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

作者：Falchook G S^*; Duvic M; Hong D S; Wheler J; Naing A; Lim J; Kurzrock R

来源：Cancer Chemotherapy and Pharmacology, 2012, 69(5): 1117-1126.

DOI：10.1007/s00280-011-1808-4

• Bortezomib
• Gemcitabine
• Liposomal doxorubicin
• Cutaneous T-cell lymphoma
• Small cell carcinoma
• Phase I

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. %26lt;br%26gt;Two parallel age-stratified arms (%26lt; 65 and a parts per thousand yen65 years old) were accrued (3 + 3 design). Starting doses included bortezomib 0.7 mg/m(2) (days 1 and 8), gemcitabine 500 mg/m(2) (days 1 and 8), and liposomal doxorubicin 20 mg/m(2) (day 1). %26lt;br%26gt;In the %26lt; 65-year-old group, 65 patients were treated; the maximum-tolerated dose was bortezomib 1.3 mg/m(2), gemcitabine 800 mg/m(2), and liposomal doxorubicin 35 mg/m(2). In the a parts per thousand yen65-year-old group, 28 patients were treated; the recommended phase II dose was bortezomib 1.0 mg/m(2), gemcitabine 800 mg/m(2), and liposomal doxorubicin 20 mg/m(2). 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). %26lt;br%26gt;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.

• 出版日期2012-5