A survival paradigm for GIST
By Norman Scherzer Executive Director, Life Raft Group
Almost every day the Life Raft Group office gets calls from GIST patients and doctors asking for information. Most are seeking ways to stay alive, or keep patients alive. As the research on GIST grows, including the critical research that the Life Raft Group conducts itself, a paradigm for survival is evolving for patients on Gleevec with inoperable tumors.
A few weeks ago European researchers * released their latest report about dosage and resistance. They reported that larger doses are related to longer times to disease progression.
In November the Life Raft Group will present a research paper to the Connective Tissue Oncology Society on relapse rates amongst metastatic GIST patients who initially responded to Gleevec. This data will show that higher doses are related to lower relapse rates.
Some researchers may take the position that patients should continue on lower doses (400 mg.) until all research has determined that this is unwise. (U.S. studies are ongoing and have not found any relationship between dosage and resistance.) We understand this but prefer to operate on the side of caution and see patients on a greater dosage until research proves it is safe to do otherwise.
Accordingly we
offer our survival paradigm for GIST
patients with inoperable tumors who are
on Gleevec:
• Start patients at 400 mg. per day.
There is no difference in initial
response to Gleevec related to dosage
levels. Instead, initial response seems
to be related to the type of mutation.
Side effects are often minimized by
starting on a lower doses and phasing in
higher doses.
• Gradually
increase the dosage to at least to 600
mg. per day, perhaps higher.**
Higher doses are related to lower
resistance rates.
Higher doses can prevent resistance
from subsequently occurring in
metastatic GIST patients who had initial
shrinkage.
This finding is consistent with the
recent European report on progression
and with earlier data from Europe
suggesting that clearance of Gleevec —
the rate at which the drug leaves the
body — increases over time. This may
explain why side effects get better over
time.
Current research has shown that
increasing dosage after resistance is
generally not successful in reversing
resistance, though it does help some
patients by halting disease progression.
Therefore, it is easier to prevent
the development of resistance with
higher doses than to try to reverse
resistance with higher doses after the
fact.
• Exercise caution
before reducing dosage in response to
side effects. Side effects are
related to dosage levels.
They usually get better over time.
•The development of resistance does not seem to slow over time — at least not so far — so patients at lower doses should not find false comfort in the fact that they have not yet developed resistance.
This is not a perfect blueprint and others may disagree. This paradigm is based on what we have learned from the research community, our own research and from more than 500 Life Raft Group case records. Be warned, however, that we are not physicians and we urge patients to use this information only as the basis for an informed discussion with their own doctors.
Also, these remarks pertain only to GIST patients on Gleevec with tumors that are not amenable to surgery. Patients with operable tumors should talk to their physicians about surgery.
We do not have enough data yet regarding the efficacy of Gleevec — at any dose — in patients who have had surgery and are taking Gleevec on a preventive (adjuvant) basis.
* European Organization for Research and the Treatment of Cancer (EORTC), the Italian Sarcoma Group (IRG) and Australasian Gastrointestinal Trials Group (AGITG).
** The European study compared 400 mg. to 800 mg. and concluded that the higher dose had a longer rate to progression. They did not look at 600 mg. The Life Raft Group has compared 400 mg. to 600 mg. and more; we did not have enough data to distinguish between 600mg and 800 mg.
