Thalidomide: study in hormone-resistant prostate cancer REVLIMID-lenalidomide-Actimid-discontinued due to no result is. To other forms of cancer-CLL and non-Hodgkin go further studies with good results so far.
This article is a few hours worked, search, translate, places etc. If you want to support us with a donation you can do so via this link, any amount no matter how small is welcome. This ensures you that cancer-up-to-date online can continue to exist
25 Celgene november 2011: source:
A phase III study with revlimid hormone resistant prostate cancer lenalidomide-for under the name-Actimid-is stopped by the producer because on mid-term evaluations of the study has found no positive effect on the survival time. Here the press release announcing this Celgene which stop. For myelodysplastic syndromes (MDS) chronic lymphocytic leukemia (CLL),, and non-Hodgkin Lymphoma (NHL) go through the studies. At the top of this article the recent press release. More information about revlimid-lenalidomide to other forms of cancer with positive results, so might be worthwhile to read the whole article or print.
Celgene is stop lenalidomide ping its Phase III trial or in patients with prostate cancer castrate-resistant (CRPC). The decision was based on the recommendation from the Data Monitoring Committee (DMC) that the study, called Mainsail, would not demonstrate a statistically significant effect against the primary endpoint or overall survival.
The compound is the Revlimidmarketed active ingredient in the drug. Halting the CRPC trial means that the firm's nearest hope for expanding its label now falls on studies in myelodysplastic syndromes (MDS), chronic lymphocytic leukemia (CLL), and non-Hodgkin's lymphoma (NHL).
"We have accepted this recommendation of the DMC and following formal notification and review of the analysis, physicians and patients, internationally, will be officially advised of this action," Celgene says. The double-blinded trial Mainsail was set up to evaluate the efficacy and safety of docetaxel and prednisone with or without lenalidomide.
The compound, branded as Revlimid in nearly 70 countries, is indicated in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. In Australia and New Zealand it is also sanctioned in combination with dexamethasone for the treatment of patients whose disease has progressed after one therapy.
In the U.S., Canada, several Latin American countries, Malaysia, and Israel, is marketed for transfusion-dependent anemia Revlimid due to low-or intermediate-1-risk MDS associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. Marketing applications are reportedly being evaluated in a number of other countries.
The molecule is currently under Phase III investigation as a treatment for other types of MDS, CLL, and NHL. Celgene also has a Phase II solid tumor trial that includes lenalidomide. It is reportedly in about 300 clinical trials around the globe.
Revlimid makes ups a significant portion of sales Celgene's. In the third quarter, the drug brought in $ 820 million, about 67% of total sales for that quarter, which reached almost $ 1.22 billion. During all of 2010, Revlimid sales increased approximately 44% to approximately $ 2.47 billion.
For Q3 2011, Revlimid sales grew 28% from Q2 2011. This was reportedly driven by continued market share gains, increased treatment duration, and geographic expansion. U.S. sales of $ 467 million and international sales or $ 353 million increased 25% and 32%, respectively, during Q3
20 May 2005: "source: Anticancer Drugs. 2003 Jun; 14 (5): 331-5. In the following phase I/II study from 2003 is already touted as an effective drug Thalidomide Kahler-Multiple Myeloma against gemestateerde Melanoma. and At ASCO 2005 his later studies presented with custom shapes of Thalidomide drugs under the name REVLIMID at MSD = Myelodyplastisch syndrome, precursor often of cancers in bone marrow disease of Waldenström blood or if forms of leukemia. and Kahler and There is now a phase III trial at Kahler-Multiple Myeloma and melanoma gemestasteerde under the name Thalidomide-REVLIMID and phase I/II trials prostate cancer ACTIMID under the name in breast cancer. and
The effect of Thalidomide seems so that the T cells = immune cells (immune system) stimulates and anti-angiogenetische (inhibits formation of new blood vessels) and/or anti-inflammatory effects or. And especially people with missing chromosome 5q31 advance seem to have with this medication. However the original Thalidomide gave quite a few side effects and to see new forms of Thalidomide as ACTIMID REVLIMID and exhibit less serious side effects. The side effects seem to be also collected with extra good nutrition and certain additional voedingsuppletie. Read this the story of Mr. HA as evidence that the combination with Thalidomide and vegetarian food with oily fish plus additional voedingsuppletie certain Kahler-Multiple Myeloma are under control and even his physical health very greatly improved the last year and a half years after the start with Thalidomide. Experience a wonderful story of someone who together with his wife and children with a complementary approach survives cancer with excellent taking life.
The abstract of some studies with Thalidomide, including in addition to the study with MSD a small-scale and limited but double-blind randomized study of Thalidomide in leprosy patients with remarkably good results and a study from 1986 in which Thalidomide significant positive effect in oral geniatele and canker sores and wounds Behcet syndrome known as, which stands out that once the administration of Thalidomide stops the condition backalso, what happened in the leprosy study.
Curr Hematol Rep. 2005 May; 4 (3): 182-5.
Lenalidomide (Revlimid, CC-5013) in myelodysplastic syndromes: is it any good?
Sekeres MA, List A.
H Lee Moffitt Cancer Center & Research Institute, University of South Florida, 12902 Magnolia Drive, Tampa, FL 33612-9497, USA.
The myelodysplasticsyndromes (MDS) can be divided into "early" and "advanced" disease by evaluation of prognostic variables such as the number of cytopenias, karyotype, and percentage or myeloblasts. Patients with an isolated interstitial deletion of chromosome 5q31 represent a distinct subset who may derive particular benefit from immunomodulatory drugs. Goals of therapy for early MDS focus on hematologic improvement and maximizing quality of life. Thalidomide, the prototype of the immunomodulatory drugs, yields major erythroid responses in some patients with early MDS, but dose-limiting toxicities neurologic limit its potential clinical benefit. Lenalidomide, a more potent and non-neurotoxic derivative, has shown promising results in early MDS, yielding hematologic improvement in almost half of patients, and transfusion independence with cytogenetic remissions in approximately two thirds of patients harboring the chromosome 5q31 deletion.
PMID: 15865869 [PubMed-in process]
Thalidomide analogs as emerging anti-cancer drugs.
Dredge K, Dalgleish From AG, Marriott Jb.
Division of Oncology, St George's Hospital Medical School, London, UK. kdredge@sghms.ac.uk
Recently, it has been demonstrated that a number of novel thalidomide analogs possess anti-cancer properties due to their T cell co-stimulatory, anti-angiogenic and/or anti-inflammatory effects. Based on such effects, a class or Immunomodulatory Drugs (IMiDs) thalidomide analogs known as have recently entered into phase I clinical trials for the treatment of a number of cancers. The lead IMiD CC-5013 (referred to clinically as REVIMID) is now entering phase III clinical trials for multiple myeloma and metastatic melanoma, while CC-is currently under investigation for (ACTIMID) in phase I/II and II trials for multiple myeloma and prostate cancer, respectively. The other group of compounds, classified as Selective Cytokine Inhibitory Drugs (SelCIDs), do not co-stimulate T cells, but have anti-inflammatory and anti-angiogenic properties. Moreover, a subset or SelCIDs has been found to possess direct anti-tumor activity both in vitro and in vivo. This mini review highlights the various mechanisms of action associated with these compounds and their subsequent clinical development. The enhanced efficacy and lower side-effect profiles of the thalidomide analogs in comparison to make the use of these agents very attractive as novel anti-cancer agents.
PMID: 12782937 [PubMed-indexed for MEDLINE]
Expert Opin Biol Ther. 2004 Dec; 4 (12): 1963-70.
Thalidomide-derived immunomodulatory drugs as therapeutic agents.
Galustian C, Labarthe MC, Bartlett JB, Dalgleish From AG.
St George's Hospital Medical School, Division of Oncology, Department of Cellular & Molecular Medicine, Cranmer Terrace, London SW17 0RE, UK,. cgalusti@sghms.ac.uk
Thalidomide, a drug originally used to treat morning sickness, was removed fromthe market place in the early 1960s after it was found to cause serious congenital birth defects. However, thalidomide has recently been investigated in a new light following its activity in a number of chronic diseases. Moreover, like thalidomide itself, its second-generation immunomodulatory drug (IMiD) analogues have been shown to act as powerful anticancer agents and are clearly active in the treatment of patients with relapsed multiple myeloma. These new drugs, in particular the second-generation IMiDs, lenalidomide (REVLIMID, CC-5013; Celgene Corp., NJ, USA) and CC-ACTIMID (for; Celgene Corp.), offer improvements on thalidomide (a first-generation IMiD) in terms of efficacy and safety in human studies. The key to the therapeutic potential of IMiDs lies in the fact that the drugs have multiple mechanisms of action, which may produce both anti-inflammatory and antitumour effects. These effects are probably contextual, depending both on the cell type and the stimulus involved. Mechanisms associated with IMiD activity include TNF-alpha-inhibitory, T cell costimulatory and antiangiogenic activities. Studies of the mechanisms of action of these drugs are ongoing and will facilitate the continued development of this class or compound in a number of diseases.
PMID: 15571458 [PubMed-in process]
Am J Trop Med Hyg. 2005 May; 72 (5): 518-526. Related Articles, Links A RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, CONTROLLED DOSE COMPARISON Or ERYTHEMA NODOSUM LEPROSUM Or THALIDOMIDE FOR TREATMENT. Villahermosa LG, Fajardo TT Jr, Abalos RM, MV Balagon, Tan EV, JP, Wittes J Cellona RV, Palmer, Thomas SD, Cooking KA, Walsh GP, Walsh DS. Leonard Wood Memorial Center for Leprosy Research (American Leprosy Foundation) Cebu City, The Philippines; Statistics Collaborative, Inc., Washington, District of Columbia; Celgene Corporation, Warren, New Jersey; Salamandra, Inc., Bethesda, Maryland; Dermatology Service, Eisenhower Army Medical Center, Fort Gordon, Georgia. In a randomized, double-blind, double-dummy controlled study, 22 men with erythema nodosum leprosum (ENL) received six capsules containing either 100 mg (group A, n = 12) or 300 mg (group B, n = 10) or thalidomide daily for one week. A six-week, four capsules per day taper followed, in which group A received 50 mg/day or thalidomide in weeks 2 and 3, then dummy capsules in weeks 4 through 7, while group B had gradual decrements every two weeks. Both regi man caused comparable improvement in 19 patients at day 7 (group A [12 or 12] versus group B [7 or 10]; P = 0.08), but slower tape ring in group B showed less re-emergence of ENL through week 7 (P = 0.02, versus group A). Most patients developed new lesions soon after stopping treatment. Slower tape ring from a higher initial thalidomide dose may improve clinical ENL responses, but high recurrence rates after Announces discontinuation indicates further assessment is needed to identify better tape ring regi man. PMID: 15891124 [PubMed-as suppliedby publisher]
Am J Trop Med Hyg. 2005 May; 72 (5): 518-526.
A RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, CONTROLLED DOSE COMPARISON OR ERYTHEMA NODOSUM LEPROSUM OR THALIDOMIDE FOR TREATMENT.
Villahermosa LG, Fajardo TT Jr, Abalos RM, MV Balagon, Tan EV, JP, Wittes J Cellona RV, Palmer, Thomas SD, Cooking KA, Walsh GP, Walsh DS.
Leonard Wood Memorial Center for Leprosy Research (American Leprosy Foundation) Cebu City, The Philippines; Statistics Collaborative, Inc., Washington, District of Columbia; Celgene Corporation, Warren, New Jersey; Salamandra, Inc., Bethesda, Maryland; Dermatology Service, Eisenhower Army Medical Center, Fort Gordon, Georgia.
In a randomized, double-blind, double-dummy controlled study, 22 men with erythema nodosum leprosum (ENL) received six capsules containing either 100 mg (group A, n = 12) or 300 mg (group B, n = 10) or thalidomide daily for one week. A six-week, four capsules per day taper followed, in which group A received 50 mg/day or thalidomide in weeks 2 and 3, then dummy capsules in weeks 4 through 7, while group B had gradual decrements every two weeks. Both regi man caused comparable improvement in 19 patients at day 7 (group A [12 or 12] versus group B [7 or 10]; P = 0.08), but slower tape ring in group B showed less re-emergence of ENL through week 7 (P = 0.02, versus group A). Most patients developed new lesions soon after stopping treatment. Slower tape ring from a higher initial thalidomide dose may improve clinical ENL responses, but high recurrence rates after Announces discontinuation indicates further assessment is needed to identify better tape ring regi man.
PMID: 15891124 [PubMed-as supplied by publisher]
Ann Intern Med. 1998 Mar 15; 128 (6): 443-50.
Comment in:
Ann Intern Med. 1998 Mar 15; 128 (6): 494-5.
Ann Intern Med. 1998 Nov 15; 129 (10): 836.
Thalidomide in the treatment of the mucocutaneous lesions or the Behcet syndrome. A randomized, double-blind, placebo-controlled trial.
Hamuryudan V, Mat C, Saip S, Ozyazgan Y, Siva A Yurdakul, S, Zwingenberger K, Yazici H.
Cerrahpasa Medical Faculty, Behcet's Syndrome Research Center, University of Istanbul, Turkey.
BACKGROUND: Recurrent oral and genital ulcers are the most frequent problem in the management or the Behcet syndrome. Uncontrolled experience suggests that thalidomide may help prevent recurrences of these ulcers.
OBJECTIVE: To determine the efficacy of two dosages thalidomide in the treatment of mucocutaneous lesions or the Behcet syndrome. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Specialist outpatient clinic for the Behcet syndrome in Turkey.
PATIENTS: 96 male patients with Behcet syndrome who had primarily mucocutaneous lesions without the major organ involvement.
INTERVENTION: Thalidomide, 100 mg/d or 300 mg/d, or placebo for 24 weeks.
MEASUREMENTS: Sustained absence orany oral and genital ulceration during treatment (complete response) and changes in the number or mucocutaneous lesions. An additional evaluation was done 4 weeks after treatment ended.
RESULTS: A complete response occurred in 2 of the 32 patients (6% [95% CI, 0.8% to 12.9%]) receiving thalidomide, 100 mg/d; in 5 of the 31 patients (16% [CI, 5.5% to 33.7%]) receiving thalidomide, 300 mg/d; and in none of the 32 patients (0% [CI, 0% to 10.9%]) receiving placebo (P = 0.031). The suppressive effect of thalidomide with either dosage was evident at 4 weeks for oral ulcers (P < 0.001) and at 8 weeks for genital ulcers (P < 0.001) and follicular lesions (P = 0.008). This effect persisted during treatment but diminished rapidly after treatment was discontinued. Both led to significant increases in the number dosages thalidomide or erythema nodosum lesions during the first 8 weeks of treatment (P = 0.03). Polyneuropathy developed in 4 patients (1 in the 100-mg/d group and 3 in the 300-mg/d group); in 3 of these patients, the condition was diagnosed after the trial had ended.
CONCLUSIONS: Thalidomide is effective for treating the oral and genital ulcers and follicular lesions or the Behcet syndrome. A dosage or 100 mg/d is as effective as a dosage or 300 mg/day.
Randomized Controlled Trial
PMID: 9499327 [PubMed-indexed for MEDLINE]
