Vol.3 No.2 An RRP Foundation Publication 1994 Fall
____________________________________________________________________________________________________
Contents
• Opening comments - p. 1, memorials- p. 1 & 8
• Officers, Board Members and Advisors - p. 2
• RRP Network News - p. 2
• RRP Perspective: Life Insurance for RRP kids - p.3
• Patient Statistics - p. 3
• RRP Task Force and RRP Registry - p. 4
• Update on Adjunct Therapies and new protocols:
Indole-3-Carbinol - p. 5
Ribavirin: new randomized study - p. 6
Interferon Revisited - 3 new studies - p. 6
"Improved PDT" - p. 7
• RRP/HPV Research Activities
Univ. of Pittsburgh: Need for Pap specimens - p. 7
• Patient profile - p. 8
• RRPF Mission Statement, Information/Support Centers, subscription form - enclosure

From the Editor

This issue of the RRP Newsletter is dedicated to two patients in our support group who have passed away this year, Roger Kirby, age 23, and Tracy Brooks, age 4. A short memorial for Tracy, which appeared in the RRP Summer Update issue, is repeated on the back page of this issue. May their courageous struggles with RRP inspire us to find a cure for this disease.

The RRP Newsletter is vital to our support services and networking efforts. We welcome your comments and suggestions. Your feedback will be very helpful in improving 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) Thank you.
Bill Stern

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. In the premier issue published early this year, nearly 400 RRP related references were listed, with selected abstracts for the more recent listings. The mid-year update provided an additional listing of 37 RRP related references and abstracts. Our plans are to continue these semi-annual updates, with periodic listings of all references in our database.
We are asking for your help in supporting these publications and other RRP services including patient outreach, support and advocacy. Due to funding limitations, we find it necessary to institute the following subscription policies -
Minimum Annual Donations
RRP Newsletter
Professional/Corporate - $25
Individual - $15
RRP Newsletter plus RRP Medical Reference Service
Professional/Corporate - $40
Individual - $25
(see RRPF subscription form enclosed)
As long as funds permit, we will make every effort to continue sending the RRP Newsletter to members of the RRP patient support network who indicate an interest but are unable to make a donation.
We are most grateful to all those individuals and medical professionals who have supported the RRPF. Future donations from individuals, professionals or from the business community will be very much appreciated. Tax deductible contributions may be made to:
RRP Foundation
50 Wesleyan Drive
Hamilton, NJ 08690
Do you donate to the United Way through your employer? There is now a "Donor Choice" option which would allow you to direct a donation to the RRPF as the 501 (c) (3) of your choice.

In Memory of Roger Kirby

After more than two decades of struggling with recurrent respiratory papillomatosis, on June 12, 1994 Roger Kirby II died of cancer which developed from papilloma in his lungs. Roger was originally diagnosed with RRP at the age of one. His disease was quite aggressive, as he endured about 200 surgeries in his lifetime.
He is survived by his mother Shari, father Roger and sister Rachel.

To physicians and nurses: Please distribute copies of this newsletter to your RRP patients
Please register with the RRPF by completing the Practitioner Questionnaire



RRPF Officers, Directors & Advisors

Marlene Stern
President
50 Wesleyan Drive
Hamilton, NJ 08690
(609) 890-0502

Bill Stern
Treasurer and Director
50 Wesleyan Drive
Hamilton, NJ 08690
(609) 890-0502

Henry Woo
Secretary
600 New Hampshire Ave., N.W.
Suite 720
Washington, D.C. 20037

Diane Burke
Director
Department of Otolaryngology
The Univ. of Iowa Hospitals and Clinics
E230 GH, 200 Hawkins Drive
Iowa City, IA 52242
(319)356-1765

Susan Woo
Director
7107 Georgia St.
Chevy Chase, MD 20815
(301)652-6826

Scientific Advisory Committee

Thomas 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

Bettie M. Steinberg, PhD, Long Island Jewish Medical Center

Kathleen Sullivan, RN, Children’s Hospital of Boston

Representatives of the RRPF will be there, at Booth #651. If you are in the neighborhood, stop by and see us.



New RRPF Director Profile

We are pleased to announce the appointment of Diane Burke, RN, BSN, to the Board of Directors of the RRP Foundation. A brief summary of her background, experience and interests follows below.


Diane Burke has been in the nursing field for 16 years. Her background includes: Critical Care, Recovery, Operating Room, Nursing Instructor at two colleges and research. Most recently she has found her niche as a Pediatric Nurse Clinician in the department of Otolaryngology at the University of Iowa Hospital and Clinics in Iowa City, IA. She feels her role as an RN in supporting and caring for patients and families dealing with chronic illness has been very fulfilling. Diane is currently following approximately 25 patients with active RRP (this includes both juvenile and adult cases). In addition she has been part of several clinical research projects, including co-authorship of a recent paper about the use of a protocol involving acyclovir to treat RRP patients.
Apart from being a nurse, Diane (and her “great helper-husband Tim”) love being parents to their six year old son, Daniel, and two year old daughter, Rachel.

RRP Network News
Patient/Family Support Network:
Our national support network has grown to approx. 140 respiratory papilloma families. Patients range in age from 6 mo. to 76 years and are located in 31 states, two Canadian provinces and Great Britain.
We have received questionnaires from about 70% of the families in the support group. If you have not filled out a questionnaire or adjuvant therapy survey as yet or would like to provide updated information for the RRP Foundation Patient/Family database, please take a few minutes to fill out the accompanying forms to the extent needed to bring the information about yourselves up-to-date. Please return them to Marlene and Bill Stern. In addition, RRP families, please review the Patient Directory listings and notify us regarding any corrections, ommissions or additions.
Communication among support group members remains a primary focus of the foundation. The RRPF maintains an account with America-On-Line (AOL) and also has access to Internet We can arrange for you to have a limited amount of free time on AOL to communicate your questions, comments and/or suggestions; just get in touch with Bill Stern. Let us know of any ideas regarding additional ways to provide for cost effective communication among members of the RRP community.

RRP Perspective

Life Insurance for RRP Kids
by Cheryl Downey

While this country is currently entertaining proposals to implement universal health coverage, regardless of pre-existing conditions, no such enlightened paths are being pursued in the life insurance field.
While many of us affected by RRP are parents of young children, and normally would not be very concerned about purchasing life insurance for our youngsters, we should not ignore the chronic reality of RRP and the subsequent difficulties our children may have down the road when they need life insurance to protect their own families.
With insurance practices being as traditionally conservative as they are, it behooves all of us "RRP parents" to insure our RRP-affected children now with policies that provide for several opportunities to raise the amount of coverage without a health exam being required.
I recently purchased a Universal Life policy on my 2 1/2 year-old daughter, Ariel Bandasch, which guarantees that the amount of coverage can be raised incrementally at various ages up to age 40, with no health questions asked.
An added benefit in the particular policy I selected, allows me (or Ariel, later) to make additional contributions in the investment portion of the policy and under current laws the earnings are tax deferred.
I feel most relieved and grateful that Ariel was granted this policy with no exam and no extensive investigation (the usual case with young children). And while I continue to lobby and pray that a cure for RRP will be found long before Ariel turns 40, I can rest easier knowing that I've protected her right to decent life insurance despite her congenital condition.

RRP Patient Stats

The statistics that follow are based on RRPF patient and practitioner questionnaires. 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, we direct you to the information presented by Craig Derkay, MD for the Task Force on Respiratory Papillomas, at the Otolaryngological meeting held in Palm Beach, FL, this past May. A summary of his presentation is included in the article on pages 4-5.

Tables 1 - 4 provide a breakdown of the patients in the support group based on sex and age; the sample size for these tables is 140 (as of August 1994).

Table 1. Total number of patients in support group

	Females	Males
All Ages	66	74

Table 2. Distribution of patients based on current age brackets and sex

Age Groups	Females	Males	Total
Under 10	35	30	65
10-20	15	15	30
20-30	4	5	9
30-40	7	2	9
40-50	1	11	12
Over 50	4	11	15

Table 3. Distribution of patients based on diagnosis age brackets and sex

Age Groups	Females	Males	Total
Under 10	54	48	102
10-20	3	2	5
20-30	6	3	9
30-40	0	8	8
40-50	2	8	10
Over 50	1	5	6

Table 4. Birth Statistics from Patient Support Network:

Cesarean birth in 3 cases - 87 responses
juvenile onset: 2 of 68 responses
adult onset: 1 of 19 responses
Patient is first born in 50 cases - 79 responses
juvenile onset: 45 of 63 responses
adult onset: 5 of 16 responses
Patient was adopted in 19 cases- 86 responses
juvenile onset: 19 of 75 responses
adult onset: 0 of 11 responses
Mother’s ages - 31 responses
20 or under: 12 of 31 responses
20 -> 25 : 11 of 31 responses

Thus far we have received practitioner questionnaires from about 40 otolaryngology departments who are treating RRP patients. There is a total of approximately 952 patients, 475 pediatric and 477 adults. A breakdown of some of this information is presented in tables 5 - 7.

Table 5. Females and males (based on 608 patients)

	Females	Males
All Ages	247	361

Table 6. Surgical interval (based on 524 patients)

	< 2 mon.	2-12 mon.	> 12 mon.
All Ages	124	302	98

Practitioner responses to date have indicated that 252 of the approx. 952 patients in their practices are following (or have followed) other therapies in addition to surgical removal of papillomas, with a breakdown as follows:


Table 7. Distribution of adjunct therapies used

IFN	Acyc	Indoles	Retinoid	PDT
119	14	27	4	87

In addition ultra-sound has been used on one patient.

Task Force and RRP Registry

The following is a summary of information presented at the annual Spring meeting of the Otolaryngology Societies held in Palm Beach Florida this past May. It is based mostly on findings and background info. provided by Craig Derkay, MD (Eastern Virginia Medical School), who is heading the Task Force on Respiratory Papillomas, plus some additional input from RRPF board member and clinical nurse Diane Burke, RN, BSN (Univ. of Iowa Clinics and Hospital).

A meeting of the RRP Task Force was held on Tuesday May 10, 1994 and findings were also presented on Wednesday May 11 at a joint scientific session of the ASPO (American Society of Pediatric Otolaryngology) and ABEA. (American Bronchial and Esophageal Association).
The Tuesday meeting was co-chaired by Dr. Derkay and Dr. Bill Reeves of the CDC (Centers for Disease Control and Prevention). In attendance were 14 nurses and/or doctors from medical institutions that would be expected to be active participants in the second phase of the RRP National Registry project. In addition to Diane Burke, RRPF advisors Linda Miller, RN, MSN (Children's Hospital of Philadelphia) and Kathy Sullivan, RN (Children's Hospital of Boston), were among those who were attending.

Some of the major topics discussed were:

1. Purpose of the Task Force on RRP -
• To estimate the incidence and prevalence of RRP among children and adults in the United States.
• To estimate the current state-of-the-art, regarding management of RRP.
• To estimate the financial cost of the disease.
• To help establish a national registry of RRP patients for future studies and as a source of tissue specimens for basic research.
• To establish a consensus regarding management of the "at-risk" pregnant woman with genital tract papillomas.

2. Summary of the analysis of data received from an initial survey of the otolaryngology community conducted during the past year. The surveys were sent to a "representative" subset of all otolaryngologists in this country and the findings are based on extrapolations from 312 respondents (24% of total sent).

• Estimate of number of new cases of RRP in the U.S. per year:
2500 pediatric and 3200 adult
• Estimate of number of active (at least one surgery in past 3 years) RRP cases in the U.S.:
5300 pediatric and 8500 adult
• Estimated incidence (new occurrence) in the U.S.
pediatric = 4 / 100000 and adult = 1.6 / 100000
• Estimated prevalence in the U.S.
pediatric = 9 / 100000 and adult = 4.2 / 100000
• Estimate of number of surgical procedures for RRP per year in the U.S.
17000 pediatric and 10000 adult
• Annual health care cost estimate in the U.S. comes to 157 million dollars, approximating a total cost per procedure at $6647 for children and $4500 for adults.

• Pediatric RRP associated with more frequent surgeries.
• Preferred method of surgical management was microlaryngoscopy with CO2 laser - used by 92% of respondents.
• No consensus on anesthetic management during laser surgery.
• Preferred adjunct therapy was interferon, used to treat 9% of children vs. 1% of adults.
• “Need” for tracheotomy
14% of children vs. 6% of adults
• Incidence of extralaryngeal spread
31% of children vs. 16% of adults.
• Development of squamous cell carcinoma has been diagnosed in 26 known patients. RRP is known to have developed in one transplant patient and four AIDS patients.

• Lack of consensus on use of cesarean section to prevent transmission. When asked “Do you favor the use of a cesarean section in a woman who had previously delivered a child with RRP and is now pregnant for a second time?”, 23% of the otolaryngologists responding said yes, 19% said no and 58% offered no opinion.
• From all of those responding only four sets of siblings having RRP were discovered.
• RRP was reported in both members of one twin set and only one member of another twin set.
• Several cases of newborns and very young infants with RRP have been found, evidently indicating that in these children there was likely an intra-uterine infection process.

3. In the Second Phase 15 geographically diverse major medical centers within the United States, have been chosen to participate in an extensive research project. This study will consist of a detailed analysis of recurrent respiratory papilloma cases at each center, and is proposed to involve personal interviews between nurse/practitioners and papilloma patients/families in a confidential setting. Information obtained in this way will serve as initial entries into the national registry of recurrent respiratory papillomatosis. The registry will serve as both a tissue registry as well as a means of studying transmission factors and treatment modalities and is hoped to be established over a three year time period.
There still is not unanimous agreement regarding the details of this phase. In particular, some nurses and doctors feel that confronting the comprehensive six page questionnaire (which does contain some sensitive and explicit questions) in a dialogue situation with the RRP patient or family, may be too intimidating as well as demanding of their time. An alternative proposal might be to “register” the patient via a simple one page form, give them a copy of the comprehensive questionnaire to fill out as best they can at home and then complete the process the next time they come for surgery.

4. Support for the National Registry Project is being pursued through the efforts of Bill Reeves, at CDC in Atlanta and Penny Hitchcock at the National Institute of Allergy and Infectious Disease. It is hoped that NIH will support a request for $75000 per year for a 3 year unsolicited contract to develop the database and continue the second phase of this project. Bill Reeves has also offered CDC’s expertise and guidance for initiating the national registry. [ Ed. Note: In addition, in conversations with RRPF advisor Dr. Tom Broker, I have learned that the University of Alabama Bio-Statistics department is quite willing to offer their expertise in support of this effort.]

Adjunct Therapy and Protocol Update

The following reports of clinical research involving RRP therapies, represents a best effort to make an accurate and objective presentation of information from articles submitted by investigators, personal communications and/or reference to literature. Where appropriate the RRPF has provided its input in a constructive manner which we hope will best serve the RRP community.

Bill Stern
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The RRPF has already written extensively 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 and Spring 94 as well as Newfield et al., 1993, Anticanc Res 13:337-342).
In the Spring 94 RRP Newsletter issue, the RRPF published some preliminary results of a Long Island Jewish Hospital (LIJ) trial involving cruciferous vegetables, which typically contain varying amounts of I3C. What remains as one of the most robust findings of this study is the apparent existence of a nearly linear relationship between the ratio of estrogen metabolism pathways¹ and the severity of RRP disease, as determined from baseline urine analyses (Dr. Karen Auborn, personal communication). Preliminary data from approximately twelve RRP patients enrolled suggest that ratios of less than 1 are associated with more aggressive disease while ratios of 3 or greater are associated with much milder RRP. It would be of interest to compare these data with those from Dr. Leon Bradlow’s general population estrogen metabolism studies (Strang Cancer Research Institute). [ Ed. Note: Our daughter,Lindsay now nearly 5 years old, has followed the crucif. vege. protocol since April 1992 and has been using pure I3C since February of this year. She currently remains in an apparent remission which started in the summer of 1992. Over the last six months her estrogen metabolism ratio values have ranged from 1.25 to 10.7 averaging about 4.5.]
The purpose of the LIJ trial was to determine whether the diet would concomitantly improve disease and change use of estrogen metabolism pathways.
Five patients in the LIJ study have used the diet for greater than one year. Two of these patients are free of disease and one is dramatically improved. The two patients who showed no improvement, did not show any change in estrogen metabolism as a result of the diet. This positive therapeutic impact of the cruciferous diet, is supported by our RRPF adjuvant therapy survey (separate from the LIJ study), which evaluates responses of persons using diet and/or pure I3C on their own. The early responses to the survey, indicate that 8 of 11 RRP patients who have been following an I3C therapy for at least six months have had a lessening of the severity of their disease. In five of the eight cases there has been at least a doubling of the period between surgeries. It should also be noted that in two of the eight cases there was no positive response until the patient had switched from cabbage to pure I3C.
From a research perspective, Dr. Auborn's work at LIJ is clearly suggesting that I3C should play a role in treating humans with RRP. However, the time has come to more precisely define an I3C therapeutic protocol, and the RRPF believes that this can only be accomplished through a carefully controlled clinical trial involving pure I3C . There is just no practical way of carefully quantifying the amount of I3C a person is getting at any point in time when they obtain it by ingesting cruciferous vegetables, even when the amount is precisely quantified. In this regard the RRPF strongly recommends that LIJ do what is necessary to use pure I3C in a therapeutic clinical trial. This suggestion is consistent with that of Dr. Leon Bradlow, whose estrogen metabolism studies have been done with pure I3C and could be used to establish dosages for an I3C clinical trial. If asked the RRPF would be happy to help in trying to expedite FDA approval of I3C as an investigative new drug for RRP therapy.

¹ This measure is defined as the ratio of 2-hydroxylation (the "tumor suppressor" metabolic pathway) to that from 16a-hydroxylation(the "tumor enhancer" pathway).

While we wait for more definitive research results, the RRPF encourages patients to supplement their diet with I3C, after consulting with their physicians. Approximate dosing information ( using estimates obtained from preliminary results of Dr. Leon Bradlow's estrogen metabolism studies) and sources, are listed as follows:
Estimated dosages - Adults 200 - 400 mg, Children (under 50lbs) 100 - 200 mg (Please consult your doctor)

Sources:

1. Enrich International (formerly Enhanced Living)
748 North 1340 West
Orem UT 84057
to order products: (800)748-4334
distributor #: (801)226-2224

Their product is called Nutrin-3 (product #732) it comes as a bottle of 100 capsules ($77.95) and each capsule is guaranteed to contain at least 100 mg of indoles. You can get a significant discount on price ($20 at current pricing) by becoming a distributor.

2. Designed Nutritional Products
145 N. Geneva Rd.
Vineyard UT 84058
(801)224-4518

Designed Nutritional Products is a division of Parish Chemical. They produce nutritional products in bulk including pure indole-3-carbinol (catalog #2704). It can be purchased in 25 gram amounts (bulk powder, not capsules - a level 1/8 tsp holds approx. 350 mg) for $46.50 + $5 shipping (pricing as of May 94). They are not equipped for credit card orders, so one must pay by check. The check should be made out to: Designed Nutritional Products and mailed to the address above. Include a note explaining that you want to order indole-3-carbinol catalog #2704. For those interested in very large quantities, you can inquire about the price of a kilogram of indole-3-carbinol.
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by Ronald C. McGlennen, M.D.

Human papillomavirus infection is associated with the development of benign and malignant tumors of the skin, anogenital and ororespiratory tract, for which there is no known curative method of treatment. However, our group, based at the University of Minnesota and lead by Drs. Ron Ostrow, George Adams and Ron McGlennen have experienced some promise in treating ororespiratory papillomatosis with the medication Ribavirin ™ (1-b-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), a nucleoside analogue, for the antiviral treatment of HPV infected tissues. Based on early experimental success with Dutch belt rabbits infected with Cottontail rabbit papillomavirus (CRPV), which produces cutaneous warts, moderately high doses of intradermally injected ribavirin were found to be extremely effective at preventing the appearance of measurable warts in animals treated at the time of virus infection and also reduced the rate of wart growth in animals with established warts. This indicated that ribavirin might also be an effective antiviral agent for human papillomavirus-induced disease. A recently completed uncontrolled pilot clinical trial of intravenous/oral ribavirin treatment in four patients severely affected with long standing laryngeal papillomatosis appear to show ribavirin to be an effective adjunct to laser extirpation of ororespiratory tract papillomas. All four patients responded with a partial or complete clinical remission of papillomatous growth, thereby reducing the need for frequent laser surgeries. Subsequently these results have recently been published ¹. The side effects of ribavirin treatment were minimal and readily reversible. The principal one was mild red cell anemia and occasional complaints of headache.
We are now initiating a new study with ribavirin using a two-armed protocol. This new study will be conducted as a phase II double-blinded, controlled crossover trial of two years duration on thirty-five patients exhibiting aggressive infantile, juvenile or adult laryngeal papillomatosis. The goals of the study are twofold: first we will be again concerned about demonstrating efficacy of the intravenous/oral combination of ribavirin. To do this we will be examining as our primary end point, the duration of time between needed laser surgeries as determined by patient defined symptoms. Secondly, we will be measuring lung function tests, and quantifying the extent of the disease in the airway by computer assisted mapping of papillomas. Other issues such as the HPV type, patient specific factors such as age, sex and HLA (Human Leukocyte Antigen) type will be correlated with the clinical results.
Based on the results of our two earlier studies we are hopeful that ribavirin will prove itself to be useful in prolonging the interval of time and the symptoms related to ororespiratory papillomas. The investigators welcome questions regarding this ongoing study and request that inquiries be directed to:

Ronald C. McGlennen, M.D.
Department of Laboratory Medicine and Pathology
Box 609 UMHC
420 Delaware Street S.E.
Minneapolis, MN 55455
612-625-2126
FAX: 612-625-6994
email: mcgle001@maroon. tc.umn.edu

¹ McGlennen R.C, Adams GL, Lewis CM, Faras AJ and Ostrow R.S. A pilot trial for the treatment of laryngeal papillomatosis. Head and Neck 15:504-13, 1993.

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Interferon has been used in the treatment of RRP patients for more than a decade, with varying degrees of reported effectiveness. A scan of literature reveals different dosing strategies, different types of interferon and different measures of efficacy. In addition, interferon is not without side effects; they are reversible and most are tolerable, but in some cases treatment must be discontinued. For more information interested readers are referred to Healy et al., N. Engl J Med, 1988, 319:401-7; Leventhal et al., N. Engl J Med, 1991, 325:613-617; and an unpublished review article by Rosen, 1993, recently distributed by the LPAP.
The following update involves proposed or recently started studies that hope to improve on some aspects of earlier trials.

Pablo Stolovitzky, M.D., at ENT of Atlanta, has proposed a research protocol for RRP treatment with Interferon directly injected into papilloma sites. In an uncontrolled test there has been at least one patient who appears to have had a very positive response to local injections done only at the time of laser surgery. By delivering the interferon directly to the papilloma, the hope is to improve efficiency of the treatment with a significant reduction in side effects. The initial proposal would involve scheduling injections (and laser surgery if necessary) at least every other month. Christina Lancaster (an RRP patient and member of the support network) is actively involved in seeking a source of interferon for this project. Anyone interested in participating and/or finding out more details, should contact:

Christina Lancaster
186 Pine Knoll Lane
Eatonton, GA 31204 (706)485-1016
e-mail: 75230.1612@Compuserve.com

RRPF Advisor, Robert Ruben, M.D., has recently learned of a new interferon (IFN) study being conducted by Dr. Desloovere’s group in Frankfort, Germany. The following report is based on Dr. Ruben's assessment of a presentation made at the Sixth International Congress of Pediatric Otolaryngology.

Although many details about this protocol are not known to us at this time, a key uniqueness appears to be the use of an objective approach of customizing dosages and maintaining efficacy for individual patients. They are using an enzyme assay to monitor the activity of the IFN. They reportedly stop this IFN therapy at that time when not only all visible papilloma disappear, but also the surrounding tissue is free of HPV. This enzyme assay approach follows one described in a German language paper by Gerein et al. (Klin. Padiat., 1987, 224-229), in which IFN dosages for each RRP patient was determined using the induction kinetics of (2’-5’)-oligo(A)synthetase (OAS) in mononuclear cells of the patients’ circulating blood.
We will await more details regarding the protocol used in this study and any preliminary results.

Early this summer, Haskins Kashima, M.D. (RRPF Advisor) submitted a proposal for a new carefully controlled multi-center interferon study. This study would be coordinated by Johns Hopkins and would involve some 20 other institutions around the country. At this time the proposal is currently being evaluated and reviewed by several federal funding agencies.
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Photodynamic therapy (PDT) has been used to treat respiratory papillomas at LIJ since 1986. In 1988 a clinical trial was started using the light sensitive dye dihematoporphyrin ether (DHE). It is reported in Abramson et al., 1992 (Arch. Otolaryngol. Head Neck Surg. 118: 25-29), that on average, there was a approximately a 50% reduction in the growth rate of respiratory papillomas, at least throughout the one year follow-up period. A significant side effect was prolonged light sensitivity, which in a number cases lasted three months or more.
Recent animal studies using another photosensitizer, meso-tetra(hydroxyphenl) chlorin, indicate much greater absorption of the dye by papilloma tissue and a faster "washout" time. The combination of these factors, suggest greater potential for reducing papilloma growth and a reduced period of photosensitivity. These findings were first presented at the HPV meeting in September 1993, by Mark Shikowitz, MD, and recently updated by RRPF advisor, Bettie Steinberg, PhD (via personal communications) for inclusion in the Summer 94 issue of the LPAP Newsletter and this Fall 94 issue of the RRP Newsletter.
Dr. Steinberg is expecting a clinical trial involving PDT with this new FDA approved photosensitive dye, to begin at LIJ within six months. Candidates for this trial must have had at least a one year history of RRP with at least three laser procedures in the last year. The protocol will involve a six month observation period at LIJ prior to PDT surgery and a one year follow-up period at LIJ after the PDT. It is anticipated that funding will be provided to cover travel expenses for those participating in this trial.
For more details please contact:

Dr. Allan Abramson
Dept. of Otolaryngology
Long Island Jewish Medical Center
270-05 76^th Ave.
New Hyde Park, NY 11402
(718) 470-7555

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The RRPF invites patients and doctors to learn more about these and other experimental therapies. Before entering or recommending 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 applicability of any treatment must be assessed within the context of the individual situation. The information provided above is intended to provide some guidance.

RRP Research News

RRP/HPV Research Activities at Children’s
Hospital of Pittsburgh - Request for RRP and Pap Specimens

The following information was provided to the RRPF by HPV researcher Frank L. Rimell, M.D. via letter and phone and is summarized below by Bill Stern.

Several interesting findings relevant to RRP have taken place at the papilloma lab of Children’s of Pittsburgh during the past few months.
A study to relate HPV typing to disease course is currently underway. From a sample of nine children who had required tracheotomies early on due to aggressive disease, seven were determined to be infected by HPV 11, while only two had HPV 6 alone. In addition, of 14 adults with aggressive disease, 11 of 14 had HPV 11 or HPV 6 plus Herpes Simplex Virus. These preliminary results are suggestive that HPV 11 or HPV 6 plus a viral co-infection may be associated with more aggressive (and perhaps earlier onset of) RRP disease. Also they have discovered an occurrence of HPV16 in laryngeal papilloma which eventually became a carcinoma. [Ed. note: It is hoped that this work will expand upon the earlier related study by Mounts and Kashima, 1984, (Laryngoscope 94: 28-33) ].
To statistically enhance the credibility of their results they need to obtain more samples of respiratory papillomas. They are also very much interested in pap specimens from mothers of RRP patients to compare viral co-factors and viral type.
If you would like to participate in on going RRP research as well as obtain comprehensive HPV typing information, please contact:

Dr. Frank Rimell
Children’s Hospital of Pittsburgh
Dept. of Pediatric Otolaryngology
One Children’s Place
3705 Fifth Avenue at DeSoto St.
Pittsburgh PA 15213-2583

Tel: (412)692-5326; beeper #4746
Fax: (412)692-6074


RRP Patient Profile

Stephen Wright, who recently joined the RRP Foundation Support Network graciously agreed to provide his insights and experiences relating to recurrent respiratory papillomatosis (RRP), via a telephone interview with Christina Lancaster.

Stephen is a very personable and accomplished individual who was most open and honest about the various conditions and circumstances of his illness.
He feels strongly that interferon has changed his life, and secondly, that, you should not let this disease interfere with your relationship with your family and kids.
Stephen is an adult onset patient with diagnosis at age 35. The most obvious symptom of papillomas was his loss of voice quality, which is what first clued him in to pursuing an accurate diagnosis. Stephen believes that the papilloma onset began in 1980, with the first reoccurrence in 1982. Fortunately, Stephen has been able to see some of the best Otolaryngologists in the country such as Dr. Stuart Strong, Dr. George Simpson at Boston University hospital and then Dr. Troost at Georgetown University (and later Dr. Haskins Kashima at Johns Hopkins).
Over a ten year period from approximately 1983 to 1993 Stephen's RRP was quite aggressive, especially for an adult. Surgical intervals decreased from approximately 10 weeks in 1983 to only 6 weeks in 1993. He lived with persistent hoarseness, with only the ability to whisper about one third of the time. Despite this severe voice loss, Stephen progressed in his career to the point where he is now President and Chief Operating Officer (COO) of a significant, privately held computer software company, regularly giving speeches to large audiences, often with the aid of a strong microphone. However, during this period Stephen admits to a severe impact on his psyche with some consequent impact on his wife and children. Stephen feels this is when it is most important to fight the tendency to become withdrawn and become hesitant to use your voice. "Your voice quality doesn't matter to your kids, what's important is that you be their parent."
In 1993 with surgeries getting progressively more frequent, Stephen began to seek out ways to reverse this trend. It was at this point in time that he considered using interferon as an adjunct to the surgeries for various reasons; one of Stephen's real difficulties with surgery is that he has difficult veins for IV insertion and it causes him a considerable amount of anxiety as well as pain, and surgery every five to six weeks made it increasingly more difficult for him to continue on with his duties as COO.
In the spring of 1993 Stephen went to Johns Hopkins University to talk with Dr. Brigid Leventhal and Dr. Kashima about their interferon protocol for treating respiratory papillomas.
After a laser procedure in August of 1993, he began interferon (using the Burroughs Welcome product, Wellferon) with a dosage level of 6 to 8 MUs per day . At this dosage level it was not unusual to experience the bad reaction that he had to the first injection, chills, shaking, teeth chattering, flu symptoms tripled, occurring one to two hours after that injection. Stephen puts this all in perspective, “ the side effects are unpleasant, but a hell of a lot more preferable to surgery every five weeks!”
His next laser surgery was not required until November of 1993. Given the doubling of time between surgeries, as well as diminishing side effects, he continued interferon at the same initial dosage. In Stephen's case there was clearly a very positive growth reduction response.
Stephen's most recent surgery was June 3, 1994, seven months since his previous laser excision and he continues using the interferon at the same initial dosage level, but now every other day.
He has experienced over 50 surgeries since diagnosis 14 years ago, but Stephen believes that interferon really can and does make a difference in his treatments. He only takes one other drug to reduce the side effects of the interferon, which he has found to be very effective, Methylphenidate, 5mg three times per day. He says he now has more energy and is able to handle his busy work schedule.
Stephen's last bit of advice is not to worry about what other people think of your voice, your perception of the situation will always be worse than it really is.

Christina Young Lancaster










In Memory of Tracy Brooks

As many of you already know, on April 6, 1994 Tracy Brooks passed away at the age of four. Tracy was originally diagnosed with RRP when she was about nine months of age. For more than a year she was fighting a desperate battle against papilloma that were progressively invading her lungs.
She is survived by her mother Mary.