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

Authors


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/m2) and vincristine (1.4 mg/m2; 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/m2 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. Cancer 2006. © 2006 American Cancer Society.

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