Doctors hear of Life Raft experience at London meet
More than 400 physicians attend symposium on Glivec therapy for GIST
The Life Raft Group’s profile in Europe skyrocketed this month when Executive Director Norman Scherzer spoke to more than 400 physicians from 32 countries at a three-day symposium, “Glivec: First Successful Systemic Treatment for GIST.”
The event was held Sept. 18-20 at the Hotel Intercontinental in London to further the understanding of changes in the management of patients with GIST in the era of Glivec.
Scherzer was the wrap-up speaker at the symposium’s first day with a presentation titled “Medicine on the Internet: Impact on Physician- Patient Relationships, the Experience of the Life Raft Group.”
Here are excerpts from Scherzer’s report which he filed Sept. 22. He cautions: “This is written to the best of my ability from my notes, and my recollections, while flying back from London. It is always possible that human error may be present, and I would ask you to treat my comments accordingly.”
“I was overwhelmed by the response to my presentation at the London GIST conference and by the acceptance both of my remarks and of the Life Raft Group,” Scherzer said. “Imagine my surprise when the opening and keynote speaker, Dr. Gordon McVie of the United Kingdom — whom I had never met before — remarked how delighted he was to have the Life Raft Group represented and how important he felt that we were to the proceedings.”
Given to all attendees was an abstract of his remarks and a paper, “Introducing the Life Raft Group,” which read:
“The Life Raft Group is an international, Internet-based, nonprofit organization providing support to patients with GIST through education and innovative research.
“The paradigm for doctor-patient relationships is changing, and the challenge is how to shape these changes to benefit both doctors and patients. These relationships have been affected recently by managed care and by patient access to data on the Internet. This presentation reports on the evolution of a movement from patients accessing data on the Internet to patients creating data and then sharing it with others via the Internet.
“Within six months of the beginning of the Glivic (STI571) clinical trials in GIST, the headline, ‘Initial Survey Shows High Response Rate’ — appearing in the Life Raft Group’s monthly newsletter — introduced the first Internet-based report of drug response. Subsequent newsletters reported on the role of gender in side effects, continued to track rates of response to Glivec, and provided a comprehensive survey of side effects from the patient’s perspective. The result has been to turn the flow of clinical data upside down, with the patient now receiving information first.
“Patient
perspective data have introduced a
complementary way of looking at side
effects, based on a unique measurement
scale developed for patients, as opposed
to the more traditional toxicity scales
of the U.S. National Cancer Institute
and cancer agencies in other countries.
Data on the quality of medical care and
the accuracy of patient reporting in
clinical trials are also presented, with
a clear correlation demonstrated between
them.”
Tidbits Scherzer
gleaned at the conference:
• Although gastrointestinal stromal
tumor is a rare disease, and although no
one actually knows how prevalent it is,
the growing consensus is that it is more
common than originally thought. Medical
professionals guesstimate the annual
incidence rate at 20 per million people,
with an almost equal distribution of men
and women, and with a median age in the
60s.
• Primary tumors are most likely to
occur in the stomach (50+ percent),
followed by the small intestine (30+
percent), followed by the colon/rectum
(less than 10 percent).
• The history of the diagnosis of GIST
is very recent, with the Japanese
credited with finding c-kit in GIST in
1998 — the forerunner of c-kit testing
which got underway, on a small scale, in
clinical practice in early 2000. Prior
to c-kit testing, the most common
misdiagnosis of GIST was leiomyosarcoma,
followed by leiomyoblastoma.
• Prognosis for recurrence: There was a
consensus that the best predictors for
the recurrence of GIST, following
initial surgery, are tumor size and
mitotic rate, although it was noted that
GIST has a lower mitotic rate than other
soft tissue sarcomas. About 70 percent
of GIST displays spindled cells.
• About 95 percent or more are CD117
(c-kit) positive. That means that some
GIST tumors are c-kit negative, although
the diagnosis for GIST will continue to
depend upon a positive c-kit test as the
gold standard.
• Testing for c-kit is based upon using
commercially available antibodies. There
has been no systematic evaluation of the
quality of these antibodies. A paper was
presented comparing the reliability of
several of the most common. DAKO was
considered the best, followed closely by
Novocostra. Santa Cruz and Neomarkers
were considered much less reliable,
producing an unacceptable number of
false positives. What this all means is
that accurate c-kit testing depends upon
experienced pathologists using a
reliable commercial antigen.
• Dr. Stephan Dirnhoffer of the
University of Basel, Switzerland, in
collaboration with Dr. Chris Corless of
Oregon Health Sciences University, has
produced the first GIST micro array
(think of about 1,000 tissue samples on
a single slide).
• Treatment response and genetic
mutation: As reported at the May
conference of the American Society of
Clinical Oncology, there is a clear
correlation between genetic mutation and
response to Glivec, with mutation in
exon 11, having the best response. “What
I learned for the first time was that
exon 9 — which has a poorer response to
Glivec — has been found only in patients
with a primary tumor in the small bowel
or colon; and that exon 9 has not been
found in any patients with a primary
tumor in the stomach,” said Scherzer.
• There were no clear answers about the
value of Glivec pre- and post-surgery,
nor about the optimal dose, nor how long
patients should remain on the drug. Of
importance to many was the current
treatment protocol being used at
Dana-Farber Cancer Institute in Boston:
Start patients at 400 mg per day,
increasing to 600 mg per day as
indicated.
There are a number of new trials for GIST patients using Glivec, with some at the meeting expressing concern that there may be too many for a relatively small number of patients. These trials include the neoadjuvant (before surgery) and adjuvant trials that Life Raft Group members have reported on, plus a new French trial run by the French sarcoma group.
Although the treatment with Glivec seems to be lasting for most, there is concern that remaining dormant cancer cells can produce recurrence with the cessation of treatment, and sometimes in the presence of treatment. The speculation is that this resistance to Glivec will grow over time.
The objective is to find ways to manage GIST in the interim and to find new treatments. There was a great deal of discussion, both in the formal sessions and in the many informal ones that followed, about the need for international collaboration to evaluate strategies for overcoming resistance, including working with the Life Raft Group whose daily discussions provide a sentinel system for reporting the incidence of resistance and any success in overcoming this.
There was also an emphasis on the need to obtain fresh tissue in such situations, particularly preand post-surgery. Once again the collaboration of the Life Raft Group, including the goal of creating a patient-driven tumor bank, was discussed.
“A developing consensus I walked away with was that patients who stop responding to Glivec should not be taken off the drug,” said Scherzer.
The consensus on how to take Glivec remains: Take Glivec with food, not because it is relevant to drug absorption, but because it may be helpful in avoiding certain gastric related side effects. Also, do not to take Glivec with grapefruit juice, because it may interfere with drug absorption.
Scherzer also met with about a dozen key clinicians and researchers outside the formal meeting to discuss collaborative efforts.
Also, Scherzer met with David Cook, United Kingdom Life Rafter, “who was kind enough to come down to London from Sheffield, England, to meet with me.”
Those with Microsoft Power Point software can get a copy of the slides Norman presented, and the Microsoft Word document, “Introducing the Life Raft Group,” by contacting him via e-mail at normanis@bellatlantic.net.
