E-DRUG: Thalidomide research?
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Dear colleagues
I would like to know the status of thalidomide research with reference to
AIDS and Leprosy treatment.
Thanks for your time.
--
K Valliappan
Annamalai University, India.
"K Valliappan" <kvalliappan@gmail.com>
E-DRUG: Thalidomide research? (2)
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Hello Valliappan,
Dark Remedy: The impact of Thalidomide and its revival as a vital medicine by Rock Brynner and Trent Stephens, is surely a must read for you as you are interested in the re-emergence of Thalidomide.
The book and numerous scholarly articles have established that in the current management of HIV/AIDS, thalidomide has not much role (it had initial promise in the management of aphthous and esophageal ulcers). However thalidomide has a significant role in the management of ENL and Multiple Scelrosis and other autoimmune conditions as a TNF-alpha inhibitor.
Jude Nwokike MPH
Jude Nwokike.
Health worker
Botswana National ARV program [MASA]
Botswana
Email monkiyke@yahoo.com
[Details added by moderator]
E-DRUG: Thalidomide research? (3)
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The book and numerous scholarly articles have established that in
the current management of HIV/AIDS, thalidomide has not much role
I was not aware that thalidomide's potential role in management of HIV-
related conditions (including I think KS) had been discounted, and I have
been unable to find any of the "numerous scholarly articles". Could
someone point me in the right direction?
Thanks
Chris
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Chris W. Green
Treatment Educator, Spiritia Foundation
Jakarta, Indonesia
Tel: +62 (21) 7279 7007 Fax: +62 (21) 726-9521
"Chris W. Green" <chrisg@rad.net.id>
E-DRUG:Thalidomide research? (4)
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I did a quick search on Pubmed
(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi). Below are some relevant
references from 1997 onwards. However, this first relatively new Lancet
article gives a good overview, as does the new article from British
Journal of Dermatology.
Franks ME, Macpherson GR, Figg WD. Thalidomide. Lancet. 2004 May
29;363(9423):1802-11.
Despite its history as a human teratogen, thalidomide is emerging as a
treatment for cancer and inflammatory diseases. Although the evolution
of its clinical application could not have been predicted from the
tragedy associated with its misuse in the past, its history serves as a
lesson in drug development that underscores the need to understand the
molecular pharmacology of a compound's activity, including associated
toxicities. Here, we summarise the applications for thalidomide with an
emphasis on clinical trials published over the past 10 years, and
consider our knowledge of the molecular pharmacology of the drug in the
context of clinical trial data, attempting to provide a mechanism-guided
understanding of its activity.
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Wu JJ, Huang DB, Pang KR, Hsu S, Tyring SK. Thalidomide: dermatological
indications, mechanisms of action and side-effects. Br J Dermatol. 2005
Aug;153(2):254-73.
Thalidomide was first introduced in the 1950s as a sedative but was
quickly removed from the market after it was linked to cases of severe
birth defects. However, it has since made a remarkable comeback for the
U.S. Food and Drug Administration-approved use in the treatment of
erythema nodosum leprosum. Further, it has shown its effectiveness in
unresponsive dermatological conditions such as actinic prurigo, adult
Langerhans cell histiocytosis, aphthous stomatitis, Behcet's syndrome,
graft-versus-host disease, cutaneous sarcoidosis, erythema multiforme,
Jessner-Kanof lymphocytic infiltration of the skin, Kaposi sarcoma,
lichen planus, lupus erythematosus, melanoma, prurigo nodularis,
pyoderma gangrenosum and uraemic pruritus. This article reviews the
history, pharmacology, mechanism of action, clinical uses and adverse
effects of thalidomide.
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Titles of some relevant articles from 1997. It seems that aphthous
ulcers are the main indication. However, in 2005 multiple myeloma is the
main research focus; this is a cancer also affecting HIV-positives.
1: Taiwo BO. Use of thalidomide in HIV infection. AIDS Read.
2001;11(10):511-3, 518-9, 523-4.
2: Shetty K. Thalidomide for recurrent aphthous ulcerations. HIV Clin.
2003 Summer;15(3):1, 4-6.
3: Birnkrant D. Thalidomide for aphthous ulcers in HIV infection. N
Engl J Med. 1997;337(15):1086-7.
4: Jacobson JM, Greenspan JS, Spritzler J, Fox L, Fahey JL, Jackson JB,
Chernoff M, Wohl DA, Pulvirenti JJ, Hooton TM, Shikuma C. Thalidomide in
low intermittent doses does not prevent recurrence of human
immunodeficiency virus-associated aphthous ulcers. J Infect Dis.
2001;183(2):343-346.
5: Jacobson JM, Greenspan JS, Spritzler J, Ketter N, Fahey JL, Jackson
JB, Fox L, Chernoff M, Wu AW, MacPhail LA, Vasquez GJ, Wohl DA.
Thalidomide for the treatment of oral aphthous ulcers in patients with
human immunodeficiency virus infection. National Institute of Allergy
and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med. 1997
May 22;336(21):1487-93.
6: Aweeka F, Trapnell C, Chernoff M, Jayewardene A, Spritzler J,
Bellibas SE, Lizak P, Jacobson J. Pharmacokinetics and pharmacodynamics
of thalidomide in HIV patients treated for oral aphthous ulcers: ACTG
protocol 251. AIDS Clinical Trials Group. J Clin Pharmacol. 2001
Oct;41(10):1091-7.
7: Jacobson JM, Spritzler J, Fox L, Fahey JL, Jackson JB, Chernoff M,
Wohl DA, Wu AW, Hooton TM, Sha BE, Shikuma CM, MacPhail LA, Simpson DM,
Trapnell CB, Basgoz N. Thalidomide for the treatment of esophageal
aphthous ulcers in patients with human immunodeficiency virus infection.
National Institute of Allergy and Infectious Disease AIDS Clinical
Trials Group. J Infect Dis. 1999 Jul;180(1):61-7.
8: Sharp M, Getty J, Klausner JD. Thalidomide use is associated with
weight gain in HIV-1-positive clients. J Acquir Immune Defic Syndr Hum
Retrovirol. 1997 Aug 15;15(5):392. No abstract available.
9: Ramirez-Amador VA, Esquivel-Pedraza L, Ponce-de-Leon S, Reyes-Teran
G, Gonzalez-Guevara M, Ponce-de-Leon S, Sierra-Madero JG. Thalidomide as
therapy for human immunodeficiency virus-related oral ulcers: a
double-blind placebo-controlled clinical trial. Clin Infect Dis. 1999
Apr;28(4):892-4.
10: Wohl DA, Aweeka FT, Schmitz J, Pomerantz R, Cherng DW, Spritzler J,
Fox L, Simpson D, Bell D, Holohan MK, Thomas S, Robinson W, Kaplan G,
Teppler H; National Institute of Allergy and Infectious Diseases AIDS
Clinical Trials Group 267. Safety, tolerability, and pharmacokinetic
effects of thalidomide in patients infected with human immunodeficiency
virus: AIDS Clinical Trials Group 267. J Infect Dis. 2002 May
1;185(9):1359-63.
11: Mercie P, Viallard JF, Cipriano C, Tchamgoue S, Leng B, Pellegrin
JL. Aphtous stomatitis in a patient with Behcet's disease and HIV was
associated with an increased HIV load. Clin Exp Rheumatol. 2002
Jul-Aug;20(4 Suppl 26):S54. No abstract available.
12: Surawicz CM. Thalidomide for AIDS diarrhea? Am J Gastroenterol.
1997 Dec;92(12):2312-3.
13: Maurer T, Poncelet A, Berger T. Thalidomide treatment for prurigo
nodularis in human immunodeficiency virus-infected subjects: efficacy
and risk of neuropathy. Arch Dermatol. 2004 Jul;140(7):845-9.
14: Aboulafia DM. Thalidomide-based treatment for HIV-associated
multiple myeloma: a case report. AIDS Read. 2003 Aug;13(8):383-9.
Review.
15: Nasca MR, Micali G, Cheigh NH, West LE, West DP. Dermatologic and
nondermatologic uses of thalidomide. Ann Pharmacother. 2003
Sep;37(9):1307-20. Review.
16: Jung CP, Emmerich B, Goebel FD, Bogner JR. Successful treatment of
a patient with HIV-associated multicentric Castleman disease (MCD) with
thalidomide. Am J Hematol. 2004 Mar;75(3):176-7.
17: Alfadley A, Al-Hawsawi K, Thestrup-Pedersen K, Al-Aboud K.
Treatment of prurigo nodularis with thalidomide: a case report and
review of the literature. Int J Dermatol. 2003 May;42(5):372-5. Review.
No abstract available.
18: Pantanowitz L, Dezube BJ. Editorial comment: multiple myeloma and
HIV infection--causal or casual coincidence?
AIDS Read. 2003 Aug;13(8):386-7. Review. No abstract available.
19: Herranz P, Pizarro A, De Lucas R, Arribas JR, Garcia-Tobaruela A,
Pena JM, Casado M. Treatment of AIDS-associated prurigo nodularis with
thalidomide. Clin Exp Dermatol. 1998 Sep;23(5):233-5.
20. Larson ML, Enschede SH, Gregory SA, Kaplan L. HIV-related Lymphoma
Treated With Maintenance Thalidomide. Clin Adv Hematol Oncol. 2005
Mar;3(3):231-4.
21: Maurer T, Poncelet A, Berger T. Thalidomide treatment for prurigo
nodularis in human immunodeficiency virus-infected subjects: efficacy
and risk of neuropathy. Arch Dermatol. 2004 Jul;140(7):845-9.
This is an older article:
Gunzler V. Thalidomide in human immunodeficiency virus (HIV) patients. A
review of safety considerations. Drug Saf. 1992 Mar-Apr;7(2):116-34.
The sedative thalidomide was withdrawn from the market 30 years ago
because of its teratogenic and neurotoxic adverse effects. The compound
was later discovered to be extremely effective in the treatment of
erythema nodosum leprosum, a complication of lepromatous leprosy. This
effect is probably due to a direct influence on the immune system,
because thalidomide possesses no antibacterial activity. The compound is
presently used as an experimental drug in the treatment of a variety of
diseases with an autoimmune character, including recurrent aphthosis of
nonviral and nonfungal origin in human immunodeficiency virus (HIV)
patients. This article reviews the most important chemical and
pharmacokinetic properties of thalidomide. The possible mechanisms of
the nonsedative effects of thalidomide with respect to the safety of its
use in HIV patients are discussed. Because the mechanism of the
immunomodulatory effect of thalidomide is unknown, the possibility that
the administration of this compound will accelerate the deterioration of
the immunological status of HIV patients cannot be excluded. Clinical
evidence suggests that thalidomide may aggravate the condition of
patients with preexisting peripheral neuropathy. Hypersensitivity
reactions to thalidomide may occur more frequently in HIV patients than
in other patient groups. Because of the teratogenic activity of
thalidomide, reliable contraception must be provided to female patients
of childbearing age. Before the introduction of thalidomide therapy to
an HIV patient presenting with oral ulcers, a fungal or viral origin of
the lesions should be excluded. Thalidomide should not be used in
patients with preexisting HIV-related peripheral polyneuropathy,
polyradiculopathy or encephalopathy. In patients experiencing a complete
remission, the discontinuation of thalidomide treatment and its
reintroduction in the case of a relapse are preferable to maintenance
therapy.
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Kirsten Myhr
Lillogt 5G
0484 Oslo, Norway
Tel +47 22 09 00 43
Mobile +47 416 38 747
myhr@online.no