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

 -  Patients with CML in chronic phase, accelerated phase based on cytogenetic
 abnormalities in addition to Philadelphia chromosome but with less than 5 % blasts, or
 GIST taking imatinib

 -  Patients with life expectancy of at least 12 months; patients must be on imatinib at
 time of study entry.

 -  Ability to sign informed consent and/or assent

 Exclusion Criteria:

 -  Patients with a known parathyroid disorder; active thyroid disorder except stable,
 replaced hypothyroidism; Cushing's syndrome; uncontrolled diabetes mellitus (could
 have unexpected fluid, electrolyte and mineral shifts); sarcoidosis (elevated
 calcitriol levels from granulomata); hypercalcemia of malignancy (i.e., PTHrP-mediated
 or extensive bone mets);known tumor-induced osteomalacia; Paget's disease of bone;
 known X-linged or autosomal dominant hypophosphatemic rickets/osteomalacia; known
 renal tubular disease (e.g., Fanconi's syndrome); chronic GI malabsorption sydrome.

 -  Patients taking oral calcium in excess of calcium 750 mg and Vitamin D 400 mg daily
 (ie, that contained in a single multivitamin). Patients taking more than these amounts
 may be eligible for this study if vitamin and mineral supplementation in excess of
 this is stopped for a minimum of 2 weeks prior to study entry.

 -  Patients taking oral or intravenous steroids, calcitonin, any selective estrogen
 modulating agent such as tamoxifen or raloxifene, gallium nitrate, and other bone
 seeking radionuceotides, any calcimimetic agent such as cinacalet.

 -  Patients who have had prior treatment with cisplatin, carboplatin, oxaliplatin,
 ifosfamide, or cyclophosphamide.