STI571 notes from leukemia group at OHSU

Editor's note: The following comes from Life Rafter Trudy W., who attended the February and March meetings of the CML (chronic myelogenous leukemia) group at Oregon Health Sciences University in Portland. These leukemia patients have had a lot of experience with STI571, as some have been on their clinical trial for as long as two years.

The annual meeting of the American Society of Clinical Oncologists takes place May 12-15 at Moscone Center, San Francisco. Dr. Charles Blanke of OHSU has been asked to present results to date of the Novartis-sponsored Phase II GIST trial. We will look forward to information following this conference!

Adds LRG Coordinator Norman Scherzer: What is particularly noteworthy about the presentation will be that it will likely be made to the plenary session. This is highly unusual for a phase II study, but the early results are so striking that our trial will be the major news of the conference.

Dr. Michael Mauro of the CML staff emphasized how important it is for everyone to keep up with good general health maintenance. CML and GIST patients have focused so much on trying to survive, many may have forgotten or ignored the need to maintain routine annual checkups. With many in attendance who might not have been there without STI571, it was a good reminder that life is continuing and we need to do all we can to improve and maintain the quality of life we are experiencing.

Lora Wilson, the clinical trial nurse for the GIST trial at OHSU, was guest speaker at the March meeting. She told the CML patients that GIST stands for gastrointestinal stromal tumor and is a soft-tissue cancer which produces tumors in the abdomen. The characteristics that set GIST apart from other leiomyosarcomas are significant and still being studied.

The first trial for treatment of GIST with STI571 was opened at Oregon Health Sciences University in Portland, Fox Chase in Philadelphia, Dana Farber in Boston, and the University of Helsinki in Finland with a total of 36 patients. This trial was sponsored by the maker of STI571, Norvartis, which is marketing the drug as Glivec. It has since been expanded to 142 openings. A new Phase III trial sponsored by the National Cancer Institute has begun and is expected to serve an additional 600 GIST patients within 24 months. Both trials are virtually identical, with the major difference being drug dosages. The earlier trial is comparing 400 mg and 600 mg dosages, while the new phase III trial is comparing 400 and 800 mg doses. (Note: Neither trial has a control group receiving another treatment or a placebo, as there is no other effective treatment for GIST and using a placebo would be both unwarranted and unethical.)

The benefits reported to date include decreases in tumor size, reduced need for pain medication and improved endurance. To Wilson’s knowledge, though some patients at OHSU have had to stop taking the drug temporarily, no one has been removed from the trial due to low blood counts.

Since there is no marker in the blood for GIST as there is for CML, tumor tissue is tested to determine if it expresses a protein (oncogene) called ckit which regulates the enzyme tyrosine kinase. STI-571 works to inhibit this enzyme, thereby stopping the growth of tumor cells. Where CML patients are monitored through bone marrow biopsies, GIST patients are primarily monitored with CT scans which show changes in tumor mass.

Research has found other cancers that express c-kit including some brain tumors, small cell lung cancer and prostate cancer. Discussion is taking place about the possibility of a trial open to other cancer patients with tumors expressing c-kit.

There was discussion among the patients present about the use of vitamins with STI-571. Several said they take their supplements at the same time as STI-571 and have not had any adverse reaction. Others take their supplements at a different meal than they take STI- 571. Wilson said as far as they know, basic multiple vitamins (but no megadoses) do not interfere with the assimilation of STI-571.

Adds Scherzer: The Life Raft Group is completing its own study on side effects and will report on the results in the next newsletter. A preliminary review of the still-incomplete data is revealing that the worst side effects seem to be skin problems, cramping, eye puffiness and reflux. There appears to be a pattern emerging, with those on the greater 600 mg dose reporting a greater degree in the severity of side effects. There also seems to be some early evidence that the gender of the patient plays a role in side effects.