Skip to main content
Log in

Potential Novel Uses of Thalidomide

Focus on Palliative Care

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Thalidomide, after being banned from the market in the early 1960s because of the worldwide teratogenesis disaster, is currently being rediscovered because of its multiple therapeutic effects in various serious diseases and symptoms. Original studies examined the anxiolytic, mild hypnotic, anti-emetic and adjuvant analgesic properties of this drug. Subsequently, thalidomide was found to be highly effective in managing the cutaneous manifestations of leprosy (erythema nodosum leprosum) and even to be superior to aspirin (acetylsalicylic acid) in controlling leprosy-associated fever. Recent research shows promising results with thalidomide in patients with progressive bodyweight loss related to advanced cancer and HIV infection. Thalidomide therapy of diseases such as tuberculosis, sarcoidosis, aphthous ulcers in HIV syndrome and Behcet’s disease, rheumatoid arthritis, multiple myeloma, graft-versus-host disease, pyoderma gangrenosum, inflammatory bowel disease, Sjögren’s syndrome, lupus erythematosus and a variety of solid tumours is currently being explored.

Furthermore, in preliminary studies, thalidomide has been found to be effective in several syndromes related to advanced cancer, such as the cancer cachexia syndrome, chronic nausea, insomnia, profuse sweating and pain. Whether thalidomide has a therapeutic effect on neoplastic fever has yet to be elucidated. These intriguing features make the use of the drug potentially attractive for palliative care. In addition, by a distinct mechanism of action compared with most other drugs, thalidomide offers the possibility of combined treatment with other agents with non-overlapping toxicities.

The mechanism of action of thalidomide is probably based on the suppression of tumour necrosis factor-α and the modulation of interleukins. However, it is not possible to identify a single dominant mechanism, since the action of cytokines and the effect of thalidomide appear to be complex. This review article discusses the original uses and teratogenic effects of thalidomide within its historical context and, linking recent research at the molecular level with clinical findings, aims to provide the reader with insight into the current understanding of its biological actions, toxicities and potential benefits.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Martindale W. The extra pharmacapoeia. London: Pharmaceutical Press, 1977

    Google Scholar 

  2. McBride WG. Thalidomide and congenital abnormalities [editorial]. Lancet 1961; II: 1358

    Article  Google Scholar 

  3. Lenz W. Thalidomide and congenital abnormalities [editorial]. Lancet 1962; I: 45

    Article  Google Scholar 

  4. Woodcock J. Supervisory review of NDA 20-785. Washington (DC): Food and Drug Administration, 1998

    Google Scholar 

  5. Thalidomide: potential benefits and risks: open public scientific workshop. Washington (DC): National Institutes of Health, 1997

  6. Alstead S, MacArthur JG, Thomson TJ, et al. Clinical pharmacology. London: Baillire Tindall & Cassell, 1969

    Google Scholar 

  7. Wolstenholme G, Porter R, editors. Drug responses in man. Symposium on drug responses in man. London: Churchill, 1966

    Google Scholar 

  8. Link to Thalidomide’s approved label: THALODMID (thalidomide) capsules. Washington (DC): US Food and Drug Administration/CTEP, 1998

  9. Raje N, Anderson K. Thalidomide: a revival story. N Engl J Med 1999; 341: 1606–8

    Article  PubMed  CAS  Google Scholar 

  10. Celgene Corporation. Thalomid (thalidomide) STEPS (System for Thalidomide Education and Prescribing Safety) folder. Warren (NJ): Celgene Corporation, 1998

    Google Scholar 

  11. Lutwak-Mann C, Schmid K, Keberle H. Thalidomide in rabbit semen. Nature 1967; 214: 1018–20

    Article  PubMed  CAS  Google Scholar 

  12. Schumacher H, Smith RL, Williams RT. The metabolism of thalidomide: the fate of thalidomide and some of its hydrolysis products in various species. Br J Pharmacol 1965; 25: 324–37

    CAS  Google Scholar 

  13. Shannon EJ, Sandoval F, Krahenbuhl JL. Hydrolysis of thalidomide abrogates its ability to enhance mononuclear cell synthesis of IL-2 as well as its ability to suppress the synthesis of TNF-alpha. Immunopharmacology 1997; 36: 9–15

    Article  PubMed  CAS  Google Scholar 

  14. Bauer KS, Dixon SC, Figg WD. Inhibition of angiogenesis by thalidomide requires metabolic activation, which is species-dependent. Biochem Pharmacol 1998; 55: 1827–34

    Article  PubMed  CAS  Google Scholar 

  15. Zwingenberger K, Wendt S. Immunomodulation by thalidomide: systematic review of the literature and of unpublished observations. J Inflamm 1995; 46: 177–211

    PubMed  CAS  Google Scholar 

  16. Sampaio EP, Sarno EN, Galilly R, et al. Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes. J Exp Med 1991; 173: 699–703

    Article  PubMed  CAS  Google Scholar 

  17. Moreira AL, Sampaio EP, Zmuidzinas A, et al. Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. J Exp Med 1993; 177: 1675–80

    Article  PubMed  CAS  Google Scholar 

  18. Rowland TL, McHugh SM, Deighton J, et al. Differential regulation by thalidomide and dexamethasone of cytokine expression in human peripheral blood mononuclear cells. Immunopharmacology 1998; 40: 11–20

    Article  PubMed  CAS  Google Scholar 

  19. Huizinga TW, Dijkmans BA, van der Velde EA, et al. An open study of pentoxyfylline and thalidomide as adjuvant therapy in the treatment of rheumatoid arthritis. Ann Rheum Dis 1996; 55: 833–6

    Article  PubMed  CAS  Google Scholar 

  20. Moreira AL, Tsenova-Berkova L, Wang J, et al. Effect of cytokine modulation by thalidomide on the granulomatous response in murine tuberculosis. Tuber Lung Dis 1997; 78: 47–55

    Article  PubMed  CAS  Google Scholar 

  21. Sampaio EP, Kaplan G, Miranda A, et al. The influence of thalidomide on the clinical and immunologic manifestation of erythema nodosum leprosum. J Infect Dis 1993; 168: 408–14

    Article  PubMed  CAS  Google Scholar 

  22. Moller DR, Wysocka M, Greenlee BM, et al. Inhibition of IL-12 production by thalidomide. J Immunol 1997; 159: 5157–61

    PubMed  CAS  Google Scholar 

  23. Haslett PA, Corral LG, Albert M, et al. Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset. J Exp Med 1998; 187: 1885–92

    Article  PubMed  CAS  Google Scholar 

  24. Zhu J, Deng GM, Diab A, et al. Thalidomide prolongs experimental autoimmune neuritis in Lewis rats. Scand J Immunol 1998; 48: 397–402

    Article  PubMed  CAS  Google Scholar 

  25. Nogueira AC, Neubert R, Helge H, et al. Thalidomide and the immune system. 3. Simultaneous up-and down-regulation of different integrin receptors on human white blood cells. Life Sci 1994; 55: 77–92

    Article  PubMed  CAS  Google Scholar 

  26. Neubert R, Nogueira AC, Neubert D. Thalidomide and the immune system. 2. Changes in receptors on blood cells of a healthy volunteer. Life Sci 1992; 51: 2107–16

    Article  PubMed  CAS  Google Scholar 

  27. Haslett P, Hempstead M, Seidman C, et al. The metabolic and immunologic effects of short-term thalidomide treatment of patients infected with the human immunodeficiency virus. AIDS Res Hum Retroviruses 1997; 13: 1047–54

    Article  PubMed  CAS  Google Scholar 

  28. Jacobson JM, Greenspan JS, Spritzler J, et al. 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 [see comments]. N Engl J Med 1997; 336: 1487–93

    CAS  Google Scholar 

  29. Sampaio EP, Moraes MO, Nery JA, et al. Pentoxifylline decreases in vivo and in vitro tumour necrosis factor-alpha (TNF-alpha) production in lepromatous leprosy patients with erythema nodosum leprosum (ENL). Clin Exp Immunol 1998; 111: 300–8

    Article  PubMed  CAS  Google Scholar 

  30. Goldberg RM, Loprinzi CL, Mailliard JA, et al. Pentoxifylline for treatment of cancer anorexia and cachexia? Arandomized, double-blind, placebo-controlled trial. J Clin Oncol 1995; 13: 2856–9

    PubMed  CAS  Google Scholar 

  31. B ruera ED, Roca E, Cedaro L, et al. Improved control of chemotherapy-induced emesis by the addition of dexamethasone to metoclopramide in patients resistantto metoclopramide. Cancer Treat Rep 1983; 67: 381–3

    CAS  Google Scholar 

  32. Moertel CG, Schutt AJ, Reitemeier RJ, et al. Corticosteroid therapy of preterminal gastrointestinal cancer. Cancer 1974; 33: 1607–9

    Article  PubMed  CAS  Google Scholar 

  33. Shannon EJ, Sandoval F. Thalidomide increases the synthesis of IL-2 in cultures of human mononuclear cells stimulated with Concanavalin-A, Staphylococcal enterotoxin A, and purified protein derivative. Immunopharmacology 1995; 31: 109–16

    Article  PubMed  CAS  Google Scholar 

  34. Ostraat O, Riesbeck K, Qi Z, et al. Thalidomide prolonged graft survival in a rat cardiac transplant model but had no inhibitory effect on lymphocyte function in vitro. Transplant Immunol 1996; 4: 117–25

    Article  CAS  Google Scholar 

  35. Fernandez LP, Schlegal PG, Baker J, et al. Does thalidomide affect IL-2 response and production? Exp Hematol 1995; 23(9): 978–85

    PubMed  CAS  Google Scholar 

  36. McHugh SM, Rifkin IR, Deighton J, et al. The immunosuppressive drug thalidomide induces T helper cell type 2 (Th2) and concomitantly inhibits Th1 cytokine production in mitogen-and antigen-stimulated human peripheral blood mononuclear cell cultures. Clin Exp Immunol 1995; 99(2): 160–7

    Article  PubMed  CAS  Google Scholar 

  37. Malaviya R, Ikeda T, Ross E, et al. Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-alpha. Nature 1996; 381: 77–80

    Article  PubMed  CAS  Google Scholar 

  38. Gordon JR, Galli SJ. Mast cells as a source of both preformed and immunologically inducible TNF-alpha/cachectin. Nature 1990; 346: 274–6

    Article  PubMed  CAS  Google Scholar 

  39. Dunzendorfer S, Schratzberger P, Reinisch N, et al. Effects of thalidomide on neutrophil respiratory burst, chemotaxis, and transmigration of cytokine-and endotoxin-activated endothelium. Naunyn Schmiedebergs Arch Pharmacol 1997; 356: 529–35

    Article  PubMed  CAS  Google Scholar 

  40. D’Amato RJ, Loughnan MS, Flynn E, et al. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A 1994; 91: 4082–5

    Article  PubMed  Google Scholar 

  41. Kruse FE, Joussen AM, Rohrschneider K, et al. Thalidomide inhibits corneal angiogenesis induced by vascular endothelial growth factor. Graefes Arch Clin Exp Ophthalmol 1998; 236: 461–6

    Article  PubMed  CAS  Google Scholar 

  42. Gutman M, Szold A, Ravid A, et al. Failure of thalidomide to inhibit tumor growth and angiogenesis in vivo. Anticancer Res 1996; 16: 3673–7

    PubMed  CAS  Google Scholar 

  43. Lewis JJ. An introduction to pharmacology. Edinburgh: E. & S. Livingstone, 1960

    Google Scholar 

  44. Barr Brown, RW, Hamilton-Hislop HG, Pritchard JG. A comparative clinical trial in the elderly of Distaval, Doriden, and Welldorm, three non-barbiturate hypnotics. Br J Clin Pract 1962; 16: 342–7

    Google Scholar 

  45. Hoffman W, Grospietsch G, Kuhn W. Genital malformations in thalidomide-damaged girls. Gerburtsch u Frauenheilk 1976; 36: 1066–70

    Google Scholar 

  46. Eddy NB, Friebel H, Hahn KJ, et al. Codeine and its alternates for pain and cough relief. 2. Alternates for pain relief. Bull World Health Organ 1969; 40: 1–53

    PubMed  CAS  Google Scholar 

  47. Paulus W, Keymer R. Detection of contergan and doriden, especially in cadavers. Arch Toxicol 1963; 20: 38–43

    Article  Google Scholar 

  48. Horstmann W. Reference to central nervous system damage within the context of thalidomide embryopathy: pathologic-anatomic, electroencephalographic and neurologic findings. Eur J Pediatr 1966; 96: 291–307

    CAS  Google Scholar 

  49. Iyer CG, Languillon J, Ramanujam K, et al. WHO co-ordinated short-term double-blind trial with thalidomide in the treatment of acute lepra reactions in male lepromatous patients. Bull World Health Organ 1971; 45: 719–32

    PubMed  CAS  Google Scholar 

  50. Sheskin J. Thalidomide in the treatment of lepra reactions. J Clin Pharmacol Ther 1965; 6: 303–6

    CAS  Google Scholar 

  51. Murphy PG, Borthwick LS, Johnston RS, et al. Nature of the retrograde signal from injured nerves that induces interleukin-6 mRNA in neurons. J Neuroscience 1999; 19: 3791–800

    CAS  Google Scholar 

  52. Marx GM, Levi JA, Bell DR, et al. A phase I/II trial of thalidomide as an anti-angiogenic agent in the treatment of advanced cancer [abstract 1751]. Proc Annu Meet Am Soc Clin Oncol 1999; 18: 454a

    Google Scholar 

  53. Eisen T, Boshoff C, Mak I, et al. Continous low dose thalidomide: a phase II study in advanced melanoma, renal cell, ovarian and breast cancer. Br J Cancer 2000; 82(4): 812–7

    Article  PubMed  CAS  Google Scholar 

  54. Long G, Vredenburgh J, Rizzieri DA, et al. Pilot trial of thalidomide post-autologous peripheral blood progenitor cell transplantation (PBPC) in patients with metastatic breast cancer [abstract 697]. Proc Annu Meet Am Soc Clin Oncol 1998; 17: 181a

    Google Scholar 

  55. Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999; 341: 1565–71

    Article  PubMed  CAS  Google Scholar 

  56. Olson KB, Hall TC, Horton J, et al. Thalidomide (N-phthaloylglutamimide) in the treatment of advanced cancer. Clin Pharmacol Ther 1965; 6: 292–7

    PubMed  CAS  Google Scholar 

  57. Minchinton AI, Fryer KH, Wendt KR, et al. The effect of thalidomide on experimental tumors and metastases. Anticancer Drugs 1996; 7: 339–43

    Article  PubMed  CAS  Google Scholar 

  58. Browne WL, Wilson WR, Baguley BC, et al. Suppression of serum tumour necrosis factor-alpha by thalidomide does not lead to reversal of tumour vascular collapse and anti-tumour activity of 5,6-dimethylxanthenone-4-acetic acid. Anticancer Res 1998; 18: 4409–13

    PubMed  CAS  Google Scholar 

  59. DiPaolo JA. Effect of thalidomide on a variety of transplantable tumors. Cancer Chemother Rep 1963; 29: 99–102

    PubMed  CAS  Google Scholar 

  60. Grabstald H, Golbey R. Clinical experiences with thalidomide in patients with cancer. Clin Pharmacol Ther 1965; 6: 298–302

    PubMed  CAS  Google Scholar 

  61. Braera E, Neumann CM, Pituskin E, et al. Thalidomide in patients with cachexia due to terminal cancer: preliminary report. Ann Oncol 1999; 10: 857–9

    Article  Google Scholar 

  62. Gutierrez-Rodriguez, O. Thalidomide. A promising new treatment for rheumatoid arthritis. Arthritis Rheum 1984; 27: 1118–21

    CAS  Google Scholar 

  63. Waters MF. An internally-controlled double blind trial of thalidomide in severe erythema nodosum leprosum. Leprosy Rev 1971; 42: 26–42

    PubMed  CAS  Google Scholar 

  64. Opromolla DV, Lima LS, Marques MB. Thalidomide in acute symptoms in leprosy (erythema nodosum or multiforme). Hospital (Rio J) 1966; 69: 827–44

    CAS  Google Scholar 

  65. Chrousos GP. The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med 1995; 332: 1351–62

    Article  PubMed  CAS  Google Scholar 

  66. Shannon EJ, Miranda RO, Morales MJ, et al. Inhibition of de novo IgM antibody synthesis by thalidomide as a relevant mechanism of action in leprosy. Scand J Immunol 1981; 13: 553–62

    Article  PubMed  CAS  Google Scholar 

  67. Gehanno P, Barry B, Depondt J, et al. Mouth and pharyngeal hyperalgesic syndromes in AIDS. Ann Otolaryngol Chir Cervicofac 1990; 107: 311–3

    PubMed  CAS  Google Scholar 

  68. Torras H, Lecha M, Mascaro JM. Thalidomide in the treatment of aphthosis and Behcet’s disease. 4 years’ experience. Med Cutan Ibero Lat Am 1982; 10: 103–12

    CAS  Google Scholar 

  69. Genvo MF, Faure M, Thivolet J. Treatment of aphthosis with thalidomide and with colchicine. Dermatologica 1984; 168: 182–8

    Article  PubMed  CAS  Google Scholar 

  70. Klausner JD, Makonkawkeyoon S, Akarasewi P, et al. The effect of thalidomide on the pathogenesis of human immunodeficiency virus type 1 and M. tuberculosis infection. J Acquir Immune Defic Syndr Hum Retrovirol 1996; 11: 247–57

    Article  CAS  Google Scholar 

  71. Field EO, Gibbs JE, Tucker DF, et al. Effect of thalidomide on the graft versus host reaction. Nature 1966; 211: 1308–10

    Article  PubMed  CAS  Google Scholar 

  72. Rovelli A, Arrigo C, Nesi F, et al. The role of thalidomide in the treatment of refractory chronic graft-versus-host disease following bone marrow transplantation in children. Bone Marrow Transplant 1998; 21: 577–81

    Article  PubMed  CAS  Google Scholar 

  73. Vogelsang GB, Fanner ER, Hess AD, et al. Thalidomide for the treatment of chronic graft-versus-host disease. N Engl J Med 1992; 326: 1055–8

    Article  PubMed  CAS  Google Scholar 

  74. Chao NJ, Parker PM, Niland JC, et al. Paradoxical effect of thalidomide prophylaxis on chronic graft-vs.-host disease. Biol Blood Marrow Transplant 1996; 2: 86–92

    PubMed  CAS  Google Scholar 

  75. Gutierrez-Rodriguez O, Starusta-Bacal P, Gutierrez-Montes O. Treatment of refractory rheumatoid arthritis: the thalidomide experience. J Rheum 1989; 16: 158–63

    PubMed  CAS  Google Scholar 

  76. Wolkenstein P, Latarjet J, Roujeau JC, et al. Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis. Lancet 1998; 352: 1586–9

    Article  PubMed  CAS  Google Scholar 

  77. Sateia MJ, Silberfarb PM. Sleep. In: Doyle D, Hanks GW, MacDonald N, editors. Oxford textbook of palliative medicine. Oxford: Oxford University Press, 1998

    Google Scholar 

  78. Bruera E, Fainsinger RL, Schoeller T, et al. Rapid discontinuation of hypnotics in terminal cancer patients: a prospective study. Ann Oncol 1996; 7: 855–6

    Article  PubMed  CAS  Google Scholar 

  79. Politi P, Reboredo G, Losso M, et al. Phase I trial of thalidomide in AIDS-related kaposi sarcoma (ks) [abstract 161]. Proc Annu Meet Am Soc Clin Oncol 1998; 17: 41a

    Google Scholar 

  80. Neuenschwander H, Bruera E. Asthenia-cachexia. In: Bruera E, Higginson I, editors. Cachexia-anorexia in cancer patients. Oxford: Oxford University Press, 1996: 57–75

    Google Scholar 

  81. Billingsly KG, Alexander HR. The pathophysiology of cachexia in advanced cancer and AIDS. In: Bruera E, Higginson I, editors. Cachexia-anorexia in cancer patients. Oxford: Oxford University Press, 1996: 1–22

    Google Scholar 

  82. Gagnon B, Bruera E. Areview of the drug treatment of cachexia associated with cancer. Drugs 1998; 55: 675–88

    Article  PubMed  CAS  Google Scholar 

  83. Fong Y, Moldawer LL, Marano M, et al. Cachectin/TNF or IL-1 alpha induces cachexia with redistribution of body proteins. Am J Physiol 1989; 256: R659–65

    PubMed  CAS  Google Scholar 

  84. Plata-Salaman, CR, Borkoski JP. Interleukin-8 modulates feeding by direct action in the central nervous system. Am J Physiol 1993; 265: R877–82

    PubMed  CAS  Google Scholar 

  85. Leon LR, White AA, Kluger MJ. Role of IL-6 and TNF in thermoregulation and survival during sepsis in mice. Am J Physiol 1998; 275: R269–77

    PubMed  CAS  Google Scholar 

  86. Tamura S, Ouchi KF, Mori K, et al. Involvement of human interleukin 6 in experimental cachexia induced by human uterine cervical carcinoma xenograft. Clin Cancer Res 1995; 11: 1353–8

    Google Scholar 

  87. Pereira J, Bruera E. Chronic nausea. In: Bruera E, Higginson I, editors. Cachexia-anorexia in cancer patients. Oxford: Oxford University Press, 1996: 112–19

    Google Scholar 

  88. Traldi A, Vaccari GL, Davoli G. Use of imide of N-phthalylglutamic acid (thalidomide) in the symptomatic therapy of vomiting of many patients with malignant neoplasms or caused by administration of mechlorethamine HCl. Cancro 1965; 18: 336–41

    PubMed  CAS  Google Scholar 

  89. Bruera E, Ernst S, Hagen N, et al. Effectiveness of megestrol acetate in patients with advanced cancer: a randomized, double-blind, crossover study. Cancer Prev Control 1998; 2: 74–8

    PubMed  CAS  Google Scholar 

  90. Tisdale MJ. Inhibition of lipolysis and muscle protein degradation by EPA in cancer cachexia. Nutrition 1996; 12Suppl. 1: S31–3

    Article  PubMed  CAS  Google Scholar 

  91. Maltin CA, Delday MI, Watson JS, et al. Clenbuterol, a beta-adrenoreceptor agonist, increases muscle strength in orthopaedic patients. Clin Sci 1993; 84: 651–4

    PubMed  CAS  Google Scholar 

  92. Burman R, Chamberlain J. The assessment of nutritional status, caloric intake, and appetite in patients with advanced cancer. In: Bruera E, Higginson I, editors. Cachexia-anorexia in cancer patients. Oxford: Oxford University Press, 1996: 34–49

    Google Scholar 

  93. Dinarello CA, Wolff SM. Molecular basis of fever in humans. Am J Med 1982; 72: 799–819

    Article  PubMed  CAS  Google Scholar 

  94. Brendzten KL, Baek D, Berild H, et al. Demonstration of circulating leukocytic pyrogen/interleukin 1 during fever [letter]. N Engl J Med 1984; 310: 596

    Google Scholar 

  95. Schroder JM, Gibbels E. Unmyelinated nerve fibers in senile nerves and in late thalidomide neuropathy: a quantitative electron microscopic study. Acta Neuropathologica 1977; 39: 271–80

    Article  PubMed  CAS  Google Scholar 

  96. Deaner P. Thalidomide for distressing night sweats in advanced malignant disease [letter]. Palliat Med 1998; 12: 208–9

    Article  PubMed  CAS  Google Scholar 

  97. Calder K, Bruera E. Thalidomide for night sweats in patients with advanced cancer [letter]. Palliat Med 2000; 14(1): 77–8

    Article  PubMed  CAS  Google Scholar 

  98. Foley KM. The treatment of cancer pain. N Engl J Med 1985; 313: 84–95

    Article  PubMed  CAS  Google Scholar 

  99. Bruera E, MacMillan K, Hanson J, et al. The Edmonton staging system for cancer pain: preliminary report. Pain 1989; 37: 203–9

    Article  PubMed  CAS  Google Scholar 

  100. Ebadi M, Bashir RM, Heidrick ML, et al. Neurotrophins and their receptors in nerve injury and repair. Neurochem Int 1997; 30: 347–74

    Article  PubMed  CAS  Google Scholar 

  101. DeLeo JA, Colburn RW, Nichols M, et al. Interleukin-6 mediated hyperalgesia/allodynia and increased spinal IL-6 expression in a rat mononeuropathy model. J Interferon Cytokine Res 1996; 16: 695–700

    Article  PubMed  CAS  Google Scholar 

  102. Sommer C, Marziniak M, Myers RR. The effect of thalidomide treatment on vascular pathology and hyperalgesia caused by chronic constriction injury of rat nerve. Pain 1998; 74: 83–91

    Article  PubMed  CAS  Google Scholar 

  103. Ringheim GE, Burgher KL, Heroux JA. Interleukin-6 mRNA expression by cortical neurons in culture: evidence for neuronal sources of interleukin-6 production in the brain. J Neuroimmunol 1997; 63: 113–23

    Article  Google Scholar 

  104. Bourde O, Kiefer R, Toyka KV, et al. Quantification of interleukin-6 mRNA in wallerian degeneration by competitive reverse transcription polymerase chain reaction. J Neuroimmunol 1999; 69: 135–40

    Google Scholar 

  105. Shin HC, Oh SJ, Jung SC, et al. Differential modulation of short and long latency sensory responses in the Si cortex by IL-6. Neuroreport 1997; 8: 2841–4

    Article  PubMed  CAS  Google Scholar 

  106. Rauen HM. Are thalidomide and its biological metabolites vitamin antagonists. Arzneitmittelforschung 1963; 13: 1081–4

    CAS  Google Scholar 

  107. Felisati D. Teratogenic action of thalidomide. Lancet 1964; I: 724–5

    Article  Google Scholar 

  108. Evered DF, Randall HG. Thalidomide and the B vitamins [editorial]. Br Med J 1963; 5330: 610

    Article  Google Scholar 

  109. Rauen HM. Are thalidomide and its biological metabolites antagonists of glutamic acid. Arzneitmittelforschung 1964; 14: 111–5

    CAS  Google Scholar 

  110. McColl JD, Globus M, Robinson S. An attempted reversal of thalidomide embryopathy in the rat by glutamine. Can J Physiol Pharmacol 1965; 43: 69–73

    Article  PubMed  CAS  Google Scholar 

  111. Furberg S. Structural relationship between thalidomide and nucleosides. Acta Chem Scand 1965; 19: 1266–7

    Article  PubMed  CAS  Google Scholar 

  112. Papst W. Thalidomide and congenital abnormalities of the eye. Ber Deutsch Opth Ges 1964; 65: 209–15

    CAS  Google Scholar 

  113. Drugs and poisons in relation to the developing nervous system. Conference on drugs and poisons as etiological agents in mental retardation. Bethesda (MD): U.S. National Institute of Neurological Diseases and Blindness, 1967

    Google Scholar 

  114. Micks RH. The essentials of materia medica, pharmacology and therapeutics. London: J & A Churchill Ltd, 1965

    Google Scholar 

  115. Cant JS. Minor ocular abnormalities associated with thalidomide [letter]. Lancet 1966; I: 1134

    Article  Google Scholar 

  116. Hirsch M. Chromosomal studies on so-called thalidomide embryopathy. Med Klin 1963; 58: 397–400

    PubMed  CAS  Google Scholar 

  117. Bohm R, Nitsch K. Another chance for thalidomide [editorial]? Lancet 1966; I: 92

    Article  Google Scholar 

  118. Jensen MK. Chromosome aberrations in human cells induced by thalidomide in vitro: preliminary report. Acta Med Scand 1965; 117: 783–4

    Google Scholar 

  119. Ashby J. Thalidomide is not a mutagen [letter]. Nature 1997; 389: 118

    Article  PubMed  CAS  Google Scholar 

  120. Smithells D. Does thalidomide cause second generation birth defects? Drug Saf 1998; 19: 339–41

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Eduardo Bruera.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peuckmann, V., Fisch, M. & Bruera, E. Potential Novel Uses of Thalidomide. Drugs 60, 273–292 (2000). https://doi.org/10.2165/00003495-200060020-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200060020-00003

Keywords

Navigation