OBJECTIVETo compare the efficacy and safety of standard or reduced doses of bortezomib combined with adriamycin and dexamethasone (PAD) in patients with multiple myeloma (MM).

METHODSEighty-two newly diagnosed or refractory/relapsed patients received bortezomib [either 1.2-1.3 mg/m(2) (standard dose) or 1.0-1.1 mg/m(2) (reduced dose) on day 1, 4, 8 and 11], and adriamycin (10 mg/m(2)) plus dexamethasone (40 mg/m(2)) on day 1-4 at 3-week intervals for 1 to 6 courses. The International Myeloma Working Group Criteria were used to evaluate the response. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria (Version 3.0).

RESULTSTwo courses of standard dose of PAD resulted in a similar response rate of partial and very good partial complete remissions (PR) compared with reduced dose (80.0% vs 80.8%, P=0.728). Grade III- Ⅳ neutropenia and thrombocytopenia were higher with standard dose than that with reduced doses of PAD (21.1% vs11.1%, P=0.270; 10.5% vs 6.3%, P=0.619, respectively). Grade III-Ⅳ bortezomib-induced peripheral neuropathy, herpes zoster, fatigue or abdominal distention were significantly higher with standard dose than that with reduced dose of PAD (15.8% vs 1.6%, P=0.037; 26.3% vs 6.3%, P=0.028; 36.8% vs 14.3%, P=0.046; 15.8% vs 1.6%, P=0.037, respectively).

CONCLUSIONReduced dose of PAD appears to result in a similar overall response rate, but a better tolerance and safety compared with standard dose.

Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Boronic Acids ; administration & dosage ; adverse effects ; therapeutic use ; Bortezomib ; Dexamethasone ; administration & dosage ; adverse effects ; Doxorubicin ; administration & dosage ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Pyrazines ; administration & dosage ; adverse effects ; therapeutic use ; Treatment Outcome

OBJECTIVETo evaluate the efficacy and safety of bortezomib retreatment in 76 patients with relapsed/refractory multiple myeloma (MM), who previously responded to bortezomib.

METHODSRetrospective analysis of 76 MM patients, who had achieved at least a partial response (PR) on initial bortezomib therapy in our hospital from May 2006 to August 2011, received bortezomib retreatment when they relapsed or progressed.

RESULTSThe overall response rate (ORR) was 60.5%, among them 6.5% patients achieved CR, 5.8% patients achieved very good partial response (VGPR), 38.2% patients achieved PR. Then we further stratified all patients into 3 groups according to the response of initial bortezomib therapy, including CR group, VGPR group and PR group. After bortezomib retreatment, the ORR of the 3 groups was 84.6%, 73.1% and 43.2%, respectively. According to the response of bortezomib retreatment, the patients were divided into 2 groups: group 1 who at least achieved PR, group 2 who showed no response. The median progression-free survival (PFS) after bortezomib retreatment for group 1 and 2 was 7(1-39) and 5(1-14) months, respectively (P>0.05), while the median overall survival (OS) after bortezomib retreatment was 16(2-64) and 8(1-28) months, respectively (P<0.05). Adverse events (AE) were identified in 88% patients during bortezomib retreatment, including neutropenia, diarrhea and thrombocytopenia, only 9.2%(7 patients) reached Ⅲ-Ⅳ grade of AE. Severe peripheral neuropathy occurred in only one patient.

CONCLUSIONBortezomib retreatment regimen is demonstrated a higher response rate in patients who achieved deeper response in initial treatment, with no more adverse events.

Adult ; Aged ; Boronic Acids ; adverse effects ; therapeutic use ; Bortezomib ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Pyrazines ; adverse effects ; therapeutic use ; Retrospective Studies ; Treatment Outcome

BACKGROUNDWhether the sequential treatment with bortezomib plus dexamethasone (BD) followed by autologous hematopoietic stem cell transplantation (ASCT) could extend the overall survival period in multiple myeloma patients is still not clear. Few large case studies about this therapeutics in multiple myeloma were reported in China. Our purpose was to assess the efficacy and adverse effects of sequential treatment with BD chemotherapy and ASCT in patients with multiple myeloma.

METHODSFifty-three patients with newly diagnosed or relapsed/refractory multiple myeloma received BD as induction therapy before ASCT. Stem-cell mobilization was undertaken with cyclophosphamide 3 - 5 g/m(2) plus granulocyte colony-stimulating factor 300 µg/d. Target yield was 2.0×10(6) CD34(+) cells/kg. Conditioning for ASCT consisted of melphalan 200 mg/m(2). Thalidomide and/or a-interferon was used as post-transplantation maintenance treatment.

RESULTSThe BD chemotherapy before transplantation was effective in 86.7% of the 53 patients, including 22.6% with complete remission (CR), 39.6% with near complete remission (nCR), and 24.5% with partial remission (PR). The best effect was achieved after two treatment courses. Most bortezomib-related adverse effects were classes 1 - 2. All patients were successfully mobilized after BD for autologous peripheral blood stem cell transplantation. The ASCT was effective in 96.3% of patients, including 49.1% with CR, 32.1% with nCR, and 15.1% with PR. The CR rate was significantly increased (49.1% vs. 22.6%, P < 0.05) by sequential ASCT. Within 27 (range, 6 - 53) months of follow-up, the efficacy of ASCT was maintained in 29 patients and further enhanced by post-transplantation maintenance treatment in four patients. Eleven patients died after transplantation. Among the patients undergoing BD/ASCT treatment, overall survival (OS) was significantly better in newly diagnosed patients in comparison to relapsed/refractory patients (P = 0.046).

CONCLUSIONSBD chemotherapy can be used as an induction therapy prior to ASCT in patients with multiple myeloma. Its rate of effectiveness is high and it alleviates symptoms quickly without affecting peripheral blood stem cell collection. The majority of adverse effects are mild (tolerable). Sequential BD with ASCT is the preferred option for transplant patients. First-line ASCT could prolong survival of newly diagnosed patients rather than delayed ASCT.

Adult ; Aged ; Boronic Acids ; administration & dosage ; adverse effects ; therapeutic use ; Bortezomib ; Dexamethasone ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; therapy ; Pyrazines ; administration & dosage ; adverse effects ; therapeutic use ; Treatment Outcome

This study was purposed to analyze the clinical characteristics of multiple myeloma (MM) patients with and without renal impairment (RI) and to investigate the effect of bortezomib (Bor) on MM with RI. Clinical data of 39 MM patients (15 cases with RI, 24 cases without RI) received treatment of Bor in department of hematology in our hospital from Jan 2007 to Aug 2011 were collect and analyzed in term of clinical characteristics, curative efficacy, outcome of renal impairment and toxic reaction associated to chemotherapy. The results showed that (1) the obvious difference of the disease type, the creatinine, uric acid, serum calcium and β2-microglobulin levels existed in patients with and without RI, while there were no significant difference in hemoglobin and globin levels; (2) there were no significant difference in overall reaction rate and overall survival rate between MM patients with and without RI, however the median survival time of patients without RI was longer than that of patients with RI; (3) the RI could be reversed after the treatment with Bor, and the effect was most obvious after the first cycle. 20% MM patients with RI had recovered from RI after the first cycle; and the recovery rate from RI got up to 38.4% after the second cycle. The decline of creatinine levels had no difference between MM patients with or without RI after the second cycle. (4) The adverse events included gastrointestinal symptoms, peripheral neuropathy, thrombocytopenia and infection. There was also no difference between the 2 groups. It is concluded that Bor-based regimens for the MM patients with RI are effective and safe, and the renal function would be reversed after 2 cycle of Bor-based regimen.
Adult ; Aged ; Aged, 80 and over ; Boronic Acids ; adverse effects ; therapeutic use ; Bortezomib ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; physiopathology ; Pyrazines ; adverse effects ; therapeutic use ; Renal Insufficiency

OBJECTIVETo review this efficacy and safety of bortezomib, a proteasome inhibitor, in the setting of the sensitized transplant candidate.

DATA SOURCESThe data used in this review were from articles published (PubMed) between 2000 to 2010. Additionally abstracts from medical meetings related to transplant were also used.

STUDY SELECTIONArticles were selected if they were trial results or case studies for the use of bortezomib in the sensitized patient population.

RESULTSThe early data using bortezomib as a part of desensitization regimens has shown success. Although one cycle (4 doses) of bortezomib seems to have affect on many patients, it also seems likely that to provide complete desensitization multiple cycles will be required. Regarding safety, bortezomib has been shown to have minimal side effects. The most common side effects reported are those of thrombocytopenia and anemia. These side effects are dose related and self limiting upon discontinuation of the treatment.

CONCLUSIONSBortezomib with plasmapheresis is a promising new alternative to desensitization protocols that use either high dose intravenous immune globulin (IVIG) or low dose IVIG and plasmapheresis. The efficacy on antibody reduction looks to be batter that that of the IVIG based regimens without significant addition toxicity. The results of ongoing prospective trials are positive and their complete results are greatly anticipated.

Boronic Acids ; therapeutic use ; Bortezomib ; Graft Rejection ; immunology ; prevention & control ; Humans ; Protease Inhibitors ; therapeutic use ; Proteasome Endopeptidase Complex ; metabolism ; Pyrazines ; therapeutic use ; Transplants ; adverse effects

OBJECTIVETo study the mechanism of bortezomib inducing peripheral neuropathy and the reversing affection of reduced glutathione.

METHODSFemale Wistar rats were randomly divided into three groups. Group 1, treatment with bortezomib; Group 2, treatment with bortezomib and reduced glutathione; Group 3, saline control group. Drugs were administrated on the 1st, 4th, 7th and 11th day for the three groups. The amorphous of sciatic nerve and dorsal root ganglion (DRG) were observed by electron microscope on 14th and 42nd day. On 14th day, laser confocal microscopy was used to detect reactive oxygen species (ROS) of DRG neuron obtained from the rats by treated with DCFH-DA after primary culture.

RESULTSOn 14th day, morphology of sciatic nerve and DRG changed in both group 1 and 2. On 42nd day, the amorphous became normally in group 1. On 14th day, ROS releasing from DRG neuron was increased obviously in group 1 (P < 0.01), while decreased in both group 2 and 3, and the difference between the latter two groups had no statistical significance (P = 0.210).

CONCLUSIONReleasing ROS to injure mitochondrion and endoplasmic reticulum maybe involved in bortezomib induced peripheral neuropathy. Although reduced glutathione can inhibit ROS release, it has no obviously reversal effect for peripheral neuropathy.

Animals ; Boronic Acids ; adverse effects ; Bortezomib ; Female ; Glutathione ; therapeutic use ; Peripheral Nervous System Diseases ; chemically induced ; metabolism ; prevention & control ; Pyrazines ; adverse effects ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; metabolism

Boronic Acids ; adverse effects ; Bortezomib ; Fatty Acids, Omega-3 ; administration & dosage ; therapeutic use ; Fish Oils ; administration & dosage ; therapeutic use ; Humans ; Male ; Middle Aged ; Peripheral Nervous System Diseases ; chemically induced ; drug therapy ; Pyrazines ; adverse effects

Bortezomib is an inhibitor of 26S proteasome, which is an effective treatment for multiple myeloma. The common adverse effects of bortezomib are asthenic conditions, gastrointestinal disturbances, and peripheral neuropathy. Here we describe a patient with dyspnea and general weakness because of complete atrioventricular block while receiving bortezomib. We immediately stopped bortezomib, and after inserting a permanent VDD pacemaker, the patients' symptoms disappeared.
Atrioventricular Block/*chemically induced ; Boronic Acids/*adverse effects/*therapeutic use ; Female ; Humans ; Middle Aged ; Multiple Myeloma/*drug therapy ; Pyrazines/*adverse effects/*therapeutic use

Bortezomib is an inhibitor of 26S proteasome, which is an effective treatment for multiple myeloma. The common adverse effects of bortezomib are asthenic conditions, gastrointestinal disturbances, and peripheral neuropathy. Here we describe a patient with dyspnea and general weakness because of complete atrioventricular block while receiving bortezomib. We immediately stopped bortezomib, and after inserting a permanent VDD pacemaker, the patients' symptoms disappeared.
Atrioventricular Block/*chemically induced ; Boronic Acids/*adverse effects/*therapeutic use ; Female ; Humans ; Middle Aged ; Multiple Myeloma/*drug therapy ; Pyrazines/*adverse effects/*therapeutic use

The study was aimed to evaluate the adverse effects of PAD (bortezomib + adriamycin + dexamethasone) and VAD (vincristine + adriamycin + dexamethasone) as chemotherapy regimens in multiple myeloma patients. 27 and 30 patients with multiple myeloma (MM) were enrolled in PAD and VAD groups respectively. MM patients accepted 3 - 5 cycles of VAD or PAD regimens. The type, degree and occurrence time of adverse reactions during the treatment were observed. The results showed that the rash was found in two patients only in PAD group, leucocytopenia, thrombocytopenia, peripheral neuropathy, infection, fatigue, nausea, constipation, and adverse effects of cortex hormone (hypertension, glycemia, hypokalemia, hyponatremia and acne) were found in the both two groups. The thrombosis was not observed in both two groups during treatment. Although statistical analysis indicated that only the incidence of thrombocytopenia was higher in PAD group than in VAD group with statistical difference but the incidence of leucocytopenia, peripheral neuropathy and infection in PAD group were higher than those in VAD group. Rash, constipation, peripheral neuropathy could be found in the first course of chemotherapy, while the others mostly emerged after 3 courses of treatment. The main reasons for the patients who's treatment was stopped include infection and intolerable peripheral neuropathy. Although peripheral neuropathy could be found in the two groups, but the chemotherapy was stopped only in 2 patients of PAD group after 3 cycles of treatment. It is concluded that compared with conventional VAD chemotherapy, PAD may improve therapeutic effect, but it may bring more severe toxicities to the patients with multiple myeloma.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Boronic Acids ; administration & dosage ; Bortezomib ; Dexamethasone ; adverse effects ; therapeutic use ; Doxorubicin ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Pyrazines ; administration & dosage ; Vincristine ; adverse effects ; therapeutic use