Bortezomib is active in patients with untreated or relapsed Waldenstrom's macroglobulinemia: a phase II study of the National Cancer Institute of Canada Clinical Trials Group.

Abstract

PURPOSE:

To evaluate the efficacy and toxicity of single-agent bortezomib in Waldenström's macroglobulinemia (WM).

PATIENTS AND METHODS:

Symptomatic WM patients, untreated or previously treated, received bortezomib 1.3 mg/m2 intravenously days 1, 4, 8, and 11 on a 21-day cycle until two cycles past complete response (CR), stable disease (SD) attained, progression (PD), or unacceptable toxicity. Responses were based on both paraprotein levels and bidimensional disease measurements.

RESULTS:

Twenty-seven patients were enrolled. A median of six cycles (range, two to 39) of bortezomib were administered. Twenty-one patients had a decrease in immunoglobulin M (IgM) of at least 25%, with 12 patients (44%) reaching at least 50% IgM reduction. Using both IgM and bidimensional criteria, responses included seven partial responses (PRs; 26%), 19 SDs (70%), and one PD (4%). Total response rate was 26%. IgM reductions were prompt, with nodal responses lagging. Hemoglobin levels increased by at least 10 g/L in 18 patients (66%). Most nonhematologic toxicities were grade 1 to 2, but 20 patients (74%) developed new or worsening peripheral neuropathy (five patients with grade 3, no grade 4), a common cause for dose reduction. Onset of neuropathy was within two to four cycles and reversible in the majority. Hematologic toxicities included grade 3 to 4 thrombocytopenia in eight patients (29.6%) and neutropenia in five (19%). Toxicity led to treatment discontinuation in 12 patients (44%), most commonly because of neuropathy.

CONCLUSION:

Bortezomib has efficacy in WM, but neurotoxicity can be dose limiting. The slower response in nodal disease may require prolonged therapy, perhaps with a less intensive dosing schedule to avoid early discontinuation because of toxicity. Future studies of bortezomib in combination with other agents are warranted.

• Authors: Christine I Chen, C Tom Kouroukis, Darrell White, Michael Voralia, Edward Stadtmauer, A Keith Stewart, John J Wright, Jean Powers, Wendy Walsh, Elizabeth Eisenhauer, National Cancer Institute of Canada Clinical Trials Group
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 25 Issue 12 Pg. 1570-5 (Apr 20 2007) ISSN: 1527-7755 [Electronic] United States
• PMID: 17353550 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Boronic Acids
• Protease Inhibitors
• Pyrazines
• Bortezomib

Topics

• Aged
• Aged, 80 and over
• Ambulatory Care
• Boronic Acids (adverse effects, therapeutic use)
• Bortezomib
• Canada
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Humans
• Infusions, Intravenous
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Recurrence, Local (diagnosis, drug therapy, mortality)
• Probability
• Protease Inhibitors (adverse effects, therapeutic use)
• Pyrazines (adverse effects, therapeutic use)
• Risk Assessment
• Salvage Therapy
• Severity of Illness Index
• Survival Rate
• Treatment Outcome
• Waldenstrom Macroglobulinemia (diagnosis, drug therapy, mortality)