Age-stratified phase I trial of a combination of bortezomib, gemcitabine, and liposomal doxorubicin in patients with advanced malignancies

14087 Background: Bortezomib, a potent proteasome and NF-kB inhibitor, potentiates the activity of chemotherapy in a variety of tumors in vitro and in mouse models, and preclinical data suggest that the combination of bortezomib, gemcitabine, and liposomal doxorubicin is synergistic. Because tolerance to combination therapy may be attenuated in elderly patients, we performed a phase I age- stratified trial to determine the maximum tolerated dose (MTD), toxicity, and antitumor activity of this combination. Methods: Starting doses were bortezomib 0.7 mg/m2 (days 1 and 8), gemcitabine 500 mg/m2 (days 1 and 8), and liposomal doxorubicin 20 mg/m2 (day 1). Two parallel age-stratified arms (< 65 and = 65 years old) were accrued, with at least three patients per dose level per arm. Each treatment cycle was 21 days. Results: 47 patients have enrolled, and the MTD has not yet been reached. For patients < 65 years old, accrual continues at the ninth dose level with bortezomib 1.3 mg/m2 (days 1, 4, 8, 11), gemcitabin...