Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma: a Phase III multicenter randomized trial.

Abstract

BACKGROUND:

Pegylated liposomal doxorubicin has pharmacologic and safety advantages over conventional doxorubicin.

METHODS:

For this noninferiority trial, 192 patients with newly diagnosed, active multiple myeloma were randomized to receive either combined pegylated liposomal doxorubicin (40 mg/m(2)) and vincristine (1.4 mg/m(2); maximum, 2.0 mg) as an intravenous infusion on Day 1 plus reduced-dose dexamethasone (40 mg) orally on Days 1-4 (DVd) (n = 97 patients) or combined vincristine (0.4 mg per day) and conventional doxorubicin (9 mg/m(2) per day) as a continuous intravenous infusion on Days 1-4 plus reduced-dose dexamethasone (VAd) (n = 95 patients) for at least 4 cycles. Treatment was repeated every 4 weeks until patients either achieved maximal response, disease progression, or unacceptable toxicity or underwent transplantation. The primary endpoints were response and toxicity.

RESULTS:

Objective response rates (DVd, 44%; VAd, 41%), progression-free survival (hazard ratio, 1.11; P = 0.69), and overall survival (hazard ratio, 0.88; P = 0.67) were similar between the treatment groups. However, DVd was associated with significantly less Grade 3/4 neutropenia or neutropenic fever (10% vs. 24%; P = 0.01), a lower incidence of sepsis, and less antibiotic use. Compared with VAd, DVd also significantly decreased the need for central venous access (P < 0.0001) and growth-factor support (P = 0.03) and resulted in less alopecia (20% vs. 44%; P < 0.001) but more hand-foot syndrome (25% vs. 1%; P < 0.001), mainly Grade 1/2.

CONCLUSIONS:

The DVd regimen demonstrated similar efficacy with less toxicity and supportive care compared with VAd, which should improve clinical utility and optimize the opportunity for transplantation.

• Authors: Robert M Rifkin, Stephanie A Gregory, Ann Mohrbacher, Mohamad A Hussein
• Journal: Cancer (Cancer) Vol. 106 Issue 4 Pg. 848-58 (Feb 15 2006) ISSN: 0008-543X [Print] United States
• PMID: 16404741 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2006 American Cancer Society.

Chemical References

• liposomal doxorubicin
• Polyethylene Glycols
• Vincristine
• Dexamethasone
• Doxorubicin

Topics

• Administration, Oral
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Catheterization, Central Venous
• Dexamethasone (administration & dosage)
• Doxorubicin (administration & dosage, adverse effects, analogs & derivatives)
• Female
• Fever (chemically induced)
• Humans
• Infusions, Intravenous
• Male
• Middle Aged
• Multiple Myeloma (drug therapy, pathology)
• Neutropenia (chemically induced)
• Polyethylene Glycols (administration & dosage, adverse effects)
• Survival Analysis
• Treatment Outcome
• Vincristine (administration & dosage)