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Am J Clin Oncol. 2011 Dec;34(6):597-602. doi: 10.1097/COC.0b013e3181f9441f.

Phase 1 trial of gemcitabine with bortezomib in elderly patients with advanced solid tumors.

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  • 1Department of Medicine, Division of Hematology, Oncology and Transplantation, Comprehensive Cancer Center, University of Minnesota, Minneapolis, USA.

Abstract

INTRODUCTION:

Bortezomib, a proteasome inhibitor, has synergistic antitumor activity with gemcitabine, an antimetabolite, in preclinical and clinical studies. The safety of this combination has not yet been established in elderly patients; therefore, this dose-escalation study was designed to assess the maximum-tolerated dose of bortezomib and gemcitabine in patients aged 70 years or older with advanced-stage solid tumors.

PATIENTS AND METHODS:

Gemcitabine was administered intravenously (800 to 1000 mg/m) over 30 minutes on days 1 and 8, followed 60 minutes later by bortezomib administered as an intravenous push over 3 to 5 seconds (1.0 to 1.8 mg/m) on a 21-day cycle. This study used a standard phase 1 dose-escalation design with 3 or 6 patients per dose level.

RESULTS:

Seventeen patients with stage IV solid tumors were treated. Median age was 73 years (range: 70 to 87 y). All patients had an Eastern Cooperative Oncology Group (ECOG) performance status less than 2. Median number of earlier chemotherapy regimens was 2 (range: 0 to 6). Dose-limiting toxicities were seen in 2 of 8 patients enrolled at the second dose level of gemcitabine (1000 mg/m) and bortezomib (1.0 mg/m), which consisted of grade ≥3 lower extremity edema, thrombocytopenia, fatigue, and dehydration. The most common grade ≥3 toxicities included thrombocytopenia (n=9), neutropenia (n=6), and anemia (n=5). Partial response (n=3) or disease stabilization (n=3) was seen in 6 of 14 evaluable patients.

CONCLUSIONS:

Concurrent weekly gemcitabine (800 mg/m) and bortezomib (1 mg/m) is the recommended schedule for future phase 2 trials in elderly patients with stage IV solid tumors.

PMID:
21127410
[PubMed - indexed for MEDLINE]
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