Bortezomib in the management of multiple myeloma

Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA.
Cancer Management and Research 09/2009; 1:107-17.
Source: PubMed

ABSTRACT Multiple myeloma (MM) is a B-cell malignancy characterized by clonal expansion of plasma cells within the bone marrow, the presence of a serum and/or urine monoclonal protein, lytic bone lesions, and anemia. On a cellular level, the disease is characterized by complex interactions between tumor cells and the surrounding bone marrow microenvironment. Understanding of the relationship between malignant plasma cells and the microenvironment has sparked ongoing efforts to develop targeted therapeutic agents for treatment of this disease. The successful development of the first-in-class small-molecule proteasome inhibitor bortezomib occurred as a result of these efforts. This review focuses on the rationale for bortezomib therapy in the treatment of patients with newly diagnosed and relapsed MM, important treatment-related side effects, and future directions for use of bortezomib and other, emerging proteasome inhibitors.

Download full-text


Available from: Irene M Ghobrial, Sep 26, 2015
26 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Intermittent, high-dose dexamethasone treatment was given to 49 consecutive patients with refractory multiple myeloma. In patients who were unresponsive to previous treatment, the response rate of 27% was similar to that achieved with the VAD regimen, which combines the same schedule of dexamethasone with vincristine and doxorubicin given by continuous infusion. Among patients with relapses, VAD chemotherapy induced remissions in 11 of 17 patients (65%), whereas dexamethasone alone induced remissions in 4 of 19 (21%). The median survival of all patients responding to either treatment, 22 months, was longer than that from any previous program for treatment of resistant myeloma. These findings indicate the value of frequent dexamethasone administration in patients unresponsive to standard therapy and show the major role of vincristine and doxorubicin given by continuous infusion in patients with relapses. They also suggest different mechanisms for primary and secondary resistance to chemotherapy.
    Annals of internal medicine 08/1986; 105(1):8-11. · 17.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A single-arm, phase II perspective clinical trial was done in a tertiary care setting to determine the efficacy of high-dose methylprednisolone in the treatment of patients with refractory or relapsed multiple myeloma. Twenty patients who had failed at least one chemotherapeutic regimen received methylprednisolone (2 g) intravenously three times weekly for 8 weeks. After 8 weeks, responders were placed on a maintenance phase of 2 g intravenously weekly with an 8-week reinduction at the time of relapse. Five patients died within the first month of therapy. There were two complete responses, two objective responses and three minor responses. The median survival for all 20 patients was 2.2 months. Median survival for the seven responders was 19 months, with a relapse-free survival of 15 months. Five patients survived at least 16 months. High-dose methylprednisolone is an easily administered, relatively nontoxic, and effective therapy in a subset of patients with multiple myeloma.
    Leukemia 01/1996; 9(12):2115-8. · 10.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A total of 142 patients with multiple myeloma received VAD as remission induction therapy. Seventy-five were previously untreated and 67 had relapsed (31) or refractory disease (36). Vincristine (total dose 1.6 mg) was infused with doxorubicin 36 mg m-2 by continuous ambulatory pump over 4 days. In addition, oral dexamethasone 40 mg day-1 was given for 4 days. Intermittent dexamethasone was only given to 19 patients. Courses were repeated every 21 days. The overall response rate was 84% [27% complete response (CR)] in previously untreated patients and 61% (3% CR) in patients with relapsed and refractory disease. The median survival was 36 months for untreated patients and 10 months for those who had received prior therapy. VAD was well tolerated; however, despite prophylaxis, 54% patients received antibiotics at some time during therapy and 37% had dyspepsia. Twenty-three patients subsequently received a transplant (eight allografts, eight marrow autografts and seven peripheral blood stem cell transplants). Eight have died-four in the allogeneic group and four in the autologous group. The overall median survival of transplanted patients has not yet been reached. VAD is an effective, out-patient therapy for inducing remission in multiple myeloma. Post-remission therapy needs to be optimised, but it is likely that the needs of previously untreated patients may be different from those with relapsed and refractory disease.
    British Journal of Cancer 03/1995; 71(2):326-30. DOI:10.1038/bjc.1995.65 · 4.84 Impact Factor
Show more