Glivec at higher doses combats progression

Largest study of GIST finds 800 mg. keeps cancer at bay longer

BASEL, Switzerland – Clinical trial patients taking an 800 mg. daily dose of Glivec for treatment of gastrointestinal stromal tumor (GIST) had significantly longer progression- free survival compared to the patients taking the standard 400 mg. daily dose, according to results published Sept. 24 in The Lancet.

The results showed that doubling the daily dose of Glivec (imatinib, or Gleevec in the U.S) may improve progression-free survival of patients with KIT (CD117)-positive GIST that is inoperable and/or has spread. At a median follow-up of 760 days, patients receiving 800 mg. per day experienced five months longer progression- free survival compared to patients on 400 mg. a day.

“The introduction of Glivec has dramatically improved the prognosis of patients diagnosed with advanced KIT-positive GIST,” said Jaap Verweij, head of the Division of Experimental Chemotherapy, Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands, the principal investigator and lead author of this publication.

“While further research is needed to establish the impact of a higher starting dose on patients’ survival, the prolonged progressionfree survival seen in this study represents benefit to patients.”

The international, randomized, phase III study was conducted by the EORTC (European Organization for Research and Treatment of Cancer), ISG (Italian Sarcoma Group) and the AGITG (Australasian Gastrointestinal Trials Group). A total of 946 patients with advanced and/ or metastatic KIT-positive GIST received either 400 or 800 mg. of Glivec per day. Patients who experienced any disease progression on 400 mg. were allowed to increase to 800 mg. to regain control of the disease. At the time of the analysis (May 2004), a total of 412 patients had completed treatment in the trial, which had progression-free survival as the primary endpoint.

Patient treatment with 800 mg. of Glivec per day significantly increased progression-free survival compared to treatment with 400 mg. per day. Although side effects were more common and more severe with the higher dose, the majority of patients did not require a dose reduction. Treatment in both groups was fairly welltolerated.

The most common undesirable side effects of Glivec treatment are: headache, nausea, vomiting, diarrhea, dyspepsia, myalgia, muscle spasm and cramps, joint swelling, dermatitis, eczema, rash, edema, fluid retention, neutropenia, thrombocytopenia or anemia.

GIST is the most frequent form of gastrointestinal cancer, a lifethreatening disease highly resistant to traditional chemotherapy and radiation. Surgery is considered the best way to initially treat GIST. However, many GISTs cannot be surgically removed because they are too large or have already spread to other parts of the body before diagnosis.

When surgery is performed, cells from the original GIST may remain behind or the cancer may return in another site. Experts believe that GIST may be more prevalent than previously believed, affecting approximately 15 people per 1 million per year.