Initial phase I clinical and pharmacokinetic assessment of G4544, an oral gallium-containing compound

8592 Background: An intravenous dose of gallium nitrate (54.5–81.7 mg/m2/day gallium for 5–7 days) is effective treatment for patients (pts) with cancer-related hypercalcemia. Preliminary studies showed consistent anticancer activity in pts with non-Hodgkin’s lymphoma (NHL). Low gallium doses by subcutaneous (SC) injection significantly reduced metabolic markers of disordered bone turnover in Paget’s disease. A multi-year multiple myeloma study showed significantly reduced bone loss in pts receiving chemotherapy and was possibly associated with increased survival when low doses of gallium were administered SC. In preclinical studies, gallium potently inhibited osteoclast-mediated bone resorption and may have anabolic effects on bone formation. Gallium-containing compounds such as gallium nitrate have low oral bioavailability. We investigated oral absorption of gallium-containing compounds and developed G4544. G4544 showed increased oral gallium absorption (2.2-fold increase in AUC and 2.8-fold increase in...