Published by the IC
nternational M I
yeloma FT
oundation
ING
VOLUME V, ISSUE III S
Q3/2008
VELCADE® (bortezomib) Issue
Welcome to the International Myeloma Foundation's (IMF) special edition of CITINGS,
our premiere publication featuring the most up-to-date information on myeloma treatment.
This issue focuses on VELCADE (bortezomib), the first of a new class of drugs called proteasome
inhibitors. In this issue, we provide a list of references to the latest publications from the
third quarter of 2008 on bortezomib from both national and international medical journals
and publications.
We hope that CITINGS provides a detailed and informative update of the VELCADE literature.
Please feel free to contact the IMF at (800) 452-CURE or www.myeloma.org
Susie Novis, President, IMF
VELCADE® Publications 3rd Quarter, 2008
NBortezomib in multiple myeloma.
Terpos E, Roussou M, Dimopoulos MA.
Expert Opin Drug Metab Toxicol. 2008 May;4(5):639-54.
:
http://www.ncbi.nlm.nih.gov/pubmed/18484921?ordinalpos=137&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_
RVDocSum
This article summarizes the chemistry, pharmacokinetics and metabolism of bortezomib, and reviews its clinical efficacy and toxicity,
including use in elderly patients, use in patients with renal impairment and/or a poor prognosis, and effects on bone metabolism.
NFatty acid synthase is a novel therapeutic target in multiple myeloma.
Okawa Y, Hideshima T, Ikeda H, Raje N, Vallet S, Kiziltepe T, Yasui H, Enatsu S, Pozzi S, Breitkreutz I, Cirstea D, Santo L,
Richardson P, Anderson KC.
Br J Haematol. 2008 May;141(5):659-71. [Epub 2008 Apr 10.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18410446?ordinalpos=125&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_
RVDocSum
This study investigates the biological significance of the inhibition of fatty acid synthase in multiple myeloma using the small molecule
inhibitor Cerulenin and finds in part that Cerulenin shows synergistic cytotoxic effects with various agents, including bortezomib.
www.myeloma.org
(800) 452 - CURE (2873)
Funded by an educational grant from Millennium: The Takeda Oncology Company
Np38 mitogen-activated protein kinase inhibitor LY2228820 enhances bortezomib-induced cytotoxicity
and inhibits osteoclastogenesis in multiple myeloma; therapeutic implications.
Ishitsuka K, Hideshima T, Neri P, Vallet S, Shiraishi N, Okawa Y, Shen Z, Raje N, Kiziltepe T, Ocio EM, Chauhan D, Tassone P,
Munshi N, Campbell RM, Dios AD, Shih C, Starling JJ, Tamura K, Anderson KC.
Br J Haematol. 2008 May;141(5):598-606. [Epub 2008 Apr 7.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18397345?ordinalpos=126&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_
RVDocSum
The authors' findings suggest that inhibitor LY2228820 represents a promising novel targeted approach to improve myeloma patient
outcome both by enhancing the effect of bortezomib and by reducing osteoskeletal events.
NNew therapeutic strategies for multiple myeloma. Efficacy and cost-effectiveness analyses. [Article in Spanish]
García Quetglas E, Azanza Perea JR, Lecumberri Villamediana R.
Med Clin (Barc). 2008 May 3;130(16):626-35.
:
http://www.ncbi.nlm.nih.gov/pubmed/18482531?ordinalpos=119&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_
RVDocSum
The article reviews the most important therapeutic innovations in the treatment of myeloma in terms of efficacy and cost-effectiveness,
including a discussion of bortezomib.
NThe addition of liposomal doxorubicin to bortezomib, thalidomide and dexamethasone significantly improves
clinical outcome of advanced multiple myeloma.
Ciolli S, Leoni F, Casini C, Breschi C, Santini V, Bosi A.
Br J Haematol. 2008 Jun;141(6):814-9. [Epub 2008 Apr 10.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18410447?ordinalpos=84&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
In this study, liposomal doxorubicin is added to a bortezomib/thalidomide/ dexamethasone ( VTD) treatment in relapsed/refractory
myeloma patients. The authors find increased overall response rate and progression-free survival with this combination, compared
to VTD alone and that toxicity is manageable although more pronounced.
NBortezomib, doxorubicin and dexamethasone in advanced multiple myeloma.
Palumbo A, Gay F, Bringhen S, Falcone A, Pescosta N, Callea V, Caravita T, Morabito F, Magarotto V, Ruggeri M, Avonto I,
Musto P, Cascavilla N, Bruno B, Boccadoro M.
Ann Oncol. 2008 Jun;19(6):1160-5. [Epub 2008 Mar 6.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18326520?ordinalpos=82&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The authors assess for the first time the combination of bortezomib, doxorubicin and low-dose dexamethasone (PAd) in the treatment
of relapsed/refractory myeloma and find that Pad is an active salvage therapy with manageable toxicity in patients with relapsed/
refractory myeloma.
NClinical implications of bortezomib in frontline treatment of newly-diagnosed multiple myeloma.
[Article in Japanese]
Ohashi K.
Gan To Kagaku Ryoho. 2008 Jun;35(6):1029-32.
:
http://www.ncbi.nlm.nih.gov/pubmed/18633240?ordinalpos=96&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
This review focuses on the clinical data based on the previous studies of bortezomib in the treatment of newly diagnosed myeloma.
NFeatures and risk factors of peripheral neuropathy during treatment with bortezomib for advanced
multiple myeloma.
El-Cheikh J, Stoppa AM, Bouabdallah R, de Lavallade H, Coso D, de Collela JM, Auran-Schleinitz T, Gastaut JA, Blaise D, Mohty M.
Clin Lymphoma Myeloma. 2008 Jun;8(3):146-52.
:
http://www.ncbi.nlm.nih.gov/pubmed/18650177?ordinalpos=91&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
This retrospective, single-center study aims to determine the characteristics of bortezomib-associated peripheral neuropathy (PN).
It concludes that, though relatively frequent, bortezomib-associated PN is reversible in a majority of patients and that bortezomib-
associated PN seems to be dependent on previous therapy with thalidomide, suggesting that bortezomib followed by thalidomide could
be an optimal sequence of administration of these drugs in the salvage setting.
www.myeloma.org
(800) 452 - CURE (2873)
NGastrointestinal side effects associated with novel therapies in patients with multiple myeloma:
consensus statement of the IMF Nurse Leadership Board.
Smith LC, Bertolotti P, Curran K, Jenkins B; IMF Nurse Leadership Board.
Clin J Oncol Nurs. 2008 Jun;12(3 Suppl):37-52.
:
http://www.ncbi.nlm.nih.gov/pubmed/18490256?ordinalpos=88&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The International Myeloma Foundation's Nurse Leadership Board develops a consensus statement for the management of
gastrointestinal side effects associated with novel therapies, including bortezomib, to be used by healthcare providers in any
medical setting.
NHemostatic effects of bortezomib treatment in patients with relapsed or refractory multiple myeloma.
Zangari M, Guerrero J, Cavallo F, Prasad HK, Esseltine D, Fink L.
Haematologica. 2008 Jun;93(6):953-4.
:
http://www.ncbi.nlm.nih.gov/pubmed/18515882?ordinalpos=97&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
No abstract available.
NMaintenance treatment in multiple myeloma.
Harousseau JL.
Ann Oncol. 2008 Jun;19 Suppl 4:iv54-5.
:
http://www.ncbi.nlm.nih.gov/pubmed/18519405?ordinalpos=81&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
No abstract available.
NMyelosuppression associated with novel therapies in patients with multiple myeloma: consensus statement of
the IMF Nurse Leadership Board.
Miceli T, Colson K, Gavino M, Lilleby K; IMF Nurse Leadership Board.
Clin J Oncol Nurs. 2008 Jun;12(3 Suppl):13-20.
:
http://www.ncbi.nlm.nih.gov/pubmed/18490253?ordinalpos=90&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The International Myeloma Foundation's Nurse Leadership Board developed a consensus statement that includes toxicity grading,
strategies for monitoring and managing myelosuppression associated with novel therapies, including bortezomib, and offers educational
recommendations for patients and their caregivers.
NAn observational, retrospective analysis of retreatment with bortezomib for multiple myeloma.
Conner TM, Doan QD, Walters IB, LeBlanc AL, Beveridge RA.
Clin Lymphoma Myeloma. 2008 Jun;8(3):140-5.
:
http://www.ncbi.nlm.nih.gov/pubmed/18650176?ordinalpos=92&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
This retrospective chart review of patients with myeloma aims to describe patterns of re-treatment with bortezomib-based therapy and
responses to re-treatment in a community-based setting. It concludes that re-treatment with bortezomib-based therapy is feasible, with
predictable toxicities; this observational analysis supports bortezomib alone or in combination as a re-treatment option after initial
bortezomib treatment in patients with relapsed myeloma.
NPeripheral neuropathy associated with novel therapies in patients with multiple myeloma: consensus
statement of the IMF Nurse Leadership Board.
Tariman JD, Love G, McCullagh E, Sandifer S; IMF Nurse Leadership Board.
Clin J Oncol Nurs. 2008 Jun;12(3 Suppl):29-36.
:
http://www.ncbi.nlm.nih.gov/pubmed/18490255?ordinalpos=89&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The International Myeloma Foundation Nurse Leadership Board provides specific management strategies for peripheral neuropathy
caused by novel therapies, including bortezomib, based on the grade of severity and on signs and symptoms; strategies include dose
and schedule modifications, pharmacologic interventions, nonpharmacologic approaches, and patient education.
www.myeloma.org
(800) 452 - CURE (2873)
NThe potential of proteasome inhibitors in cancer therapy.
Sterz J, von Metzler I, Hahne JC, Lamottke B, Rademacher J, Heider U, Terpos E, Sezer O.
Expert Opin Investig Drugs. 2008 Jun;17(6):879-95.
:
http://www.ncbi.nlm.nih.gov/pubmed/18491989?ordinalpos=94&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
This review focuses both on preclinical results and on data from clinical trials with proteasome inhibitors in cancer and concludes that
bortezomib as first-in-class proteasome inhibitor that has proven to be highly effective in some hematological malignancies, overcomes
conventional chemoresistance, directly induces cell cycle arrest and apoptosis, and also targets the tumor microenvironment.
NProteasome Inhibitor Induces Apoptosis and Influences the Expression of Notch 1 and NF-kappaB in Multiple
Myeloma RPMI8226 Cells. [Article in Chinese]
Wang H, Liu X, Xu B.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008 Jun;16(3):531-7.
:
http://www.ncbi.nlm.nih.gov/pubmed/18549623?ordinalpos=109&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_
RVDocSum
The authors investigate the effects of bortezomib inducing cell apoptosis and influencing the expression of Notch1 and NF-kappaB in
multiple myeloma RPMI 8226 cells. They conclude that Notch1 and NF-kappaB signaling pathways participate in bortezomib-inducing
RPMI8226 cell apoptosis and that there may be some correlation between the Notch 1 and NF-kappaB signaling pathways, indicating
that Notch 1 signal may be a latent target in treating myeloma.
NUpdated follow-up of patients treated with bortezomib for relapsed multiple myeloma.
Santini D, Vincenzi B, Tonini G.
Nat Clin Pract Oncol. 2008 Jun;5(6):304-5. [Epub 2008 Apr 29.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18446143?ordinalpos=106&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_
RVDocSum
Comment on: Blood. 2007 Nov 15;110(10):3557-60.
NFrontline treatment of multiple myeloma in elderly patients.
Moreau P, Hulin C, Facon T.
Blood Rev. 2008 Jun 10. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18550234?ordinalpos=72&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
This article discusses highly active new treatment options now available to treat elderly patients with myeloma,
including melphalan-prednisone-bortezomib.
NCompletion of premaintenance phases in total therapies 2 and 3 improves clinical outcomes in multiple
myeloma: an important variable to be considered in clinical trial designs.
Barlogie B, Haessler J, Pineda-Roman M, Anaissie E, van Rhee F, Kiwan E, Steward D, Gurley J, Jenkins B, Crowley J.
Cancer. 2008 Jun 15;112(12):2720-5.
:
http://www.ncbi.nlm.nih.gov/pubmed/18433012?ordinalpos=69&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
This study of treatment protocols results in data supporting the beneficial role of bortezomib in the treatment of myeloma.
NThe novel polyamine analogue CGC-11093 enhances the antimyeloma activity of bortezomib.
Carew JS, Nawrocki ST, Reddy VK, Bush D, Rehg JE, Goodwin A, Houghton JA, Casero RA Jr, Marton LJ, Cleveland JL.
Cancer Res. 2008 Jun 15;68(12):4783-90.
:
http://www.ncbi.nlm.nih.gov/pubmed/18559525?ordinalpos=70&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The authors report that CGC-11093 selectively augments the in vitro and in vivo antimyeloma activity of bortezomib, findings
that support the study of the use of the combination of bortezomib and CGC-11093 in myeloma patients who fail to respond to
frontline therapy.
www.myeloma.org
(800) 452 - CURE (2873)
NMolecular basis of bortezomib/Velcade(R) resistance: proteasome subunit {beta}5 (PSMB5) gene mutation
and overexpression of PSMB5 protein.
Oerlemans R, Franke NE, Assaraf YG, Cloos J, van Zantwijk I, Berkers CR, Scheffer GL, Debipersad K, Vojtekova K, Lemos C,
van der Heijden JW, Ylstra B, Peters GJ, Kaspers GL, Dijkmans BA, Scheper RJ, Jansen G.
Blood. 2008 Jun 18. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18565852?ordinalpos=65&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The authors' findings establish a novel mechanism of bortezomib-resistance associated with the selective overexpression of a mutant
PSMB5 protein.
NBortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature.
Argyriou AA, Iconomou G, Kalofonos HP.
Blood. 2008 Jun 23. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18574024?ordinalpos=62&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The authors review the pathogenesis, incidence, risk factors, diagnosis, characteristics and management of bortezomib-induced
peripheral neuropathy and highlight areas of future research to pursue.
NBortezomib in the front-line treatment of multiple myeloma.
Richardson PG, Mitsiades C, Schlossman R, Ghobrial I, Hideshima T, Munshi N, Anderson KC.
Expert Rev Anticancer Ther. 2008 Jul;8(7):1053-72.
:
http://www.ncbi.nlm.nih.gov/pubmed/18588451?ordinalpos=49&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The authors discuss the rapid evolution of front-line therapy for multiple myeloma with the development of new, highly active regimens
based on novel agents such as bortezomib.
NChemotherapy-induced peripheral neuropathy: Prevention and treatment strategies.
Wolf S, Barton D, Kottschade L, Grothey A, Loprinzi C.
Eur J Cancer. 2008 Jul;44(11):1507-15. [Epub 2008 Jun 18.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18571399?ordinalpos=48&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
This article provides a review of studies conducted to look at ways of preventing or alleviating established chemotherapy-induced
peripheral neuropathy (CIPN), including CIPN as a side effect of bortezomib treatment.
NNF-kappaB in the pathogenesis and treatment of multiple myeloma.
Li ZW, Chen H, Campbell RA, Bonavida B, Berenson JR.
Curr Opin Hematol. 2008 Jul;15(4):391-9.
:
http://www.ncbi.nlm.nih.gov/pubmed/18536579?ordinalpos=47&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
This review summarizes recent advances in the mechanisms through which the activation of the transcription factor NF-kappaB
contributes to the pathogenesis of myeloma, including the finding that several drugs that are effective against myeloma, including
bortezomib, also block activation of NF-kappaB.
NOsteoprogenitor differentiation is not affected by immunomodulatory thalidomide analogs but is
promoted by low bortezomib concentration, while both agents suppress osteoclast differentiation.
Munemasa S, Sakai A, Kuroda Y, Okikawa Y, Katayama Y, Asaoku H, Kubo T, Shimose S, Kimura A.
Int J Oncol. 2008 Jul;33(1):129-36.
:
http://www.ncbi.nlm.nih.gov/pubmed/18575758?ordinalpos=50&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The authors investigate the effects of bortezomib and immunomodulatory thalidomide analogs (including lenalidomide) on
osteoblast and osteoclast differentiation in vitro. They conclude that by combining bortezomib with immunomodulatory
compounds, it is possible to improve treatment strategy for myeloma patients without damaging BM stromal cells.
www.myeloma.org
(800) 452 - CURE (2873)
NProspective evaluation of coagulopathy in multiple myeloma patients before, during and after various
chemotherapeutic regimens.
van Marion AM, Auwerda JJ, Lisman T, Sonneveld P, de Maat MP, Lokhorst HM, Leebeek FW.
Leuk Res. 2008 Jul;32(7):1078-84. [Epub 2008 Feb 1.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18241919?ordinalpos=52&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The authors perform a prospective study in myeloma patients in whom coagulation factor levels are evaluated longitudinally before,
during induction and after intensification. Patients are randomized to induction treatment consisting of adriamycin and dexamethasone,
in combination with either vincristine, thalidomide, or bortezomib followed by high-dose melphalan and autologous stem cell
transplant. The authors find that during induction treatment several changes in coagulation factor levels are observed, which may result
in a prothrombotic state. They conclude that larger studies are required to establish whether the changes in these coagulation factors
during induction treatment contribute to the increased risk of venous thromboembolism in myeloma patients.
NVTD combination therapy with bortezomib-thalidomide-dexamethasone is highly effective in advanced and
refractory multiple myeloma.
Pineda-Roman M, Zangari M, van Rhee F, Anaissie E, Szymonifka J, Hoering A, Petty N, Crowley J, Shaughnessy J,
Epstein J, Barlogie B.
Leukemia. 2008 Jul;22(7):1419-27. [Epub 2008 Apr 24.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18432260?ordinalpos=55&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
In this study, bortezomib was combined with thalidomide and dexamethasone in a phase I/II trial to determine dose-limiting toxicities
and clinical activity of this regimen in 85 patients with advanced and refractory myeloma.
NBortezomib: a novel chemotherapeutic agent for hematologic malignancies.
Utecht KN, Kolesar J.
Am J Health Syst Pharm. 2008 Jul 1;65(13):1221-31.
:
http://www.ncbi.nlm.nih.gov/pubmed/18574011?ordinalpos=39&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
This article reviews the pharmacolog y, pharmacokinetics, clinical efficacy, safety, dosage and administration, place in therapy, and cost
of bortezomib in the treatment of multiple myeloma and mantle cell lymphoma.
NMultiple Myeloma, an update on diagnosis and treatment.
Caers J, Vande Broek I, De Raeve H, Michaux L, Trullemans F, Schots R, Van Camp B, Vanderkerken K.
Eur J Haematol. 2008 Jul 11. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18637123?ordinalpos=34&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
This article updates the new approaches in the diagnosis and treatment of myeloma, including new agents such as bortezomib.
NA novel therapeutic combination using PD 0332991 and bortezomib: study in the 5T33MM myeloma model.
Menu E, Garcia J, Huang X, Di Liberto M, Toogood PL, Chen I, Vanderkerken K, Chen-Kiang S.
Cancer Res. 2008 Jul 15;68(14):5519-23.
:
http://www.ncbi.nlm.nih.gov/pubmed/18632601?ordinalpos=33&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The authors find that inhibition of Cdk4/6 by PD 0332991 effectively controls myeloma tumor expansion and sensitizes tumor cells
to bortezomib killing in the presence of an intact immune system, thereby representing a novel and promising cell cycle-based
combination therapy.
NDietary flavonoids inhibit the anti-cancer effects of the proteasome inhibitor Bortezomib.
Liu FT, Agrawal SG, Movasaghi Z, Wyatt PB, Rehman IU, Gribben JG, Newland AC, Jia L.
Blood. 2008 Jul 16. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18633129?ordinalpos=32&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The authors discuss data indicating that that dietary flavonoids limit the efficacy of bortezomib.
www.myeloma.org
(800) 452 - CURE (2873)
NPhase I-II Trial of Bortezomib Plus Oral Cyclophosphamide and Prednisone in Relapsed and Refractory
Multiple Myeloma.
Reece DE, Piza Rodriguez G, Chen C, Trudel S, Kukreti V, Mikhael J, Pantoja M, Xu W, Stewart AK.
J Clin Oncol. 2008 Jul 21. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18645194?ordinalpos=27&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The authors seek to improve the efficacy of the combination of oral weekly cyclophosphamide and alternate day prednisone
regimen for relapsed/refractory multiple myeloma by adding bortezomib. They find that weekly bortezomib 1.5 mg/m(2) plus oral
cyclophosphamide and prednisone produces an unprecedented response rate and encouraging 1-year survival in relapsed/refractory
patients with myeloma.
NAdvances in and applications of proteasome inhibitors.
Moore BS, Eustáquio AS, McGlinchey RP.
Curr Opin Chem Biol. 2008 Jul 24. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18656549?ordinalpos=26&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
This review highlights recent advances in the development and application of proteasome inhibitors, including bortezomib.
NTargeting TRAIL death receptors.
Oldenhuis C, Stegehuis J, Walenkamp A, de Jong S, de Vries E.
Curr Opin Pharmacol. 2008 Jul 28. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18625341?ordinalpos=25&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The authors in part discuss the mechanisms to sensitize tumors cells to rhTRAIL by combination with bortezomib.
NThe relationship between quality of response and clinical benefit for patients treated on the bortezomib arm
of the international, randomized, phase 3 APEX trial in relapsed multiple myeloma.
Niesvizky R, Richardson PG, Rajkumar SV, Coleman M, Rosiñol L, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T,
Harousseau JL, Boral AL, Esseltine DL, Anderson KC, Bladé J.
Br J Haematol. 2008 Jul 31. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18673366?ordinalpos=24&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
This study assesses bortezomib versus dexamethasone in relapsed myeloma and the relationship between quality of response to
bortezomib and clinical benefit. The authors conclude that bortezomib had substantial activity in relapsed myeloma patients and that
complete remission may be a surrogate marker for significant clinical benefit with bortezomib.
NBortezomib and the increased incidence of herpes zoster in patients with multiple myeloma.
Kim SJ, Kim K, Kim BS, Lee HJ, Kim H, Lee NR, Nam SH, Kwon JH, Kim HJ, Sohn SK, Won JH, Lee JH, Suh C, Yoon SS, Kim HJ,
Kim I, Do YR, Lee WS, Joo YD, Shin HJ.
Clin Lymphoma Myeloma. 2008 Aug;8(4):237-40.
:
http://www.ncbi.nlm.nih.gov/pubmed/18765311?ordinalpos=37&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The authors perform a retrospective analysis of the incidence of herpes zoster among 282 patients treated with a bortezomib-containing
regimen and conclude that bortezomib can increase the incidence of herpes zoster regardless of disease duration, previous treatments,
and concomitantly administered drugs; the occurrence of herpes zoster should therefore be monitored during bortezomib treatment.
NBortezomib-resistant nuclear factor-kappaB activity in multiple myeloma cells.
Markovina S, Callander NS, O'Connor SL, Kim J, Werndli JE, Raschko M, Leith CP, Kahl BS, Kim K, Miyamoto S.
Mol Cancer Res. 2008 Aug;6(8):1356-64.
:
http://www.ncbi.nlm.nih.gov/pubmed/18708367?ordinalpos=47&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The authors report an unexpected finding that constitutive NF-kappaB activity in 10 of 14 primary myeloma samples analyzed is
refractory to inhibition by bortezomib.
www.myeloma.org
(800) 452 - CURE (2873)
NCaspase-2 functions upstream of mitochondria in endoplasmic reticulum stress-induced apoptosis by
bortezomib in human myeloma cells.
Gu H, Chen X, Gao G, Dong H.
Mol Cancer Ther. 2008 Aug;7(8):2298-307.
:
http://www.ncbi.nlm.nih.gov/pubmed/18723477?ordinalpos=48&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The authors' data strongly suggest that caspase-2 can serve as a proximal caspase that functions upstream of mitochondrial signaling
during endoplasmic reticulum stress-induced apoptosis by bortezomib in multiple myeloma cells.
NClinical study of bortezomib in combination with dexamethasone for the treatment of multiple myeloma.
[Article in Chinese]
Wang LX, Lu H, Shen WY, Qian SX, Qiu HX, Wu HX, Zhang JF, Wu YJ, Li JY.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008 Aug;16(4):943-5.
:
http://www.ncbi.nlm.nih.gov/pubmed/18718096?ordinalpos=48&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The authors evaluate the efficiency and safety of bortezomib for the treatment of myeloma by administering it as first-line treatment
in combination with dexamethasone in 7 newly diagnosed patients. They conclude that bortezomib demonstrates efficiency in the
treatment of newly diagnosed and refractory/relapsed multiple myeloma, and the side effects from treatment are acceptable and
manageable.
NPathogenesis and treatment of renal failure in multiple myeloma.
Dimopoulos MA, Kastritis E, Rosinol L, Bladé J, Ludwig H.
Leukemia. 2008 Jun 5. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18528426?ordinalpos=76&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The authors discuss renal failure as a frequent complication in patients with multiple myeloma, and address data that suggest that
bortezomib may be beneficial in this population.
NThe role of high-dose chemotherapy followed by peripheral blood stem cell transplantation
for the treatment of multiple myeloma.
Siddiqui M, Gertz M.
Leuk Lymphoma. 2008 Aug;49(8):1436-51.
:
http://www.ncbi.nlm.nih.gov/pubmed/18608872?ordinalpos=42&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
This review summarizes the role of stem cell transplantation in myeloma and how the advent of novel therapies, such bortezomib, have
started to redefine the role of peripheral stem cell transplantation.
NSafety and efficacy of bortezomib and melphalan combination in patients with relapsed or refractory multiple
myeloma: updated results of a phase 1/2 study after longer follow-up.
Berenson JR, Yang HH, Vescio RA, Nassir Y, Mapes R, Lee SP, Wilson J, Yellin O, Morrison B, Hilger J, Swift R.
Ann Hematol. 2008 Aug;87(8):623-31. [Epub 2008 May 8.]
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http://www.ncbi.nlm.nih.gov/pubmed/18463870?ordinalpos=36&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The authors present updated data from their phase 1/2 study assessing the safety and efficacy of bortezomib plus melphalan in relapsed/
refractory myeloma. They conclude that bortezomib plus melphalan is a steroid- and immunomodulatory drug-free regimen that may
provide a treatment alternative for elderly patients and patients with significant comorbidity.
NTreatment of relapsed and refractory myeloma.
Reece DE, Leitch HA, Atkins H, Voralia M, Canning LA, Leblanc R, Belch AR, White D, Kovacs MJ.
Leuk Lymphoma. 2008 Aug;49(8):1470-85.
:
http://www.ncbi.nlm.nih.gov/pubmed/18608859?ordinalpos=43&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
This article reviews the literature for the treatment of relapsed/refractory myeloma and considers the influence of prior therapy, optimal
sequencing of regimens, sequential versus combination use of agents, and the role of cytogenetic and other prognostic factors, both for
established regimens and newer regimens incorporating thalidomide, bortezomib and lenalidomide.
www.myeloma.org
(800) 452 - CURE (2873)
NWeekly treatment with bortezomib for patients with recurrent or refractory multiple myeloma: a phase 2 trial
of the Minnie Pearl Cancer Research Network.
Hainsworth JD, Spigel DR, Barton J, Farley C, Schreeder M, Hon J, Greco FA.
Cancer. 2008 Aug 15;113(4):765-71.
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http://www.ncbi.nlm.nih.gov/pubmed/18543319?ordinalpos=28&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
This study evaluates the efficacy and toxicity of weekly bortezomib in the treatment of patients with recurrent/refractory multiple
myeloma and finds it to be a reasonable option for patients who have logistic difficulties receiving a twice-weekly schedule, and is an
attractive schedule for incorporation into combination regimens.
NAnalysis of Herpes Zoster Events Among Bortezomib-Treated Patients in the Phase III APEX Study.
Chanan-Khan A, Sonneveld P, Schuster MW, Stadtmauer EA, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H,
Reece D, Neuwirth R, Anderson KC, Richardson PG.
J Clin Oncol. 2008 Aug 18. [Epub ahead of print.]
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http://www.ncbi.nlm.nih.gov/pubmed/18711175?ordinalpos=24&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The study aims to determine if bortezomib treatment is associated with increased incidence of varicella-zoster virus ( VZV) reactivation
in patients with relapsed multiple myeloma and concludes that though further studies are needed, for patients treated with bortezomib
or bortezomib-containing regimens, the risk of VZV reactivation should be monitored and routine use of antiviral prophylaxis
considered.
NCharacterisation of haematological profiles and low risk of thromboembolic events with bortezomib
in patients with relapsed multiple myeloma.
Lonial S, Richardson PG, San Miguel J, Sonneveld P, Schuster MW, Bladé J, Cavenagh J, Rajkumar SV, Jakubowiak AJ, Esseltine DL,
Anderson KC, Harousseau JL.
Br J Haematol. 2008 Aug 18. [Epub ahead of print.]
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http://www.ncbi.nlm.nih.gov/pubmed/18713253?ordinalpos=23&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The authors characterize thrombocytopenia and neutropenia in a phase 3 study of bortezomib versus high-dose dexamethasone in
relapsed myeloma. Their preliminary data suggest bortezomib may reduce the thrombogenic potential of combination regimens via
inhibition of platelet function or other mechanism-specific effects on coagulation.
NBortezomib plus melphalan and prednisone for initial treatment of multiple myeloma.
San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS,
Dmoszynska A, Abdulkadyrov KM, Schots R, Jiang B, Mateos MV, Anderson KC, Esseltine DL, Liu K, Cakana A, van de Velde H,
Richardson PG; VISTA Trial Investigators.
N Engl J Med. 2008 Aug 28;359(9):906-17.
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http://www.ncbi.nlm.nih.gov/pubmed/18753647?ordinalpos=21&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
This phase 3 study compares the use of melphalan and prednisone with or without bortezomib in previously untreated patients with
myeloma who were ineligible for high-dose therapy. The authors find that bortezomib plus melphalan-prednisone was superior to
melphalan-prednisone alone.
NTreatment of myeloma are we making progress?
Durie BG.
N Engl J Med. 2008 Aug 28;359(9):964-6.
:
http://www.ncbi.nlm.nih.gov/pubmed/18753654?ordinalpos=20&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Comment on: N Engl J Med. 2008 Aug 28;359(9):906-17.
NNew drugs in multiple myeloma.
Berenson JR, Yellin O.
Curr Opin Support Palliat Care. 2008 Sep;2(3):204-10.
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http://www.ncbi.nlm.nih.gov/pubmed/18685422?ordinalpos=29&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_
DefaultReportPanel.Pubmed_RVDocSum
This review discusses new antimultiple myeloma arsenal, including combinations involving bortezomib, that has shown its worth in
both the relapsed/refractory and frontline setting.
www.myeloma.org
(800) 452 - CURE (2873)
NProspective comparison of subcutaneous versus intravenous administration of bortezomib in patients with
multiple myeloma.
Moreau P, Coiteux V, Hulin C, Leleu X, van de Velde H, Acharya M, Harousseau JL.
Haematologica. 2008 Sep 2. [Epub ahead of print.]
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http://www.ncbi.nlm.nih.gov/pubmed/18768528?ordinalpos=21&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_
DefaultReportPanel.Pubmed_RVDocSum
The authors assess the safety and efficacy of intravenous (IV) and subcutaneous (SC) administration of bortezomib and find SC
administration offers an alternative option to IV injection.
NThe combination of bortezomib, melphalan, dexamethasone and intermittent thalidomide is an effective
regimen for relapsed/refractory myeloma and is associated with improvement of abnormal bone metabolism
and angiogenesis.
Terpos E, Kastritis E, Roussou M, Heath D, Christoulas D, Anagnostopoulos N, Eleftherakis-Papaiakovou E, Tsionos K,
Croucher P, Dimopoulos MA.
Leukemia. 2008 Sep 4. [Epub ahead of print.]
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http://www.ncbi.nlm.nih.gov/pubmed/18769451?ordinalpos=25&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_
DefaultReportPanel.Pubmed_RVDocSum
The authors find that the combination of bortezomib, melphalan, dexamethasone and intermittent thalidomide is an active and well-
tolerated regimen for relapsed/refractory myeloma, affecting abnormal bone remodeling and angiogenesis.
NBortezomib inhibits maturation and function of osteoclasts from PBMCs of patients with multiple myeloma
by downregulating TRAF6.
Hongming H, Jian H.
Leuk Res. 2008 Sep 6. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18778854?ordinalpos=17&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_
DefaultReportPanel.Pubmed_RVDocSum
In an attempt to clarify the upstream molecular mechanism of bortezomib on osteoclastogenesis, the authors observe the inhibitory
effect of bortezomib on osteoclasts maturation and function from peripheral blood mononuclear cells of myeloma patients. They
conclude that bortezomib acts on osteoclastgenesis at low concentrations by interfering with TRAF6 production, which might prove to
be a potential strateg y for the treatment of myeloma bone disease.
NUpdated survival analyses after prolonged follow-up of the phase 2, multicenter CREST study of bortezomib
in relapsed or refractory multiple myeloma.
Jagannath S, Barlogie B, Berenson JR, Siegel DS, Irwin D, Richardson PG, Niesvizky R, Alexanian R, Limentani SA, Alsina M,
Esseltine DL, Anderson KC.
Br J Haematol. 2008 Sep 6. [Epub ahead of print.]
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http://www.ncbi.nlm.nih.gov/pubmed/18783399?ordinalpos=16&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_
DefaultReportPanel.Pubmed_RVDocSum
The authors present updated survival analyses after prolonged follow-up of a study that had previously demonstrated substantial activity
with two dose levels of bortezomib, alone or with dexamethasone, in relapsed or refractory myeloma.
NBortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature.
Argyriou AA, Iconomou G, Kalofonos HP.
Blood. 2008 Sept 7. [Epub ahead of print.]
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http://www.ncbi.nlm.nih.gov/pubmed/18574024?ordinalpos=62&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The authors review the pathogenesis, incidence, risk factors, diagnosis, characteristics and management of bortezomib-induced
peripheral neuropathy and highlight areas of future research to pursue.
www.myeloma.org
(800) 452 - CURE (2873)
NMultiple myeloma - an update on diagnosis and treatment.
Caers J, Vande Broek I, De Raeve H, Michaux L, Trullemans F, Schots R, Van Camp B, Vanderkerken K.
Eur J Haematol. 2008 Sep 13. [Epub ahead of print.]
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http://www.ncbi.nlm.nih.gov/pubmed/18637123?ordinalpos=16&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_
DefaultReportPanel.Pubmed_RVDocSum
This myeloma treatment update addresses the optimalization of different treatment options and schedules,
including the use of bortezomib.
NMany facets of bortezomib resistance/susceptibility.
Kumar S, Rajkumar SV.
Blood. 2008 Sep 15;112(6):2177-8.
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http://www.ncbi.nlm.nih.gov/pubmed/18779399?ordinalpos=9&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_
DefaultReportPanel.Pubmed_RVDocSum
No abstract available.
NPulse treatment with the proteasome inhibitor bortezomib inhibits osteoclast resorptive activity in clinically
relevant conditions.
Boissy P, Andersen TL, Lund T, Kupisiewicz K, Plesner T, Delaissé JM.
Leuk Res. 2008 Nov;32(11):1661-8. [Epub 2008 Apr 18.]
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http://www.ncbi.nlm.nih.gov/pubmed/18394701?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_
DefaultReportPanel.Pubmed_RVDocSum
The authors test bortezomib on cultured osteoclasts in conditions mimicking the pulse treatment used in the clinic, and demonstrate a
direct inhibition of osteoclasts by bortezomib in conditions relevant to treatment of myeloma.
NArsenic trioxide and 2-methoxyestradiol reduce beta-catenin accumulation after proteasome inhibition and
enhance the sensitivity of myeloma cells to Bortezomib.
Zhou L, Hou J, Fu W, Wang D, Yuan Z, Jiang H.
Leuk Res. 2008 Nov;32(11):1674-83. [Epub 2008 May 15.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18485479?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_
DefaultReportPanel.Pubmed_RVDocSum
The authors prove that beta-catenin protein levels are negatively associated with myeloma cells' sensitivity to bortezomib.
NBortezomib directly inhibits osteoclast function in multiple myeloma: implications into the management of
myeloma bone disease.
Terpos E.
Leuk Res. 2008 Nov;32(11):1646-7. [Epub 2008 Jul 9.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18614229?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_
DefaultReportPanel.Pubmed_RVDocSum
No abstract available.
www.myeloma.org
(800) 452 - CURE (2873)
(800)452-CURE (2873)
www.myeloma.org
www.myeloma.org
(800) 452 - CURE (2873)