Faculty Collaboration Database

Age-stratified phase I trial of a combination of bortezomib, gemcitabine, and liposomal doxorubicin in patients with advanced malignancies. Cancer Chemother Pharmacol 2012 May;69(5):1117-26

Date

12/30/2011

Pubmed ID

22205203

Pubmed Central ID

PMC4091047

DOI

10.1007/s00280-011-1808-4

Scopus ID

2-s2.0-84862281935 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

BACKGROUND: 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/m(2) (days 1 and 8), gemcitabine 500 mg/m(2) (days 1 and 8), and liposomal doxorubicin 20 mg/m(2) (day 1).

RESULTS: In the < 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 ≥ 65-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).

CONCLUSION: 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.

Author List

Falchook GS, Duvic M, Hong DS, Wheler J, Naing A, Lim J, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Age Factors
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Boronic Acids
Bortezomib
Child
Child, Preschool
Deoxycytidine
Dose-Response Relationship, Drug
Doxorubicin
Drug Synergism
Female
Humans
Male
Middle Aged
Neoplasms
Pyrazines
Treatment Outcome
Young Adult