A multicenter phase II trial of 4′-Iodo-4′-deoxydoxorubicin (IDOX) in primary amyloidosis (AL)

Introduction. 4′-Iodo-4′-deoxydoxorubicin (IDOX) has been reported to bind to and lead to the catabolism of amyloid deposits. A multicenter study attempted to develop a dosing schedule to confirm those results. Methods. Patients with biopsy-proven amyloidosis were required to have a cardiac ejection fraction > 50%, ventricular septal thickness < 20 mm, serum creatinine < 2.5 mg per dL, bilirubin ≤ 2.0 mg per dL, neutrophils < 1,500 per μL, and platelets > 100,000 per μL. IDOX was administered intravenously over 1 hour at a dose of 15 mg per m² once a week for 4 consecutive weeks. This therapy was repeated every 3 months up to 4 times. Results. Twenty-five previously treated and 15 untreated patients with primary amyloidosis (AL) received therapy. Fifteen patients had > 3 g of protein per day in the urine. Eleven patients had an ejection fraction < 60%. One, 2, 3, 4, and 5 organ systems were involved in 22, 10, 4, 3, and 1 patient, respectively. The median time between diagnosis and initiation of IDOX was 17.4 months. There were 6 responses (15%). Twelve of the patients have died. Conclusion. IDOX administered in this protocol was insufficiently active at the current dose.