Abstract | PURPOSE: 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.
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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)
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Chemical References |
- Boronic Acids
- Protease Inhibitors
- Pyrazines
- Bortezomib
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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)
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