|
|
Prepublished online as a Blood First Edition Paper on March 13, 2003; DOI 10.1182/blood-2002-09-2846.
Submitted October 8, 2002
Accepted February 24, 2003
A multi-centre phase-II trial of thalidomide in relapsed/refractory multiple myeloma reveals an adverse prognostic impact of advanced age
Linda R Mileshkin, James J Biagi, Paul Mitchell, Craig Underhill, Andrew Grigg, Richard Bell, Joe McKendrick, Peter Briggs, John F Seymour, Kate Lillie, Jennifer G Smith, Jerome B Zeldis, and H Miles Prince*
Department of Haematology, Peter MacCallum Cancer Institute, East Melbourne, VIC, Australia
Ludwig Oncology Department, Austin and Repatriation Medical Centre, Heidelberg, VIC, Australia
Border Medical Oncology, Albury, VIC, Australia
Department of Haematology, Royal Melbourne Hospital, Melbourne, VIC, Australia
Andrew Love Cancer Centre, The Geelong Hospital, Geelong, VIC, Australia
Oncology Department, Box Hill Hospital, Box Hill, VIC, Australia
Oncology Department, Monash Medical Centre, Clayton, VIC, Australia
Celgene Corporation, Warren, NJ, USA
Statistical Centre, Peter MacCallum Cancer Institute, East Melbourne, VIC, Australia
* Corresponding author; email: Miles.Prince{at}petermac.org.
Background: Patients with relapsed or refractory multiple myeloma have a poor outlook. Thalidomide has activity in a proportion, however criteria for predicting response have not been conclusively identified. Methods: We initiated a prospective multi-centre Phase-II trial in patients with relapsed/refractory myeloma using thalidomide up to maximum dose 800 mg/day. Interferon- -2B (1.5-3.0MU,SC,TIW) was added at week 12 if disease was responsive or stable. Patients intolerant of interferon continued thalidomide alone. Thalidomide +/- interferon was continued until disease progression. Objectives were to determine toxicity, response rate (RR), progression-free survival (PFS), overall survival (OS) and to elucidate relevant prognostic factors. Results: Seventy-five patients, with median age 64 (range 36-83), were enrolled. The median individual-maximum-tolerated dose of thalidomide was 600mg/day. 41% reached 800 mg/day. Overall RR was 28% with one complete response, and 55% stable disease (SD). The only predictor for response was age  65 (38% vs 17%;P=0.043). At 18 months median follow-up, the actuarial median PFS and OS were 5.5 and 14.6 months respectively. Multivariate analysis for OS demonstrated age >65 (median 9.2mo v >26mo;P=0.011), raised serum LDH (P=0.002), and raised serum creatinine (P=0.007) predicted inferior outcomes. Nineteen patients received interferon. 10 discontinued due to toxicity. Four of 12 patients who received >4 weeks interferon were converted from SD to partial response. Conclusions: Our findings confirm substantial activity of thalidomide in relapsed/refractory myeloma. Interferon may improve response in selected patients, but is often not tolerated. The inferior outcome demonstrated in those with the identified prognostic factors is important in planning management for these patients.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
Thalidomide, age, and future use in multiple myeloma
- Mohamad A. Hussein
Blood 2003 102: 2-3.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
N. D. Yildirim, M. Ayer, R. D. Kucukkaya, N. Alpay, O. Mete, M. N. Yenerel, A. S. Yavuz, and M. Nalcaci
Leukocytoclastic Vasculitis due to Thalidomide in Multiple Myeloma
Jpn. J. Clin. Oncol.,
September 1, 2007;
37(9):
704 - 707.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Mileshkin, D. Honemann, P. Gambell, M. Trivett, Y. Hayakawa, M. Smyth, V. Beshay, D. Ritchie, P. Simmons, A. D. Milner, et al.
Patients with multiple myeloma treated with thalidomide: evaluation of clinical parameters, cytokines, angiogenic markers, mast cells and marrow CD57+ cytotoxic T cells as predictors of outcome
Haematologica,
August 1, 2007;
92(8):
1075 - 1082.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. G. Richardson, C. Mitsiades, R. Schlossman, N. Munshi, and K. Anderson
New Drugs for Myeloma
Oncologist,
June 1, 2007;
12(6):
664 - 689.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Mileshkin, R. Stark, B. Day, J. F. Seymour, J. B. Zeldis, and H. M. Prince
Development of Neuropathy in Patients With Myeloma Treated With Thalidomide: Patterns of Occurrence and the Role of Electrophysiologic Monitoring
J. Clin. Oncol.,
September 20, 2006;
24(27):
4507 - 4514.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Zonder
Thrombotic Complications of Myeloma Therapy
Hematology,
January 1, 2006;
2006(1):
348 - 355.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Hiddemann, M. Kneba, M. Dreyling, N. Schmitz, E. Lengfelder, R. Schmits, M. Reiser, B. Metzner, H. Harder, S. Hegewisch-Becker, et al.
Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group
Blood,
December 1, 2005;
106(12):
3725 - 3732.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. R. Mileshkin, P. Gambell, V. Beshay, Y. Hayakawa, M. Smyth, M. Trivett, P. J. Simmons, A. Milner, J. B. Zeldis, and M. Prince
Increased Marrow CD57+ Cytotoxic T Cells Is a Powerful Prognostic Marker for Survival in Patients with Relapsed Multiple Myeloma (MM) Receiving Thalidomide.
Blood (ASH Annual Meeting Abstracts),
November 16, 2005;
106(11):
3486 - 3486.
[Abstract]
|
|
|
|
|
|
|
M. Duyvendak, M. Naunton, B. J Kingma, and J. R. Brouwers
Thalidomide-Associated Thrombocytopenia
Ann. Pharmacother.,
November 1, 2005;
39(11):
1936 - 1939.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. G. G. Richardson, B. Barlogie, J. Berenson, S. Singhal, S. Jagannath, D. Irwin, S. V. Rajkumar, T. Hideshima, H. Xiao, D. Esseltine, et al.
Clinical factors predictive of outcome with bortezomib in patients with relapsed, refractory multiple myeloma
Blood,
November 1, 2005;
106(9):
2977 - 2981.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Saunders
Overview of drug therapy for multiple myeloma
Journal of Oncology Pharmacy Practice,
September 1, 2005;
11(3):
83 - 100.
[Abstract]
[PDF]
|
|
|
|
|
|
|
H M. Prince, L. Mileshkin, A. Roberts, V. Ganju, C. Underhill, J. Catalano, R. Bell, J. F. Seymour, D. Westerman, P. J. Simmons, et al.
A Multicenter Phase II Trial of Thalidomide and Celecoxib for Patients with Relapsed and Refractory Multiple Myeloma
Clin. Cancer Res.,
August 1, 2005;
11(15):
5504 - 5514.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X.-Y. Pei, Y. Dai, M. Rahmani, W. Li, P. Dent, and S. Grant
The Farnesyltransferase Inhibitor L744832 Potentiates UCN-01-Induced Apoptosis in Human Multiple Myeloma Cells
Clin. Cancer Res.,
June 15, 2005;
11(12):
4589 - 4600.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. W. B. Jeffes, J. G. Zhang, N. Hoa, A. Petkar, C. Delgado, S. Chong, A. Obenaus, R. Sanchez, S. Khalaghizadeh, T. Khomenko, et al.
Antiangiogenic Drugs Synergize with a Membrane Macrophage Colony-Stimulating Factor-Based Tumor Vaccine to Therapeutically Treat Rats with an Established Malignant Intracranial Glioma
J. Immunol.,
March 1, 2005;
174(5):
2533 - 2543.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X.-Y. Pei, Y. Dai, and S. Grant
The small-molecule Bcl-2 inhibitor HA14-1 interacts synergistically with flavopiridol to induce mitochondrial injury and apoptosis in human myeloma cells through a free radical-dependent and Jun NH2-terminal kinase-dependent mechanism
Mol. Cancer Ther.,
December 1, 2004;
3(12):
1513 - 1524.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Chintagumpala, S. M. Blaney, L. R. Bomgaars, A. Aleksic, J. F. Kuttesch, R. A. Klenke, and S. L. Berg
Phase I and Pharmacokinetic Study of Thalidomide With Carboplatin in Children With Cancer
J. Clin. Oncol.,
November 1, 2004;
22(21):
4394 - 4400.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X.-Y. Pei, Y. Dai, and S. Grant
Synergistic Induction of Oxidative Injury and Apoptosis in Human Multiple Myeloma Cells by the Proteasome Inhibitor Bortezomib and Histone Deacetylase Inhibitors
Clin. Cancer Res.,
June 1, 2004;
10(11):
3839 - 3852.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Dai, X.-Y. Pei, M. Rahmani, D. H. Conrad, P. Dent, and S. Grant
Interruption of the NF-{kappa}B pathway by Bay 11-7082 promotes UCN-01-mediated mitochondrial dysfunction and apoptosis in human multiple myeloma cells
Blood,
April 1, 2004;
103(7):
2761 - 2770.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Dimopoulos, A. Anagnostopoulos, and D. Weber
Treatment of Plasma Cell Dyscrasias With Thalidomide and Its Derivatives
J. Clin. Oncol.,
December 1, 2003;
21(23):
4444 - 4454.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
