Abstract
The first in class proteasome inhibitor bortezomib (B) received its initial regulatory approval for therapy of patients with multiple myeloma (MM) in the relapsed/refractory setting. Modulation of proteasome function, however, is also a rational strategy for chemosensitization, and a variety of agents have shown synergistic activity with bortezomib pre-clinically, including anthracyclines. This formed the basis for evaluation of a regimen of bortezomib with pegylated liposomal doxorubicin (PLD). PLD+B, in a phase I study, induced a predictable and manageable toxicity pro. le, and showed encouraging anti-MM activity. In a recent international, randomized phase III trial, PLD+B demonstrated a superior overall response rate and response quality compared to bortezomib alone, as well as a longer time to progression, duration of response, progression-free survival, and overall survival. Sub-analyses revealed bene. ts in almost all clinically relevant subgroups, including several which would be considered to have high-risk disease. These findings have led to the establishment of the PLD+B regimen as one of the standards of care for patients with relapsed and/or refractory myeloma. Efforts are now underway to build on this combination further by adding other active anti-myeloma agents. In this review, we will discuss the role of PLD+B as an important addition to our therapeutic armamentarium for patients with MM.
Original language | English (US) |
---|---|
Pages (from-to) | 151-159 |
Number of pages | 9 |
Journal | Therapeutics and Clinical Risk Management |
Volume | 5 |
Issue number | 1 |
State | Published - 2009 |
Keywords
- Bortezomib
- Doxil®
- Multiple myeloma
- Pegylated liposomal doxorubicin
- Relapsed/refractory
- Velcade®
ASJC Scopus subject areas
- Safety Research
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmacology (medical)
- Chemical Health and Safety