Life Raft patients share responses, side effects

By Norman Scherzer
Life Raft Group Coordinator
with Janet Hendrickson
Life Raft Group Medical Librarian

In the Life Raft Group’s February Newsletter, we presented the first data showing the response of 16 GIST patient members to STI571 (Gleevec). We defined response as tumor shrinkage, and reported that 87.5 percent of this group responded to Gleevec, most very quickly.

This month we report on the Gleevec response results of 58 Life Raft GIST patients on the trials for at least two months.

We reiterate our standard caveats — we are not professional researchers and any data collected by the Life Raft Group may not be representative of the clinical trials as a whole. Patientbased reporting and analysis is in its infant stages and may not always be accurate. Finally, these are relatively small numbers and small changes can have a disproportionate statistical effect.

The Life Raft Group data is based upon medical updates from 58 of the 60 evaluable member patients on the various Gleevec trials. Two member patients did not submit medical updates in time for this report. The table on Page 2 summarizes the Life Raft Group results. Seventy-one percent of the group demonstrated tumor shrinkage, with no differences amongst the three drug dosage groups — 400 mg/day, 600 mg/day, and 800 mg/day. Seven percent of patients reported their cancer had progressed, and they were taken off the trial. Seventeen percent remained stable with no change in tumor size. Of the 41 patients reporting shrinkage, one is receiving Gleevec on a compassionate use basis (the only non-trial member included in our data). The three patients with mixed responses are an important exception to the more common response patterns and demonstrate the effect of dose change in selected cases. Two patients initially experienced tumor growth that was subsequently reversed by higher doses (from 400 mg/day to 600 mg/day). One patient experienced the reverse — tumor growth following a dose reduction, caused by side effects, from 600 mg/day to 400 mg/day.

Side Effects

We had hoped to compare the side effect data presented at the recent conference of the American Society of Clinical Oncology (ASCO) with our own, but were unable to do so because of the difference in focus. The ASCO data focuses on high grade toxicity from the perspective of whether patients could stay on the trial and at what maximum dosage level. The Life Raft Group data, on the other hand, focuses upon a patient ranking of side effects by severity, using a scale of severe ( or high), medium and low.

In the April newsletter we noted that 34 trial participants reported 78 occurrences of side effects, with 32 percent of the total group ranking one or more as severe. Although we found, as anticipated, that the 600 mg/day group ranked their side effects as severe more frequently than did the 400 mg/ day group (54 percent versus 19 percent), we were surprised to find that gender was as significant as dosage in predicting severity of side effects, with 47 percent of all females reporting one or more severe side effects as compared to only 18 percent of males. Various skin problems (some which we now believe to be neurological) dominated the female severe side effect list.

In a subsequent newsletter we will revisit this side effect issue and present an updated analysis. We can report now, however, based upon this earlier survey, and upon subsequent online discussions at the Life Raft Group Internet-based chat site and at small group meetings of members and loved ones, that the management of side effects is a much more serious issue from the patient’s perspective than some other reports indicate.

Some of this is due to the quite natural shift in focus of GIST patients transitioning from the euphoria of surviving what had been a certain terminal disease to the very real prospect of having to take Gleevec, and cope with the management of its side effects, for the rest of their lives.

Some of this is also due to a more realistic assessment of the scope, frequency and severity of side effects when viewed solely from the quality of life concerns of the patient and caregiver than from the clinical trial concerns of the cancer researcher, whose traditional focus has been more on drug responsiveness and toxicity levels determined by the highest dosage that the patient could tolerate.

Finally, a great deal of this is the result of a clinical trial system which fails to adequately measure, evaluate and communicate side effects in a timely and consistent manner amongst clinical trial centers and to provide for adequate specialist support for their management.

For example, we were surprised to learn that in the GIST/Gleevec trials, there is no system for the routine sharing of information gained about side effects between trial centers, particularly between the Phase II and Phase III locations.