, Volume 69, Issue 5, pp 1117-1126
Date: 29 Dec 2011

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

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Preclinical data suggest synergistic activity of bortezomib, gemcitabine, and liposomal doxorubicin. Because tolerance to therapy may be attenuated in elderly patients, we performed an age-stratified phase I trial of this combination.

Patients and methods

Two parallel age-stratified arms (<65 and ≥65 years old) were accrued (3 + 3 design). Starting doses included 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).


In the <65-year-old group, 65 patients were treated; the maximum-tolerated dose was bortezomib 1.3 mg/m2, gemcitabine 800 mg/m2, and liposomal doxorubicin 35 mg/m2. In the ≥65-year-old group, 28 patients were treated; the recommended phase II dose was bortezomib 1.0 mg/m2, gemcitabine 800 mg/m2, and liposomal doxorubicin 20 mg/m2. Dose-limiting toxicities included thrombocytopenia and neutropenia. The most common toxicities were mild cytopenias, fatigue, and neuropathy. Ten patients achieved partial responses (6 of 7 patients with cutaneous T-cell lymphoma; 4 of 16 patients with small cell carcinomas, including lung, prostate, ovarian, and nasopharyngeal).


Combination of bortezomib, gemcitabine, and liposomal doxorubicin is well tolerated, but with a lower recommended phase II dose in elderly patients, and demonstrated antitumor activity, especially in T-cell and small cell histology malignancies.

Prior presentation of results: American Society of Clinical Oncology Annual Meeting 2007, poster presentation.