Effect of Imatinib on Bone Metabolism in Patients With Chronic Myelogenous Leukemia or Gastrointestinal Stromal Tumors

Overview

The drug that you are taking for your cancer, imatinib (GleevecTM), has recently been shown to have some new types of side effects. In some people, imatinib can affect how bones are made. The purpose of this study is to find out if imatinib is causing these side effects in you. We can check how your bones form by testing your blood and urine. We can also check your bone strength by doing a special X-ray of your bone called bone density (or DEXA scan).

Preliminary data from this institution suggest that imatinib, likely by inhibiting platelet derived growth factor receptor (PDGFR), inhibits bone formation and resorption in a high percentage of patients with either chronic myelogenous leukemia (CML) or gastrointestinal stromal tumors(GIST).1 Some, but not all, patients taking imatinib developed hypophosphatemia but the effect on bone, as measured by markers of bone synthesis and metabolism, was seen in some patients with normal phosphate levels as well. Marked urinary phosphate wasting with elevated levels of parathyroid hormone was seen in nearly all patients. The effect of imatinib on bone may be dose-related. Patients with hypophosphatemia were routinely started on oral phosphate replacement, but follow up determinations of urinary phosphate wasting were not performed. The clinical consequences of these abnormalities on bone are not yet known. This trial will study 60 patients with CML in chronic phase, early accelerated phase (as detected by cytogenetics only) or GIST who are already taking imatinib. Parameters relating to bone metabolism will be checked every 3 months for 2 years. We will determine the incidence of bone abnormalities in this treated population, determine whether fasting serum phosphate can predict for changes in bone metabolism, determine whether there is change in bone density by measuring serial bone densitometry, determine whether oral phosphate replacement can restore phosphate balance, and determine whether there is a dose effect of imatinib on parameters of bone metabolism.