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.
J Clin Oncol. 2007 Mar 12
Chen CI, Kouroukis CT, White D, Voralia M, Stadtmauer E, Stewart AK, Wright JJ, Powers J, Walsh W, Eisenhauer E.
Princess Margaret Hospital, Toronto; Juravinski Cancer Centre, Hamilton; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia; Saskatoon Cancer Centre, Saskatoon, Saskatchewan, Canada; Eastern Cooperative Oncology Group, Philadelphia, PA; Cancer Therapy Evaluation Program, National Cancer Institute, National Institute of Health, Bethesda, MD.
PURPOSE: To evaluate the efficacy and toxicity of single-agent bortezomib in Waldenstrom's macroglobulinemia (WM).
PATIENTS AND METHODS: Symptomatic WM patients, untreated or previously treated, received bortezomib 1.3 mg/m(2) 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. |
