Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression.

Abstract

PURPOSE:

This phase III international study compared the efficacy and safety of a combination of pegylated liposomal doxorubicin (PLD) plus bortezomib with bortezomib monotherapy in patients with relapsed or refractory multiple myeloma.

PATIENTS AND METHODS:

Six hundred forty-six patients were randomly assigned to receive either intravenous bortezomib 1.3 mg/m(2) on days 1, 4, 8, and 11 of an every 21-days cycle, or the same bortezomib regimen with PLD 30 mg/m(2) on day 4.

RESULTS:

Median time to progression was increased from 6.5 months for bortezomib to 9.3 months with the PLD + bortezomib combination (P = .000004; hazard ratio, 1.82 [monotherapy v combination therapy]; 95% CI, 1.41 to 2.35). The 15-month survival rate for PLD + bortezomib was 76% compared with 65% for bortezomib alone (P = .03). The complete plus partial response rate was 41% for bortezomib and 44% for PLD + bortezomib, a difference that was not statistically significant. Median duration of response was increased from 7.0 to 10.2 months (P = .0008) with PLD + bortezomib. Grade 3/4 adverse events were more frequent in the combination group (80% v 64%), with safety profiles consistent with the known toxicities of the two agents. An increased incidence in the combination group was seen of grade 3/4 neutropenia, thrombocytopenia, asthenia, fatigue, diarrhea, and hand-foot syndrome.

CONCLUSION:

PLD with bortezomib is superior to bortezomib monotherapy for the treatment of patients with relapsed or refractory multiple myeloma. The combination therapy is associated with a higher incidence of grade 3/4 myelosuppression, constitutional symptoms, and GI and dermatologic toxicities.

• Authors: Robert Z Orlowski, Arnon Nagler, Pieter Sonneveld, Joan Bladé, Roman Hajek, Andrew Spencer, Jesús San Miguel, Tadeusz Robak, Anna Dmoszynska, Noemi Horvath, Ivan Spicka, Heather J Sutherland, Alexander N Suvorov, Sen H Zhuang, Trilok Parekh, Liang Xiu, Zhilong Yuan, Wayne Rackoff, Jean-Luc Harousseau
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 25 Issue 25 Pg. 3892-901 (Sep 01 2007) ISSN: 1527-7755 [Electronic] United States
• PMID: 17679727 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Boronic Acids
• Pyrazines
• liposomal doxorubicin
• Polyethylene Glycols
• Bortezomib
• Doxorubicin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Boronic Acids (administration & dosage)
• Bortezomib
• Cardiovascular Diseases (chemically induced, epidemiology)
• Disease Progression
• Disease-Free Survival
• Doxorubicin (administration & dosage, analogs & derivatives)
• Drug Resistance, Neoplasm
• Female
• Hematologic Diseases (chemically induced)
• Humans
• Incidence
• Male
• Middle Aged
• Multiple Myeloma (drug therapy)
• Neoplasm Recurrence, Local
• Polyethylene Glycols (administration & dosage)
• Pyrazines (administration & dosage)