NEWSLETTER
Vol.6 No.1 An RRP Foundation Publication 1997
Spring
P.O Box 6643, Lawrenceville, NJ 08648-0643
_________________________________________________________________________________________________________
!!!!!!!!!!!! New RRPF Phone Number !!!!!!!!!!!!!
The main RRPF phone number is
now:
(609) 530-1443
!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
Contents
· Opening comments - p. 1
· RRPF organizational information - p. 2
· New
RRPF Scientific Advisor - p. 2
· RRP Remission
and Network
News - p. 2-3
· RRP
National Issues - p. 3-4
· Patient
Statistics - p. 4
· Update
on Adjunct Therapies and new protocols -
p. 5-6
indole-3-carbinol
- p. 5-6
Mumps vaccine and
RRP - p. 6
PDT at LIJ
- p. 6-7
· Research
Activities Update - p. 6-8
Research Update from Univ. of Iowa - p.
6-7
Research Update from Univ. of Alabama -
p.7
Diet Based Studies and HPV - p. 7
Vaccines for
HPV - p. 7-8
· Patient
profile - p. 8
· RRPF Mission Statement, Information/Support
Centers, subscription form - enclosure
From the Editor
My apologies for the delay in completing this newsletter issue. The Stern family is finally getting settled into our new home after a very lengthy and time consuming construction process which was diverting much of our attention away from other activities.
The RRP Newsletter is vital to our support
services and networking efforts. As always we welcome your comments
and suggestions to help us improve this publication. We continue
to seek people from the RRP community to actively participate in the
RRPF and the RRP Newsletter. This includes practitioners,
researchers, patients and families. If you have any interest in this
regard, please contact any of the directors or officers (see page 2
for addresses). Additional help is needed to continue and build on
the efforts of the RRPF. Once again we appeal for your
assistance. Specifically:
1) We are looking for people who are willing to
serve as editors for the RRP Newsletter on a regular
basis. In addition I invite more people to help us gather information
and write articles.
2) Because of the continued growth of the RRPF, we
recently found it necessary to employ the services of a local
database expert on an as needed basis to coordinate and redesign some
of our databases, but we are still looking for volunteers to help us
maintain and expand our data gathering efforts.
Our thanks to all those who have responded to our appeal for help. If you would like to help in any way, don't hesitate to contact me at the address listed on page 2.
Thank you.
Bill Stern
We are most grateful to all those individuals, medical professionals and corporations who have supported the RRPF. In this regard we would like to take this opportunity to acknowledge a special contribution from the Fidelity Investments Charitable Gift Fund sponsored by Wan and Cecilia Lo. Although it is impossible to publish the names of all who contribute, we extend our sincere thanks to everyone who has supported our efforts.
Future donations from individuals, professionals or from the business community will be very much appreciated. Tax deductible contributions may be made to:
RRP Foundation
P.O. Box 6643
Lawrenceville, NJ 08648-0643
Do you donate to the United Way through your employer? You can select a "Donor Choice" option which would allow you to direct a donation to the RRPF as the 501 (c) (3) of your choice.
We would like to take this opportunity to acknowledge donations received from the following local United Way chapters during the past year: San Diego County, CA., Washington, DC. and Mercer County, NJ. Also we have been contacted by chapters from Southeastern PA and Oregon in anticipation of receiving donations from them. We thank all those individuals who contributed in this way. Your help is very much appreciated.
A final note on the subject of donations which Jeff
Newman, who has been a member of our network for more than 4 years,
has asked us to pass along. When Jeff is asked by someone he knows to
support their cause he always asks that person to reciprocate by
supporting the RRPF. We very much appreciate any and all fundraising
efforts on behalf of the RRPF, but we also do not want members of the
support network to feel any obligation in this regard.
To physicians and nurses: Please distribute
copies of this newsletter to your RRP patients.
If you are not registered with the RRPF, please do
so by completing the Practitioner Questionnaire
enclosed.
RRPF Officers, Directors & Advisors
Marlene Stern
President
P.O. Box 6643
Lawrenceville, NJ 08648-0643
(609) 530-1443
mstern@pucc.princeton.edu
Bill Stern
Treasurer and Director
P.O. Box 6643
Lawrenceville, NJ 08648-0643
(609) 530-1443
wfs@gfdl.gov
Henry Woo, Esq.
Secretary
1700 17th Street, NW., Suite 405
Washington, DC. 20009
henrywoo@erols.com
Diane Burke, RN
Director
Department of Otolaryngology
The Univ. of Iowa Hospitals and Clinics
E230 GH, 200 Hawkins Drive
Iowa City, IA 52242
(319)356-1765
diane-burke@uiowa.edu
Susan Woo
Director
7107 Georgia St.
Chevy Chase, MD 20815
(301)652-6826
[Please see the enclosure for a complete list of the RRPF regional and state coordinators]
Scientific Advisory Committee
Thomas R. Broker, PhD, University of Alabama at Birmingham Schools of Medicine & Dentistry
Haskins K. Kashima, MD, Johns Hopkins University School of Medicine
Linda Miller, RN, MSN, Children's Hospital of Philadelphia
Robert J. Ruben, MD, Albert Einstein College of Medicine
Keerti V. Shah, MD, DrPH, Johns Hopkins University School of Hygiene and Public Health
Bettie M. Steinberg, PhD, Long Island Jewish Medical Center
Kathleen Sullivan, RN, Children's Hospital of Boston
The RRPF would like to welcome Prof. Keerti V. Shah, MD.., Dr. P.H., HPV/RRP researcher, to our committee of scientific advisors.
Dr. Keerti Shah is a physician-virologist with a strong interest in epidemiology and natural history questions. He is a professor at the Johns Hopkins School of Hygiene and Public Health and has worked on RRP since 1980, most often in collaboration with Drs. Haskins Kashima and Pheobe Mounts. His work has produced numerous publications involving RRP including several landmark works dealing with issues of transmission and risk factors.
RRPF Publication and Subscription Policy
The RRPF produces two publications semi-annually, the RRP Newsletter and the RRP medical reference service. The RRP Newsletter focuses mainly on the human and clinical aspects of recurrent respiratory papillomatosis and in this regard targets a broad readership, including patients/families, attending physicians/nurses, as well as researchers and the general public seeking to stay in touch with RRP from a clinical perspective. The RRP medical reference service serves those in the community seeking a more comprehensive understanding of this disease. Please help us by supporting these publications and other RRP services including patient outreach, support and advocacy.
Subscription Policy and Minimum Annual
Donations
RRP Newsletter
Professional/Corporate - $25
Individual - $15
RRP Newsletter plus Medical Reference Service
Professional/Corporate - $40
Individual - $25
(see RRPF subscription form enclosed)
[Note: Back issues of the RRP Newsletter and Medical Reference Service ($10/issue) are available upon request, subject to availability]
by Judy Thompson and Bill Stern
These very brief patient profiles are intended to let you know that some of those with RRP are doing quite well.
Anthony from Kentucky, now nine years old, has been disease free for nearly a year and a half. It was about that time that he started taking acyclovir. Before then he had been having regular laser surgeries at 2-3 month intervals.
Four year old Trey from Maryland has had 14 laser surgeries. In March of 1996 he started drinking cabbage juice regularly and shortly thereafter a dramatic improvement was seen. He was examined in December 1996 and just recently again in April 1997 with no sign of papillomas and a strong voice.
Scott from Iowa is now 5 years old with a strong voice and has not had a need for surgery since February of 1996. Before that time he was averaging about 5 surgeries a year. He did take I3C for about a year starting in June of 1996.
Others still in remission include: Ariel from
California, now
5 1/2 years old; Steph from Florida, age 23; Jeff
from Illinois, age 49; Emily from Michigan, now almost 9; Leah from
New Hampshire age 17; Lindsay from New Jersey, now 7 1/2 years old;
Melissa from New York, who is almost 8; Kaitlyn from Tennessee now
more than 4 1/2 ; Smokey from Virginia, age 25; Rita from
Pennsylvania, now 3 years old; Jim from North Dakota, at age 44 and
Ralph from Pennsylvania, now age 70.
If you feel that you or your family member is in remission and would like to share this information with the RRP community, please contact:
Judy Thompson
3184 Eutaw Forest Dr.
Waldorf, MD 20603 (301) 843-6378
email: jthompson@gpo.gov
Our international support network has grown to over 350 respiratory papilloma families. Patients range in age from 1 to 81 years and are located in 41 states, the District of Columbia, three Canadian provinces, the United Kingdom, Spain, Macedonia, Croatia and Morocco.
Since its introduction in revised form with the Spring 1996 issue, we have received patient/therapy questionnaires from approximately 100 families in the support group. Our thanks to all who have taken the time to fill out this questionnaire. Please note that we have further revised the structure of the questionnaire (which will hopefully make it easier to complete). If you haven't completed a questionnaire in the past, please take a few minutes to fill out the forms enclosed. If you have previously filled out a questionnaire, you need only identify yourself, mark UPDATE along the top front of the form and answer only those questions where you have new or updated information to provide. Please note that we are requesting the information contained in this survey be made available for RRP research; in this regard there is a place in the survey to grant permission. Please return the surveys to Marlene and Bill Stern. In addition, RRP families, please review the Patient Directory listings and notify us regarding any corrections, omissions or additions. If you are not included in the directory and would like to be, please notify Bill or Marlene Stern.
Communication and information exchange throughout the support group and the RRP community remains a primary focus of the foundation. The RRPF maintains an account with America-On-Line (AOL) and can arrange for you to have a limited amount of free time on AOL for RRP related communications; just get in touch with Bill Stern. The RRPF maintains a page on the World Wide Web (WWW); the address is (http://members.aol.com/rrpf/RRPF.html) . Our page is cross linked with other WWW home pages that we feel are relevant to the RRP community. In the future we are proposing to include a directory of internet addresses (and WWW home page sites) for RRP patients/families, doctors, researchers and others with an interest in RRP. Please let us know if you would like to be included.
.....................................................................................
American Academy of Otolaryngology
The RRPF maintained a booth the 1996 AAO-HNS meeting in Washington, DC. In attendance were Marlene and Bill Stern (RRP parents, RRPF officers) and Lindsay Stern (RRP patient); Beverly Brody (RRP mother); Jamie Johnson Smalls (RRP grandmother) and Antonio Johnson (RRP patient); Diane Burke (RRP nurse, RRPF officer); Susan Woo (RRP mother, RRPF officer); Bill Lazar (RRP grandfather, ALPF President) and Nelson Delgado (ALPF Secretary). Pictured below are a few of the attendees (from left to right: Marlene Stern, Lindsay Stern, Antonio Johnson, Jamie Johnson Smalls and Beverly Brody).
by
Lori Armstrong, Ph.D.*
On January 16, 1997 the Centers for Disease Control and Prevention (CDC) hosted a training meeting for the site coordinators of the RRP Registry. Representatives consisting of otolaryngology nurses and doctors, and data managers, from all 22 registry sites around the United States, attended a one-day seminar to become familiar with the protocol and medical chart abstraction form. The chart abstraction form is the main data-gathering tool for the registry. (It provides a format for collecting information from a patient's medical record regarding demographics, date of surgeries, sites of papilloma and some other limited clinical information.) The registry will collect demographic, surgical and drug treatment information, and other medical data on children with RRP aged 17 years and younger. Children with current active disease will be included and followed for three years. All the data will be gathered from the child's medical record; there are no plans to do parent interviews at this time. Parent interviews will likely come with the design of a case-control study to look at the risk of HPV infection, HPV transmission, and severe or recurrent disease in children with RRP. Currently, site coordinators can include RRP patients over 17 years old optionally, as their time and resources permit. Any changes in the registry protocol, such as formally including adult patients or to gather other medical information, will be addressed after we successfully gather and analyze the data under the current registry protocol. I am looking forward to continued collaboration with the registry site coordinators and principal investigators who work diligently to make the RRP registry a success.
* Division of Viral and Rickettsial Diseases,
Centers for Disease Control and Prevention
Mail Stop G-18, 1600 Clifton Road, NE..
Atlanta, GA 30333
.......................................................................................
[ Editorial Comment: The RRPF is pleased that progress is being made by the Centers for Disease Control and Prevention toward establishing a national registry of RRP patients. We hope that limiting data collection to patients aged 17 and younger and those who are currently active (i.e., at least one surgery in the last 3 years) are only temporary constraints due to funding considerations. We feel that a true national registry should attempt to include all patients for whom records can be obtained. A major goal of the RRP national registry should be to provide a comprehensive epidemiological database which will be accessible to both RRP researchers and practitioners and thereby further their ability to better understand and treat this disease.]
A successful RRP registry will require continued funding. In addition, a number of proposed scientific and clinical studies involving promising therapies for the treatment of RRP are in need of funding. Government agencies are a very significant source of support for these RRP research efforts. In this regard we continue to urge you to contact your congressional representatives and senators to make them aware of RRP and mobilize their support. Regarding funding of a National Registry for RRP, ask them to contact :
The director of the National Center for Infectious Diseases:
James Hughes, MD, Director
National Center for Infectious Diseases
Centers for Disease Control
Atlanta, GA 30333
Others for representatives & senators to contact:
The contract officer at NIH.:
Dr. Penelope S. Hitchcock
Chief, Division of Microbiology & Infectious
diseases
National Institute for Allergy & Infectious
diseases
Solar Bldg., Rm. 3A24
6003 Executive Boulevard
Bethesda MD 20892-7630
Phone: (301) 402-0443; Fax: (301) 402-1456
The director of the FDA:
David A. Kessler, MD
Commissioner of Food & Drugs
Food & Drug Administration
Park Lawn Bldg., Room 1471
5600 Fishers Lane
Rockville, MD 20857
Director of Nat. Inst. for Allergy &
Infectious diseases:
Anthony Fauci, MD
Assistant Secretary for Health:
Philip Lee, MD
The statistics that follow are based on RRPF questionnaire responses. There has been no attempt to determine statistical significance, so caution is urged in drawing conclusions from the numbers below.
In addition to these data, results regarding adjuvant therapies are presented on page 5.
Tables 1 - 3 provide a breakdown of the patients in the support group based on sex and age; the sample sizes for tables 1-3 range from 297 to 320.
Table 1. Total number of patients in support group reporting
Females - 147
Males - 173
Table 2. Distribution of patients based on current age brackets and sex
Under 10 - Females = 72, males = 57, Total =
129
10-20 - Females = 25, males = 28, Total =
53
20-30 - Females = 11, males = 13, Total =
24
30-40 - Females = 12, males = 14, Total =
26
40-50 - Females = 12, males = 25, Total =
37
Over 50 - Females = 9, males = 19, Total =
28
Table 3. Distribution of patients based on diagnosis age brackets and sex
Under 10 - Females = 110, males = 91, Total =
201
10-20 - Females = 5, males = 3, Total = 8
20-30 - Females = 15, males = 14, Total =
29
30-40 - Females = 3, males = 19, Total =
22
40-50 - Females = 7, males = 20, Total =
27
Over 50 - Females = 3, males = 8, Total =
11
Table 4. Distribution of respiratory papilloma sites of involvement based on responses from 92 patients
above cords - 48
at cords - 92
below cords - 35
tracheal - 21
bronchial - 6
lung - 5
Table 5. Birth Statistics from Patient Support Network*:
* More details will be published in a proposed journal article with researchers from Johns Hopkins.
Adjunct Therapy and Protocol Update
The following reports of statistics and clinical research involving RRP therapies, represents a best effort to make an accurate and objective presentation of information from surveys, articles submitted by investigators, personal communications and reference to literature. Where appropriate the RRPF has provided its input in a constructive manner which we hope will best serve the RRP community.
by Bill Stern
Adjunct therapy survey responses from 228 patients/families have been received. Of those responding 85 indicated that they have not used any adjunct therapies and 143 responded that they have tried adjunct treatments (many have tried more than one). The most reported therapy was indole-3-carbinol (I3C) with 89 users and next was interferon (IFN) with 55 users responding. The patient/parent assessed impact of some adjuvant therapies is summarized in the table below. In this table the sample sizes include only the subset of adjunct therapy users who indicated some response to a treatment, either some improvement (Improve) or no impact (None). If some improvement is noted, it is further broken down into either a complete response (Comp, i.e., no new growths seen at two typical surgical intervals) or a partial response (Partial).
Table 1. Patient/family assessed impact of adjuvant therapies reported
I3C
IFN
Acyc
PDT
Ribvrn
Retin
Mumps
Others
Some notes regarding the above table:
The therapies are abbreviated as follows, I3C = indole-3-carbinol, IFN = interferon, Acyc = acyclovir, PDT = photo dynamic therapy (using Photofrin), Ribvrn = ribavirin, Retin = retinoic acid or accutane, Mumps = mumps vaccine (more details on page 6). In the category of other therapies used, improvement has been noted using the following treatments: Thuja (a homeopathic anti-viral), a mixture of vitamins including vitamin C and vitamin A, ShapeRite immune formula (see page 6 for more info.), topical 5-flourouracil (5FU), bleomycin and cobalt.
As indicated in previous RRP Newsletter issues, there was significant variation in dosages, brands and types of IFN used. (Most clinical trials have been with interferon-alpha. Additional controlled studies of interferon-beta, interferon-gamma and imiquimod, an inducer of interferons, are still needed.) Almost all IFN users reported some side effects, with a low grade fever being the most common complaint, and headaches, nausea and fatigue also being reported. I3C does not generally produce any obvious side effects, although there was one report of some minor stomach upset upon starting the therapy and two reports of temporary dizziness when a significant overdose was consumed.
Finally, we continue to remind our readers that these results are based on patient perspectives. Although the survey encourages objectivity and quantitative assessment as much as possible, these analyses cannot replace well designed clinical trials and research. We do hope that this information can provide guidance for those patients seeking adjunct therapies as well as those pursuing RRP related research.
.............................................................................
by Bill Stern
For background information about the impact of indole-3-carbinol (I3C) on estrogen metabolism and how this subsequently may act to reduce the growth rate of respiratory papillomas, see the RRP Newsletters Fall 93 through Fall 94 as well as Bradlow et al., 1996, J. of Endocrinology 150, S259-S265; Newfield et al.., 1993, Anticancer Research 13,337-342
If you are interested in obtaining more information about clinical trials involving I3C, please get in touch with one of the principal investigators as follows:
University of Pittsburgh:
Clark A. Rosen, MD. - (412) 647-2112
University of Tennessee:
Gayle E. Woodson, MD. - (901) 448-7677
Jerome Thompson, MD. - (901) 572-4400
The RRPF continues to encourage research studies involving I3C as an RRP adjunct therapy. In this regard we suggest that those patients who are interested in I3C as an adjunct treatment for RRP become part of a clinical trial. For those who are unable to participate in an I3C trial, but who would like to pursue this therapy on their own, we have been providing information regarding how and where to get I3C and how much to take. In addition, we continue to supply urine analysis testing information and supplies to RRP patients upon request. Thus far we have had requests for and have mailed out approximately 65 test kits. Along with the kits detailed instructions are included for collecting urine samples and sending them to Strang Cancer Prevention Center for analysis. In this regard we ask for your patience. These analyses are being performed as part of a research program by a limited number of scientists who depend on various funding sources to cover laboratory expenses. The RRPF will continue to assist their efforts.
How to get I3C and How much to
take
I3C may now be purchased from:
THERANATURALS Inc.
PO. Box 344
Orem UT 84059-0344
(801)224-8893 - Telephone and Fax
[They are able to take credit card orders by
phone]
Theranaturals is selling I3C in capsule
form, each capsule will be guaranteed to contain 100 milligrams of
I3C*. Each bottle will contain 100 capsules.
Pricing (which includes surface UPS shipping) :
$35.00 for one bottle; $95.00 for a package of 3
bottles
add $10.00 to above prices for Fed X
shipping.
Approximate dosing information is
based on preliminary results of Dr. Leon Bradlow's estrogen
metabolism studies, as follows:
Estimated dosages - Adults approx. 400 mg,
Children (under 50 lbs) 100 - 200 mg (Please consult your
doctor)
* [ Over the past year several changes have taken place. Please let us know if you feel that your disease response may have changed due to any of these product changes or if the fact that I3C is now only available in capsule form has impacted your ability to get your child to take it.]
The digestive process is important to properly break down I3C (see RRP Newsletter - Spring 94 ). In this regard, try to avoid taking antacids and it is probably best to take I3C at meal time. It has also been suggested that taking ascorbic acid (vitamin C) along with I3C will produce ascorbigen, which some investigators (Preobrazhenskaya, et al., 1993, Food Chemistry, 48,48-52) speculate may be an even more important anti-carcinogen than I3C.
If you do not appear to be responding to I3C, you might want to give bis(3-indolyl)methane (B3IM) a try. B3IM is one of the key reactive by-products of I3C. It can be ordered through Theranaturals by asking specifically for the B3IM CAPS.
Some people have asked whether the I3C in the capsules are derived from natural products such as cabbage and broccoli. The Theranaturals products are chemically synthesized to exactly match natural I3C. The only guaranteed natural alternative is to juice up cruciferous vegetables (i.e., cabbage and broccoli), however, there is another I3C capsule made by Enrich that may be at least partially natural (it is also much more costly). If you would like more information about this product, please call support group member Michael Green at (206)361-8185.
Finally, no matter what product one is using the best way to extend the shelf life is to keep them in a cool dark location such as the refrigerator.
......................................................................................
There has been some speculation that a product from the ShapeRite nutritional supplement company may help control papilloma growths. This speculation is based strictly on the anecdotal response of a couple of patients. If you would like more information we suggest that you call the RRPF west coast coordinator, Susan Spock at (619)697-2332. The ShapeRite company can be reached directly at (801)562-3600, however, Susan can provide you information that will allow one to get a discount on the product.
......................................................................................
by
Bill Stern and Chris Neuberger
The RRPF continues to follow the mumps vaccine as an adjunct treatment for RRP. The therapy involves local injection of the mumps vaccine into the larynx after laser removal of papilloma. (Details of the protocol developed by Dr. Nigel Pashley may be found in the Fall 96 Newsletter issue.) To date there has been no carefully controlled study or clinical trial, so this report is based on anecdotal information provided to us by several doctors and patients.
Dr. Pashley has had the most experience by far among RRP practitioners. To date he has injected 13 patients with the mumps vaccine and claims that 9 patients have had a complete response and a partial response in another patient. We did have an opportunity to talk with the patient who has had a partial response. He has had four treatments and at each successive mumps vaccine treatment thus far fewer papilloma have been found. In an attempt to better understand how the mumps vaccine works, Dr. Pashley has been collecting a history of tissue specimens from his patients. In collaboration with a pathologist, they are looking for markers in the tissue samples that would indicate a level of local immune response. Dr. Pashley encourages other doctors who try this therapy to also keep a tissue sample history of their RRP patients. For more information contact:
Nigel Pashley, MD
1601 East 19th Ave.
Suite 5500
Denver, CO 80218
phone: (303) 839-7900
fax: (303) 839-7930
Two other doctors have reported to the RRPF that they have recently tried the mumps vaccine treatment on some of their patients. Dr. Parsons of the University of Missouri told us that he has injected six pediatric RRP patients with the vaccine, some multiple times, but has not seen a positive response in any of these cases. Dr. Lauren Hollinger, of Children's Memorial Hospital in Chicago, has very recently injected one child with the mumps vaccine, but it is too soon to tell if there was any positive impact. Dr. Hollinger has expressed an interest in conducting a controlled study, but as yet has not put together any specific plans.
Please let the RRPF know of your experiences with the mumps vaccine.
......................................................................................
by
Bill Stern and Chris Neuberger
In the Fall 95 issue of the RRP Newsletter Allan Abramson, MD and Virginia Mullooly, RN, MSN, described the protocol for a new study using photodynamic therapy for RRP at the Long Island Jewish Medical Center Department of Otolaryngology (LIJ). The study is sponsored by the NIH and has involved the use of a new photosensitizing drug, meso-tetra(hydroxy)phenl chlorin (m-THPC). The following update is based on recent discussions with Dr. Abramson, Ginny Mullooly and Dr. Bettie Steinberg.
Two key reasons for using m-THPC versus the previous agent (photofrin) are: 1. The light sensitivity is much less (~3 weeks vs. ~ 2-3 months) 2. The drug allows for greater selectivity getting more in the papilloma and less in other tissue areas. Since the Fall 95 report, a pilot study was started and is currently in progress with 6 patients enrolled. Of the 6 patients, 5 have been treated with m-THPC and two are far enough along to make some assessment of preliminary results (i.e., they have now been observed for at least 6 months following the PDT). Of the two, one had papillomas at three months after surgery, however after the papillomas were removed the patient had no re-growth three months after the first removal. In the second patient the PDT appears to have had no positive impact.
The FDA has just recently approved expansion of the study to 24 RRP patients, including children. In addition, funds to reimburse patients for travel expenses to LIJ have also been approved. Participation in this study will involve a 6 month pre-PDT observing period and a 12 month post-PDT follow-up at LIJ. Patients/parents interested in more information should contact Ms. Ginny Mullooly, Research Nurse Clinician, at (718)470-7011. They can also arrange to send their medical records for evaluation to the following address:
Dr. Allan Abramson
Dept. of Otolaryngology
Long Island Jewish Medical Center
270-05 76th Ave.
New Hyde Park, NY 11402
...............................................................................
The RRPF invites patients and doctors to learn more about these and other experimental therapies. Before entering any experimental trial, we suggest that you make inquiries regarding details of the protocol, all possible side effects, expected impact on papilloma growth, etc. The RRPF cannot endorse any specific therapy, as the applicability of any treatment must be assessed within the context of each individual situation. The information given above is intended to provide some guidance.
HLA Typing in Pediatric Patients with
RRP
by
Nancy Bauman, MD, Richard Smith, MD,
Diane Burke RN, BSN
Blood samples will be collected on pediatric patients followed at the UIHC who have RRP and also their siblings. Specimens will be analyzed by a special laboratory as to the Haplotype (a chromosomal segment of linked genes) present. In a recent study it was demonstrated that 75% of all patients with RRP expressed a specific HLA haplotype (HLA-DQW3) (Bonagura et al. at LIJ) This incidence is remarkably higher than that of the general population.
HLA haplotypes will also be correlated with
severity of disease, and response to adjuvant therapy. Should a
predominant HLA haplotype be evident by analysis of our data, this
information may serve as a pilot study for a multi-institutional
investigation with NIH funding to explain predilection to disease
transmission and, perhaps, prognosis of response to adjuvant therapy
in children with RRP.
Funding Source: Obermann Center for Advanced Studies
Spelman Rockefeller Grant (Univ. of Iowa)
by
Richard Smith, MD, Nancy Bauman, MD,
Harry Hoffman, MD, Diane Burke RN,
BSN
In this study, biopsied tissue samples of adult and pediatric patients will be taken at the time of surgery. The samples will then be screened for selected co-viral infections (Herpes simplex virus types I & II, Varicella Zoster virus, Epstein-Barr virus, and cytomegalo-virus), to identify the subgroup of patients expected to benefit from antiviral therapy with Acyclovir. The successful use of Acyclovir in the treatment of RRP reported in several recent studies was unexpected and has been taken as indirect evidence of viral co-infections (Aquado et al, 1991; Endres et al,1994; and Morrison & Evans 1993).Funding Source: GlaxoWellcome Pharmaceutical Co.--pending
.......................................................................................
Studies continue by Drs. Thomas Broker and Louise Chow to further develop HPV specific culture systems and use them to evaluate the effects of known antiviral agents on HPV replication.
.......................................................................................
by
Karen Auborn, Ph. D.
Long Island Jewish Medical Center
The National Cancer Institute now supports a research project of Dr. Karen Auborn at Long Island Jewish Medical Center to investigate dietary compounds that are useful in the prevention and treatment of papillomavirus induced lesions. With this funding, Dr. Auborn continues studying the mechanisms of action of indole-3-carbinol from cruciferous vegetables. Other compounds include omega-3-fatty acids from fish oils and certain isoflavinoids from soy products. These compounds theoretically could be useful.
Preliminary laboratory studies indicate that the omega-3-fatty acids are promising, although no animal studies have been done with the fatty acids as yet.
......................................................................................
edited by
Bill Stern
The thought of an inoculation that would be capable of effectively controlling and preventing RRP is a wonderful dream. Although we are not likely to see this dream become reality in the near future, there is some encouraging research taking place that at least provides some hope for the future.
In the past some attempts were made to inject a patient with their own papilloma in hope of getting an antibody response. Generally, this approach was unsuccessful. Another "vaccine" approach which has and still is being used as an adjunct treatment for HPV, is to inject a patient with immune system stimulants such as Interferon and Imiquimod (and perhaps the Mumps vaccine should also be included under this heading). These treatments have demonstrated some limited success, especially Interferon. However, they do generally involve a continuous treatment approach accompanied by annoying side effects some times.
Of particular interest to the RRP community (and for that matter to anyone involved with HPV disease expression) is the development of a vaccine for HPV 6 & 11 disease (TA-GW ) by a research group headed by Dr. Stephen Thompson at Cantab Pharmaceuticals in the United Kingdom. The unique part of their vaccine is that it is designed to be a therapeutic vaccine, i.e., to treat those with disease. It may also have some prophylactic utility but that remains to be seen. Two other pharmaceuticals, Merck and Medimmune, are also developing HPV vaccines. Both of these companies are developing products around virus like particles (VLP's) designed to elicit neutralizing antibodies and protect from infection, but not necessarily designed to "cure" existing disease. In comparison with attempts in the past to use patients own papilloma, the theory for TA-GW is very similar. However, in contrast to the somewhat unmeasured situation of "grinding up" a patient's own papilloma for a vaccine, TA-GW is a non-infectious recombinant protein that can be delivered at an efficacious dose with an appropriate adjuvant. It should be simpler, more effective, safer and more reliable than the preparation and immunization strategies with patients' own papilloma.
Cantab's product strategy for treatment of genital warts is based on recent findings from a model system, which indicated that cattle wart regression could be accelerated by therapeutic vaccination with certain papillomavirus antigens (Beatson Institute of Cancer Research, Glasgow), and that spontaneous regression of genital warts in humans is characterized by a vigorous immune response at the site of the lesions (Cambridge University and St Mary's Hospital, London).
TA-GW involves a recombinant protein comprising a fusion of the L2 (minor capsid protein) and the E7 proteins of HPV 6. It is designed to induce an immune response in humans that can recognize and destroy the infected tissue, and hence eliminate papilloma recurrence. Since the product is administered by conventional vaccination procedure, rather than by direct application to the site of the lesion, it should be appropriate for treatment of all genital (and presumably respiratory) papillomas, regardless of their accessibility. Furthermore, TA-GW might possibly provide continued protection against re-infection by HPV at a later date.
Phase I studies of TA-GW in 1995 showed that the product was safe and immunogenic in healthy male subjects. These studies further identified a dose and vaccination schedule for the product. The first in a series of Phase IIa studies included 27 males with either persistent/relapsing or newly presenting genital warts. The trial was successfully completed at the end of 1996. All patients received 3 intramuscular injections over a 4 week period. At week 8 total wart clearance was seen in 3 patients who received TA-GW only plus 3 others who were receiving a conventional therapy as well. Those still presenting papillomas were continued on a conventional treatment with 8 additional patients being cleared. Further Phase IIa trials in patients with genital warts or respiratory papillomatosis, are ongoing in collaboration with SmithKline Beecham Biologicals (SB Bio), Rixensart, Belgium.
Recent studies at LIJ, have suggested that HPV may block the cell surface signals that allow the immune system to recognize infected cells, thereby not activating cytotoxic T cells ("killer cells") necessary to destroy the infected cells (Steinberg, personal communication). This may be particularly true in RRP patients and others whose disease does not regress spontaneously. In this regard it is important to include RRP patients in a trial using TA-GW to see if it can be an effective treatment for RRP.
Further studies with Dr. Bongura at LIJ are underway to better understand why RRP patients do not clear infections and whether their "killer cells" can be stimulated with viral proteins
Acknowledgments: I would like to thank Dr. Stephen Thompson of Cantab for providing the RRPF with much of the information used in this article. Thanks also to Drs. Keerti Shah, Bettie Steinberg and Tom Broker for providing additional material and helpful discussions.
[In this newsletter issue we present RRP experiences and perspectives of Michelle Mangrich. Michelle's article is based on her replies to a customized interview designed by Diane Burke, RN . ]
I was 20 years old when I was first diagnosed with RRP in 1986. My first three surgeries were done with a scalpel by a doctor in Waterloo, Iowa. This doctor also ran allergy tests and gave me allergy shots, which did nothing to improve my RRP. Since then I've had four more surgeries done by laser in Iowa City at the University of Iowa by Dr. Harry Hoffman. After each surgery my voice has been clear and strong. I am very happy with the way I sound after surgery. I've been told I have a deep, sexy voice. I laugh and say I wouldn't recommend going through what I do to have a sexy voice. I have tried both interferon and I3C, but neither has helped me.
I am a wife, mother of three children, help run a busy farm, and work part time for the U.S. Post Office. I had no problem with the RRP when I was pregnant with my boys. However, when I was pregnant with my little girl I had to have surgery when I was 18 weeks along. The doctors felt that having surgery was less risky than not having it, as the papilloma were obstructing approximately 80% of my airway and I was looking at an emergency tracheostomy. This was probably the lowest point in my experiences with RRP. I couldn't talk, eat, or breathe without sounding like I was struggling for a breath, yet I feared for my baby's health because of the surgery. I won't let myself get that bad again. Whenever I have a bad day I look at my kids and thank God that I have RRP instead of them, and get myself so busy that I don't have time to feel sorry for myself.
Dr. Hoffman is very careful about not being too aggressive during surgery. I've learned so much about RRP from both Dr. Hoffman and Diane Burke. They've helped to teach me that you have to accept it and live each day with a smile on your face, and cherish the good things in life. Do I have any words of wisdom to my family and friends? Yes, please be patient, loving, and understanding to us. I know it's hard to hear us at times. Sometimes we just need a hug rather than hearing "What did you say? I can't hear you." My advice for patients is to find out as much about RRP as you can. Enter as many studies as you can. We have to help each other out. There will be a cure for us someday. Keep your spirits up. God is on our side.
Michelle Mangrich
5505 Sringcreek Road
Jesup, IA 50648
(319) 827-3774