue with the drugs at the current time). 

Second Line Treatments

The response of your tumor to the chemotherapy might be able to be seen after 2-4 cycles of chemotherapy by scanning the primary tumor and other areas of your body and comparing the results to your baseline scans for primary tumor growth and for the development of metastatic sites (i.e., indications that your cancer is spreading to other sites). If the first line treatment isn't successful, the chemotherapy regimen is frequently changed to another protocol.  There is no particular regimen that all or most oncologists use for the second line treatment of Ewing’s sarcoma at this time.  A number of the alternative regimens have been shown to be equally as good as one another.  If your tumor appears to be stable (i.e., it responds to a chemotherapy regimen and your cancer has not spread), surgery may be considered for a second line treatment if it was not employed earlier.  If your tumor responds to a specific chemotherapy regimen but your cancer has metastasized, your oncologist might recommend that you have stem cells drawn to give you the option of using “high-dose” chemotherapy with stem cell transplant.  High dose chemotherapy with stem cell transplant is a very demanding but potential treatment to be considered for metastatic disease. 

Clinical Trials

If the cancer fails to respond to the first and second line treatments, you may turn to clinical trials.  A “clinical trial” is a well-planned research study that tests a drug or treatment method to see how well it works on people. In the US, clinical trials are overseen by the Food and Drug Administration.  They are typically carried out in a cancer clinic, institute, center, or other medical facility under the control of a medical team. Clinical trials involve rigorous testing, reporting and adherence to specific guidelines. Not all patients are eligible to be involved in a clinical trial, even if it includes the specific cancer they have.  There are constraints that might make you ineligible to participate in a specific clinical trial, e.g., your age, your previous chemotherapy regimens, and whether or not your cancer has metastasized.

What are the Different Phases of a Clinical Trial?

There can be up to four phases of a clinical trial. 

Phase I:  A Phase I Clinical Trial tests the safety, dosage levels, and response of a disease to a new drug or treatment method. Phase I Clinical Trials enroll a small number of patients, sometimes less than a dozen.   

Phase II:  A Phase II Clinical Trial tests if the new drug or method of treatment has an anti-cancer effect (e.g., if it shrinks a tumor, improves blood test results) and whether it works against one or more specific types of cancers.  

Phase III:  In a Phase III Clinical Trial, the results of people taking a new drug or using a new method are compared with results of people receiving an existing standard treatment.  The comparison might include, for example, which group has better survival rates or fewer side effects from the drug or treatment method. Drug and treatment method studies enter a Phase III Clinical Trial only if a drug or treatment method seems to work in Phase I and Phase II Clinical Trials. Phase III trials may include hundreds of people at many clinics and cancer centers nationwide.  

Phase IV:  This phase evaluates the side effects of a new drug or treatment method that were not apparent in the Phase III Clinical Trial once a treatment has been approved and is being marketed. This phase may involve thousands of people. 

Considering and Applying for Clinical Trials

There are a number of sources where you can learn of candidate clinical trials—e.g., from a member of your medical team, from the professional and lay literature, and from searching appropriate websites (see, e.g., the Clinical Trials section of the Links page on our website).  Clinical trials may involve a variety of different approaches in dealing with cancer; among them are using new drugs, new combinations of existing drugs, new protocols for administering drugs (e.g., different dosing and/or cycle lengths, i.e., “time compression” treatments), new combinations of chemotherapy and radiation therapy, and employing new methods for dealing with cancer (for example, investigating one of the two main immunotherapy approaches, antibody therapy and vaccine therapy). Once you have identified one or more candidate clinical trials—ones that deal with your cancer and for which you meet the eligibility requirements—we recommend that you do your research on the chemotherapy agents, protocols, and/or methods involved and then discuss them and the clinical trials with your oncologist. 

Suppose you are going to visit with the team conducting the clinical trial to see if you are a candidate for it. Here are some suggestions about what you should bring to your first appointment with the clinical trial doctors.

• Your medical history. The more of your medical history the doctor has, the “better” the appointment might go.  The medical history is used to determine if you can participate in the trial or not.  Details of the chemotherapy drugs that you have had (which drugs, their frequency, dosing, etc), pathology reports, CT scans, MRI scans, and X-Rays can often be very useful to aid the medical staff in making this determination.  Fill out as much of the paper work ahead as possible of time.  Have your insurance company approve your participation and provide the cancer center with the appropriate approval information before your visit.

• Your questions about the clinical trial itself.  What can you expect? What will be done, how often, when, and for how long?  Under what set of circumstances would you not be allowed to continue on the clinical trial after you have started it?  Since clinical trials involve the collection of research data for the oncologists and research staff, there are frequent blood tests (called "PK" studies, where PK = pharmacokinetic) which are collected over the first 2-3 cycles of the treatment.  These PK studies normally have to be done at the cancer center where the clinical trial is being conducted

• Your questions about the drugs that will be used, their frequency, dosing, side effects, precautions, known results, etc.

• Your questions about the tests you’ll need and where they can be done.  You may also have to undergo baseline and post treatment tests (e.g., CT scans, MRIs, PET scans, and/or X-Rays) as appropriate. These tests may or may not be able to be done elsewhere (e.g., near your home).  Where these tests are done may be a consideration if the site conducting the clinical trial is relatively far from your home.  You may need to plan to stay overnight near the cancer center depending on the location of the cancer center, how long the treatment takes, how long you are to be observed after the treatment, and when and where any after-treatment tests are scheduled. There are programs that might be able to help family with travel expenses associated with getting to and from cancer treatment centers.  Make sure when you call and make the appointment to get detailed directions to the cancer center facility, particularly if it is another city or state.

When considering if a clinical trial is “worth” your time (in contrast to only “aiding science” by your participation in it), you probably want answers to a number of questions. You can get help in obtaining answers to your questions and in understanding the issues involved from establishing a relationship with the Research Assistant or Research Nurse associated with the clinical trial. Remember to do your research before applying for a clinical trial.  Some sample questions for the Research Assistant or the Research Nurse are:

• Are there currently or have there been patients with my cancer on the trial?  Known results?

• Are there currently or have there been similar trials elsewhere in the US or abroad?  What was learned about dosing and types of cancer the drugs have been successful with in these trials?

• Is this a multi-center trial?  Are there any results known from using the drugs in other centers?

• Has the protocol been used on a “compassionate use” basis? Compassionate use is discussed below.

Making Your Decision

Beyond Clinical Trials

Even if you can participate in a clinical trial, it might not be your best course of action.  For example, participation at the beginning of a Phase I trial where the amount of chemotherapy received is very small, might have the effect of reducing your eligibility to be considered as a candidate in a future clinical trial.  If a Phase I trial is the only current clinical trial option, it might be better to wait for another trial, or to try a chemotherapy agent off-study or in a “compassionate use” context.  After a successful clinical trial, the FDA approves a drug for use for one or more cancers.  “Off-study” refers to using an FDA approved drug for a cancer other than those for which it was approved. A patient with advanced disease or with no approved treatment or clinical trial options can attempt to get access to a new, unapproved drug outside of participating in a clinical trial.  Access to a drug outside of a clinical trial prior to FDA approval is commonly referred to as “compassionate use”.  We will discuss compassionate use in more depth in one of our upcoming issues. 

Useful link: The Cure Our Children Foundation’s new drugs, therapies and clinical trials page.   ►

SFA Grant Application Review Underway

by Dr. Mark Thornton

As part of its mission, the Sarcoma Foundation of America (SFA) provides "Starter Grants" to investigators interested in basic science sarcoma research. This SFA program is meant to encourage research involving the development of novel agents against sarcoma or research that could potentially lead to the development of novel agents against sarcoma.  In accordance with IRS instructions, SFA grants cannot fund clinical trials, but all other areas of research can be considered for funding.  Generally, the award will be approximately $25,000.  The deadline for applying for 2004 funding recently passed, with the SFA receiving eight applications from outstanding sarcoma researchers from around the country.  If your oncology team did not submit a grant proposal this year, perhaps it may be interested in applying next year.  For more information, click here. The Initiative raised over $75,000 for SFA in 2003 to help fund these grants. ►

Odds and Ends

Prognostic Factors for Sarcomas

Paul Meyers of Memorial Sloan Kettering Cancer Center defines the prognosis for a patient as the “probability of survival or event-free survival at a specified interval from diagnosis”. In his short 3-page editorial in the February 2003 issue of the Journal of Clinical Oncology, he discusses 3 reasons why oncologists study prognostic factors: (1) to counsel patients and their families about their prognosis “so that they can make informed choices about treatment”; (2) if the estimates of probability are sufficiently robust, “they may allow us [i.e., oncologists] to assign patients to different treatments”; and (3) the identification of factors that predict outcomes “may lead to identification of novel targets for therapy”.  See Prognostic Factors for Sarcomas: Hard and Soft, by Paul Meyers, Journal of Clinical Oncology, Vol. 20, Issue 3 (February), 2002: pages 627-629. ►

Cure: Cancer Updates, Research & Education

The Winter Issue 2003 (Vol. 2, No. 4) of Cure magazine contains, among many other interesting things, an informative article titled, "Bexxar: Birth of a Drug" which describes the long and winding road to getting a new chemotherapy agent approved by the FDA. Cure can be found online by clicking here. ►

Research Corner

by Bruce Shriver

In each issue of ESUN, this column will take note of interesting research results indicative of the wide range or work in sarcoma related research. Please send me references to material that you'd like to bring to the attention of our readership by clicking here.

Telomerase activity and outcome in patients with nonmetastatic Ewing family of tumors

A “marker” is a diagnostic indication that disease may develop. Telomerase is an enzyme composed of RNA and protein. It is present in cells that are rapidly dividing, e.g., in embryos and tumors.  So, telomerase is considered a molecular marker for malignancy. Mr. Ohalai and his colleagues present the results of a study in which they attempt to determine “telomerase activity (TA) as a prognostic factor at diagnosis and as a marker for minimal residual disease during therapy and follow-up in nonmetastatic Ewing family of tumors (EFT)”.  They conclude that the results of their study “suggest that TA is a significant prognostic variable, superior to the established clinical prognostic parameters during therapy and tumor surveillance. It could be used in combination with RT-PCR for a new risk classification”.  See Association between telomerase activity and outcome in patients with nonmetastatic Ewing family of tumors, by Ohali A, Avigad S, Cohen IJ, Meller I, Kollender Y, Issakov J, Gelernter I, Goshen Y, Yaniv I, and Zaizov R., Journal of Clinical Oncology. October 15, 2003, Vol. 21, Issue. 20, pages 3836-43. ►

High-dose therapy for patients with primary multifocal and early relapsed Ewing's tumors

Mr. Burdach and his colleagues point out that “Patients with bone or bone marrow metastases or early or multiple relapses constitute the worst risk group in ET and have a poorer prognosis than patients with primary lung metastases or late relapses”. They compare the results of the Meta European Intergroup Cooperative Ewing Sarcoma Study (MetaEICESS) with the result of the previous Meta European Intergroup Cooperative Ewing Sarcoma Study (hyperME]).  They conclude that, “TandemME offers a decent, albeit still not satisfactory, rate of long-term remissions in most advanced ETs (AETs), with short-term treatment and acceptable toxicity. … Future prospective studies in unselected patients are warranted to evaluate high-dose therapy in an unselected group of patients with AET”. See High-dose therapy for patients with primary multifocal and early relapsed Ewing's tumors: results of two consecutive regimens assessing the role of total-body irradiation, by S. Burdach, A.. Meyer-Bahlburg A, H. J. Laws, Haase R, van Kaik B, Metzner B, Wawer A, Finke R, Gobel U, Haerting J, Pape H, Gadner H, Dunst J, and Juergens H., Journal of Clinical Oncology, August 15, 2003, Vol. 21, Issue 16, pages 3072-8. ►

Long-Term Event-Free Survival After Intensive Chemotherapy for Ewing’s Family of Tumors in Children and Young Adults

Mr. Kolb and his colleagues report on their effort to “improve the long-term event-free survival of patients with Ewing’s family of tumors (EFTs) using high-dose, short-term chemotherapy”. In their study, “Patients received seven cycles of chemotherapy. Cycles 1, 2, 3, and 6 consisted of cyclophosphamide 2,100 mg/m²/d on days 1 and 2, and a 72-hour continuous infusion of doxorubicin 75 mg/m² and vincristine 2 mg/m² starting day 1. Cycles 4, 5, and 7 consisted of 5 consecutive days of ifosfamide 1,800 mg/m²/d and etoposide 100 mg/m²/d”.  They concluded that, “Sustained EFS [i.e., event free survival] and OS [i.e., overall survival] can be achieved with intensive chemotherapy in children and young adults with local-regional EFTs”. However, they note that, “This therapy is relatively ineffective in the treatment of metastatic EFTs”.  See Long-Term Event-Free Survival After Intensive Chemotherapy for Ewing’s Family of Tumors in Children and Young Adults, by E. A. Kolb, B. Kushner, R. Gorlick, C. Laverdiere, J. Healey, M. LaQuaglia, A. Huvos, J. Qin, H. Vu, L. Wexler, S. Wolden, and P. Meyers, Journal of Clinical Oncology, Vol. 21, Issue 18, September 2003, pages 3423-343. ►

The Impact of the Internet on Cancer Outcomes

In this article which appears in the Lippincott, Williams & Wilkins publication "CA—A Cancer Journal for Clinicians", Dr. Eysenbach identifies four areas of Internet use: "communication (electronic mail), community (virtual support groups), content (health information on the World Wide Web), and e-commerce". He provides a "conceptual framework summarizing the factors involved in a possible link between Internet use and cancer outcomes".  You can download the article in PDF format free at the CA website. ►

Recent and Upcoming Meetings Relevant to Sarcoma-related Reseach

November 6-8, 2003, 9th Annual Connective Tissue Oncology Society (CTOS) Meeting. ►

Journals and Magazines

Each month we will give an overview of one of the journals or magazines that have articles dealing with sarcoma.  From time to time you might read an article in one of these publications that you would like to bring to the attention of your medical team and have them explain its relevance to your own situation. This month we examine the Taylor & Francis Publication, Sarcoma.

Sarcoma is a quarterly publication that publishes papers covering all aspects of connective tissue oncology research. Sarcoma brings together “work from scientists and clinicians carrying out a broad range of research in this field, including the basic sciences, molecular biology and pathology and the clinical sciences of epidemiology, surgery, radiotherapy and chemotherapy”. The research that is reported on covers “the entire range of bone and soft tissue sarcomas in both adults and children, including Kaposi's sarcoma, are published as well as preclinical and animal studies”.  Articles in Sarcoma describe “advances in diagnosis, assessment and treatment of this rarely seen, but often mismanaged, group of patients. It is of interest to all those working with bone and soft tissue tumors, including medical, surgical and pediatric oncologists, radiotherapists, pathologists and research scientists”. ►

Clinical Trial News

Vincristine, Doxorubicin, Cyclophosphamide and Dexrazoxane (VACdxr) With or Without ImmTher for Newly Diagnosed High Risk Ewing's Sarcoma. This Phase II study,  sponsored by M. D. Anderson Cancer Center, is currently recruiting patients.  For more information, click here.

Studying Genetic Changes in Ewing's Sarcoma Tumors. This study, sponsored by the National Cancer Institute, is currently recruiting patients. The purpose of this study is to maintain a tissue bank from tumor biopsies donated by patients with Ewing's sarcoma to learn about genetic changes seen in these tumors. Researchers use tissue samples of Ewing's sarcoma tumors to conduct research with the goal of improving the treatments for this disease.

Comparison of Filgrastim and Filgrastim SD/01in Boosting White Cell Counts after Intensive Chemotherapy.  This Phase I study, sponsored by the National Cancer Institute (NCI), is currently recruiting patients.  The purpose of this randomized open label trial is “to compare the tolerance, toxicity, and therapeutic effects of Filgrastim-SD/01 given as a single injection after chemotherapy to daily subcutaneous filgrastim in patients with newly diagnosed sarcoma. The pharmacokinetics of Filgrastim-SD/01 will also be compared to the pharmacokinetics of filgrastim. This trial will also be a platform for performing biological studies of these tumors and for detailed cardiac studies. High-risk patients who are treated on this front line trial and respond will also be candidates for a planned transplant protocol. A total of 34 patients (17 patients per treatment arm) will be entered onto the trial”.

Our Initiatives

We encourage you to visit The Initiative's website. Part of it is devoted to our various initiatives, some of which are listed below.  We encourage you to become involved in them.

Our Journeys Page

We publish stories, essays, poems and other expressions by patients, caregivers, friends, and medical staff who have had to live with cancer.  Knowing others are experiencing some of what we personally are going through can be of great help in confronting cancer.

2004 Cycle Zydeco Ride

We had intended to ride in the 2004 Cycle Zydeco bike tour as we did last year.  Cycle Zydeco is an annual Cajun/Creole Food Cycling Festival where you can enjoy the food, music, and people that have made this part of South Louisiana internationally famous.  It is steeped in the culture and heritage of French-speaking Cajuns and the Creoles. You can ride at a leisurely to moderate pace so you can take in the countryside.  In the evening you can relax, enjoy great food, and dance to Cajun and Zydeco music.  Unfortunately, we could not make the arrangements to do so this year.  However, a number of riders in Cycle Zydeco 2004 will be biking as a memorial to Liddy and wearing Team Sarcoma armbands, helping to spread the awareness of sarcoma.

2003 Shriver Family Bike Tour for Sarcoma Research

During early July 2003, 28 members of Team Sarcoma took to the bike paths and back roads of Denmark.  They were joined by 260 Virtual Bike Tour riders from around the world.  Read about this amazing event, which raised over $75,000 for the Sarcoma Foundation of America, by clicking on the above link. 

2003 Cycle Zydeco Ride

This was the very first initiative Team Sarcoma undertook.  In  April 2003, eight of us took to the back roads of south central Louisiana.  We raised over $14,000 for sarcoma research at Columbia University.  Read about this inaugural event by clicking on the above link.

May 2004 Silent Auction

We're planning a silent auction in May 2004.  More details on this will be provided as the plans become more definite. ►

Q and A

Q: What is angiogenesis and how does it play a role in cancer treatment?

A: by Dr. Mary Louise Keohan

Blood vessels are the tubes through which the blood circulates in the body. They include an interconnected network of arteries, arterioles, capillaries, venules, and veins. Angiogenesis (an-gee-o-gen-eh-sis) is a multistep biological process that stimulates the development of new blood vessels and tumor metastases while maintaining existing blood vessels.  Endogenous positive and negative regulating factors control the process. “Endogenous” refers to something produced inside an organism or cell; whereas as "exogenous" is the opposite, i.e., produced external to the organism or cell.

Tumor angiogenesis is the growth of blood vessels between a tumor and its surrounding tissue. New blood vessels help the tumor to grow by feeding the cancer cells with essential nutrients and oxygen.  Anti-angiogenesis agents or “inhibitors” are substances which prevent or destabilize the angiogenic process in a number of different ways (e.g., inhibition of endothelial cell growth and migration, suppression of the synthesis and degradation of the vessel basement membrane and extracellular matrix and blockage of angiogenic factors).  There are many anti-angiogenesis agents in development and a number of agents currently being evaluated in clinical trials. Many have unique ways in which they perform their anti-angiogenic function. 

Angiostatin is a piece (a fragment) of a protein, plasminogen, which plays a role in blood clotting. Angiostatin is normally secreted by tumors (at least in laboratory mice) and appears to halt the process of developing new blood vessels which is necessary to tumor development. It is hoped that Angiostatin may be used to develop a new class of anti-angiogenesis agents.

Endostatin is a piece (a fragment) of a protein, collagen 18, which appears in all blood vessels. Endostatin is normally secreted by tumors (at least in laboratory mice) and appears to halt the process of developing new blood vessels which is necessary to tumor development. It is hoped that Endostatin may be used to develop a new class of anti-angiogenesis agents.

Vascular Endothelial Growth Factor (VEGF) is a protein involved in the process that stimulates angiogenesis by binding to specific receptors on nearby blood vessels to grow extensions to existing blood vessels.  An increased amount of VEGF in the bloodstream has been correlated with a poor prognosis in some tumor types. To date there are no surrogate markers for evaluating angiogenesis inhibitor efficacy.  A monoclonal antibody, called rhuMab VEGF, has been developed that is designed to bind to VEGF and thus preventing the VEGF from binding to the receptors on the nearby blood vessels.  It is hoped that this will prevent tumor growth. Bevacizumab (a.k.a. Avastin) is also a VEGF-based inhibitor.

Thrombospondin is one of a family of glycoproteins that are made in cells, secreted by cells, and incorporated into cells including blood platelets. The thrombospondins are known to interact with blood coagulation and anticoagulant factors. They are involved in cell adhesion, platelet aggregation (clumping), cell proliferation (growth), angiogenesis (blood vessel formation), tumor metastasis, and tissue repair. Thrombospondin-1 and thrombospondin-2 have been shown to be potent inhibitors of angiogenesis and suppressors of tumor growth in laboratory mice.

Matrix metalloproteinase is a member of a group of enzymes that can break down proteins that are normally found in the spaces between cells in tissues. These enzymes need zinc or calcium to work properly. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. Several matrix metalloproteinase inhibitors are being studied; among them is BMS-275291.  

Click here to link to “Angiogenesis and Cancer Control: From Concept to Therapeutic Trial” by Dr. Steven Brem.

Click here to link to a listing of some of the current angiogenesis inhibitors clinical trials

Send your questions to us.  If we can, we'll reply to them either in ESUN or by personal e-mail. ►

Drug News

by Dr. Karen Albritton

Chemotherapy (also know as “chemo”) is the treatment of cancer with drugs that can destroy cancer cells. There are a wide variety of drugs used in the treatment of sarcoma. In each issue of ESUN, this column will briefly examine an existing or a new chemotherapy agent that is currently used for or is in a clinical trial for treating sarcoma.  In this issue, we’ll look at vincristine.  As mentioned in the Treatments for Ewing’s Sarcoma section of this e-Newsletter, the first line treatment for non-metastatic Ewing’s sarcoma often consists of cycles of vincristine, adriamycin, and cyclophosfamide alternated with cycles of etoposide and ifosfamide.  

Vincristine is a “mitotic inhibitor”.  Mitosis is the process of cell division in which each new cell receives the same amount of DNA as the parent cell. Drugs that block this process are called “mitotic inhibitors” or “antimitotic drugs”. Vincristine and other chemotherapeutic agents are given through a small piece of tubing inserted into the patient’s vein either in a peripheral vein (e.g., a temporary IV in the arm) or a central vein via a Hickman catheter, Broviac catheter, or a port-a-cath (also known as a “port”).  A port is a device surgically inserted under the skin into a large vein in the chest for long-term use to administer drugs and nutrients and to take blood samples.

Vincristine is a clear solution (i.e., it looks like water) that is injected into the patient over 2 to 5 minutes.  Because vincristine is a vesicant (meaning it can cause severe tissue damage if it leaks out of the vein) if given in a peripheral vein, it must be given carefully by trained nurses.  Vincristine can be given by itself on an out-patient basis; however, some centers suggest hospital admission when it is given with cyclophosfamide and doxorubicin.  The most common dose is 2mg/m² up to a maximum dose of 2 mg.  The specific amount given is usually based on a patient's height and weight.

Vincristine has no immediate toxicities but can cause jaw pain, constipation, foot or leg numbness, pain or weakness (i.e., neuropathy). The pain is treated with Tylenol or stronger pain medicine.  The constipation is treated with stool softeners or laxatives. The extremity neuropathy sometimes requires holding or reducing doses of the drug.  Rarer side effects are mild suppression of blood counts, hair loss or seizures.  There is not a maximum number of times that vincristine can be given to an individual, but too many doses over a given interval (such as when given weekly for more than 6 to 8 weeks) is likely to cause the side effects mentioned above, requiring “time-off” the vincristine. You can find an informative tutorial on chemotherapy and other treatment procedures at the MEDLINEplus Interactive Health Tutorials website.  ►