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Therapeutic Reviews| Volume 41, ISSUE 1, P140-145, January 01, 2011

Thalidomide

Open AccessPublished:October 22, 2010DOI:https://doi.org/10.1016/j.jpainsymman.2010.10.001
Thalidomide
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      Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. The content is also available on www.palliativedrugs.com and will feature in future editions of the Hospice and Palliative Care Formulary USA and its British and Canadian counterparts. The series editors welcome feedback on the articles ( [email protected] ).

      Abbreviations/Key

      †
      Off-label indication
      GI
      Gastrointestinal
      GVHD
      Graft vs. host disease
      HIV
      Human immunodeficiency virus
      PG
      Prostaglandin
      VTE
      Venous thrombo-embolism
      Class: Biologic response modifier.
      Indications: Multiple myeloma (with concurrent dexamethasone), cutaneous manifestations of lepromatous leprosy (erythema nodosum leprosum), †graft versus host disease (GVHD), †recurrent aphthous stomatitis in HIV infection and connective tissue disease (Behcet’s syndrome), †paraneoplastic sweating, †paraneoplastic and uremic pruritus, †cachexia in HIV and cancer, †intractable GI bleeding, †intractable irinotecan-induced diarrhea, †discoid lupus erythematosus, †rheumatoid arthritis, †prevention of graft rejection.
      • Calabrese L.
      • Fleischer A.
      Thalidomide: current and potential clinical applications.
      Am J Med. 2000; 108: 487-495
      , 
      • Chen M.
      • Doherty S.D.
      • Hsu S.
      Innovative uses of thalidomide.
      Dermatol Clin. 2010; 28: 577-586
      Contraindications: Because it causes severe congenital abnormalities (absent or shortened limbs), thalidomide is contraindicated in pregnant women and in women with childbearing potential unless strict contraception is implemented (see Dose and Use).
      • Celgene
      Prescribing information for Thalomid® thalidomide (THALPI.013 02/10 CG).
      http://www.thalomid.com/pdf/Thalomid%20PI%2072991-10.pdf
      Treatment should not be initiated with an absolute neutrophil count of <750/mm3.

      Pharmacology

      Thalidomide is an immunomodulator with anticytokine, anti-integrin, and anti-angiogenic properties.
      • Jacobson J.
      Thalidomide: a remarkable comeback.
      Expert Opin Pharmacother. 2000; 1: 849-863
      , 
      • De Sanctis J.B.
      • Mijares M.
      • Suárez A.
      • et al.
      Pharmacological properties of thalidomide and its analogues.
      Recent Pat Inflamm Allergy Drug Discov. 2010; 4: 144-148
      It was withdrawn from use as a non-barbiturate hypnotic with antiemetic properties in the early 1960s after it became apparent that it was teratogenic.
      • Marriott J.B.
      • Muller G.
      • Dalgleish A.G.
      Thalidomide as an emerging immunotherapeutic agent.
      Immunol Today. 1999; 20: 538-540
      Subsequently, it has been found to have immunomodulatory properties with potential for the treatment of various conditions.
      • Peuckmann V.
      • Fisch M.
      • Bruera E.
      Potential novel uses of thalidomide: focus on palliative care.
      Drugs. 2000; 60: 273-292
      However, its use is closely monitored and it is prohibitively expensive (see Supply).
      Thalidomide inhibits the synthesis of the pro-inflammatory cytokine tumor necrosis factor α (TNF-α) by monocytes,
      • Sampaio E.P.
      • Sarno E.N.
      • Galilly R.
      • Cohn Z.A.
      • Kaplan G.
      Thalidomide selectively inhibits tumour necrosis factor alpha production by stimulated human monocytes.
      J Exp Med. 1991; 173: 699-703
      and stimulates interleukin-2 and interferon-γ production (thereby stimulating human T lymphocytes).
      • Corral L.G.
      • Kaplan G.
      Immunomodulation by thalidomide and thalidomide analogues.
      Ann Rheum Dis. 1999; 58: I107-I113
      It also inhibits chemotaxis of neutrophils and monocytes. Thalidomide also has antiproliferative and pro-apoptotic activity in tumor cells.
      • Hideshima T.
      • Chauhan D.
      • Shima Y.
      • et al.
      Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy.
      Blood. 2000; 96: 2943-2950
      Thalidomide antagonizes PGE2, PGF2, histamine, serotonin, and acetylcholine.
      • Radomsky C.
      • Levine N.
      Thalidomide.
      Dermatol Clin. 2001; 19: 87-103
      It also affects several other mechanisms associated with inflammation and immunomodulation.
      • Bousvaros A.
      • Mueller B.
      Thalidomide in gastrointestinal disorders.
      Drugs. 2001; 61: 777-787
      These properties probably account for the prevention of irinotecan-induced diarrhea,
      • Govindarajan R.
      • Heaton K.M.
      • Broadwater R.
      • et al.
      Effect of thalidomide on gastrointestinal toxic effects of irinotecan.
      Lancet. 2000; 356: 566-567
      and for the amelioration of paraneoplastic sweating
      • Deaner P.
      The use of thalidomide in the management of severe sweating in patients with advanced malignancy: trial report.
      Palliat Med. 2000; 14: 429-431
      and paraneoplastic pruritus.

      Smith JC, Astley A, Johnstone S. Use of thalidomide in the treatment of intractable itch. Poster abstract 21. Palliative Care Congress, Sheffield, UK, 2002.

      Thalidomide also inhibits angiogenesis, a property that is the basis for investigational studies in oncology.
      • Eisen T.
      Thalidomide in solid tumors: the London experience.
      Oncology (Williston Park). 2000; 14: 17-20
      , 
      • Eleutherakis-Papaiakovou V.
      • Bamias A.
      • Dimopoulos M.A.
      Thalidomide in cancer medicine.
      Ann Oncol. 2004; 15: 1151-1160
      Thalidomide suppresses vascular endothelial growth factor (VEGF), a potent angiogenic factor secreted by cancer cells in response to hypoxia. This property also provides the rationale underlying the use of thalidomide in refractory GI bleeding.
      • Bauditz J.
      • Schachschal G.
      • Wedel S.
      • Lochs H.
      Thalidomide for treatment of severe intestinal bleeding.
      Gut. 2004; 53: 609-612
      , 
      • Craanen M.E.
      • van Triest B.
      • Verheijen R.H.
      • Mulder C.J.
      Thalidomide in refractory haemorrhagic radiation induced proctitis.
      Gut. 2006; 55: 1371-1372
      , 
      • Karajeh M.A.
      • Hurlstone D.P.
      • Stephenson T.J.
      • Ray-Chaudhuri D.
      • Gleeson D.C.
      Refractory bleeding from portal hypertensive gastropathy: a further novel role for thalidomide therapy?.
      Eur J Gastroenterol Hepatol. 2006; 18: 545-548
      , 
      • Lambert K.
      • Ward J.
      The use of thalidomide in the management of bleeding from a gastric cancer.
      Palliat Med. 2009; 23: 473-475
      Analogues of thalidomide with similar anti-angiogenic, immunomodulatory and anti-inflammatory properties have been developed.
      • Li S.
      • Gill N.
      • Lentzsch S.
      Recent advances of IMiDs in cancer therapy.
      Curr Opin Oncol. 2010 Aug 4; ([Epub ahead of print])
      For example, lenalidomide is approved in the USA and Europe for certain myelodysplastic syndromes that cause transfusion-dependent anemia
      • List A.
      • Kurtin S.
      • Roe D.J.
      • et al.
      Efficacy of lenalidomide in myelodysplastic syndromes.
      N Engl J Med. 2005; 352: 549-557
      , 
      • Giagounidis A.A.
      • Germing U.
      • Aul C.
      Biological and prognostic significance of chromosome 5q deletions in myeloid malignancies.
      Clin Cancer Res. 2006; 12: 5-10
      , 
      • Naing A.
      • Sokol L.
      • List A.F.
      Developmental therapeutics for myelodysplastic syndromes.
      J Natl Compr Canc Netw. 2006; 4: 78-82
      and, with concurrent dexamethasone, as a second-line treatment in multiple myeloma.
      • Richardson P.
      • Mitsiades C.
      • Laubach J.
      • et al.
      Lenalidomide in multiple myeloma: an evidence-based review of its role in therapy.
      Core Evid. 2010; 4: 215-245
      However, lenalidomide is also presumed to carry serious teratogenic risk, is restricted in its availability, is expensive, and in multiple myeloma is associated with an increased risk of VTE. Further, there is a dearth of experience with lenalidomide in symptom management and palliative care, and no obvious advantage over thalidomide.
      The metabolism of thalidomide is by non-enzymatic hydrolysis in plasma. Hepatic metabolism is minor.
      • Celgene
      Prescribing information for Thalomid® thalidomide (THALPI.013 02/10 CG).
      http://www.thalomid.com/pdf/Thalomid%20PI%2072991-10.pdf
      Studies in patients with hepatic and renal impairment have not been performed.
      Bioavailability: 67–93% PO in animals, no data in humans.
      Onset of action: varies from 2 days for lepromatous leprosy and paraneoplastic sweating to 1–2 months for GVHD and 2–3 months for rheumatoid arthritis.
      Time to peak plasma concentration: 2–6 h, delayed by food.
      Plasma half-life: 6 h (200 mg/24 h)–18 h (800 mg/24 h).
      • Bousvaros A.
      • Mueller B.
      Thalidomide in gastrointestinal disorders.
      Drugs. 2001; 61: 777-787
      Duration of action: 24 h.

      Cautions

      For full list, see manufacturer’s Prescribing Information.
      Treat as a “cytotoxic” when handling. Thalidomide potentiates the sedative properties of barbiturates and alcohol, and increases the likelihood of extrapyramidal effects with chlorpromazine and reserpine.
      • Radomsky C.
      • Levine N.
      Thalidomide.
      Dermatol Clin. 2001; 19: 87-103
      Thalidomide should be used cautiously with other drugs that cause drowsiness, neuropathy or reduce the effectiveness of oral contraception (e.g., HIV protease inhibitors, rifampin, rifabutin, phenytoin and carbamazepine).
      • Radomsky C.
      • Levine N.
      Thalidomide.
      Dermatol Clin. 2001; 19: 87-103
      , 
      • Thomas D.
      • Kantarjian H.
      Current role of thalidomide in cancer treatment.
      Curr Opin Oncol. 2000; 12: 564-573

      Undesirable Effects

      For full list, see manufacturer’s Prescribing Information.
      Low-grade peripheral neuropathy occurs in >80% of patients receiving thalidomide, and severe neuropathy in 3–5%, generally after treatment lasting >6 months.
      • Dimopoulos M.A.
      • Eleutherakis-Papaiakovou V.
      Adverse effects of thalidomide administration in patients with neoplastic diseases.
      Am J Med. 2004; 117: 508-515
      , 
      • Mileshkin L.
      • Stark R.
      • Day B.
      • et al.
      Development of neuropathy in patients with myeloma treated with thalidomide: patterns of occurrence and the role of electrophysiologic monitoring.
      J Clin Oncol. 2006; 24: 4507-4514
      The incidence is higher in elderly patients, women, and in patients with pre-existing neuropathy or who are treated with neurotoxic chemotherapy, e.g., vincristine, cisplatin, paclitaxel.
      • Mileshkin L.
      • Stark R.
      • Day B.
      • et al.
      Development of neuropathy in patients with myeloma treated with thalidomide: patterns of occurrence and the role of electrophysiologic monitoring.
      J Clin Oncol. 2006; 24: 4507-4514
      Generally, the peripheral neuropathy presents as distal paresthesia or dysesthesia with or without sensory loss. Physical examination may be normal or show mildly decreased sensation in the distal limbs. Strength is usually preserved, but reflexes, particularly ankle jerks, may be depressed or absent. These symptoms, which are progressive, typically begin in the distal lower limbs and extend proximally and into the upper limbs.
      • Wulff C.H.
      • Høyer H.
      • Asboe-Hansen G.
      • Brodthagen H.
      Development of polyneuropathy during thalidomide therapy.
      Br J Dermatol. 1985; 112: 475-480
      Although some studies have found a relationship between the cumulative dose and the occurrence of neuropathy,
      • Fullerton P.
      • O’Sullivan D.
      Thalidomide neuropathy: a clinical, electrophysiological, and histological follow up study.
      J Neurol Neurosurg Psychiatry. 1968; 31: 543-551
      others have not.
      • Chapon F.
      • Lechevalier B.
      • da Silva D.C.
      • et al.
      [Neuropathies caused by thalidomide].
      Rev Neurol (Paris). 1985; 141 ([French]): 719-728
      Nerve conduction studies typically show results consistent with a sensory axonal neuropathy. If a patient develops symptomatic neuropathy, thalidomide should be stopped to decrease the likelihood of chronic painful neuropathy.
      • Gardner-Medwin J.M.
      • Smith N.J.
      • Powell R.J.
      Clinical experience with thalidomide in the management of severe oral and genital ulceration in conditions such as Behcet’s disease: use of neurophysiological studies to detect thalidomide neuropathy.
      Ann Rheum Dis. 1994; 128: 443-450
      , 
      • Ochonisky S.
      • Verroust J.
      • Bastuji-Garin S.
      • Gherardi R.
      • Revuz J.
      Thalidomide neuropathy incidence and clinico-electrophysiologic findings in 42 patients.
      Arch Dermatol. 1994; 130: 66-69
      Some 80% of patients experience a mild decrease in bowel motility; this may reflect autonomic dysfunction, and can exacerbate constipation.
      • Grover J.K.
      • Uppal G.
      • Raina V.
      The adverse effects of thalidomide in relapsed and refractory patients of multiple myeloma.
      Ann Oncol. 2002; : 636-1640
      Somnolence or sedation may also occur and is the reason for taking the daily thalidomide dose at bedtime.
      • Palumbo A.
      • Rajkumar S.V.
      • Dimopoulos M.A.
      • et al.
      Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma.
      Leukemia. 2008; 22: 414-423
      Thalidomide (and lenalidomide) increase the risk of VTE in patients with multiple myeloma, particularly when used in combination with high-dose dexamethasone and/or anthracycline-based chemotherapy, and thromboprophylaxis is recommended.
      • Palumbo A.
      • Rajkumar S.V.
      • Dimopoulos M.A.
      • et al.
      Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma.
      Leukemia. 2008; 22: 414-423
      , 
      • Uaprasert N.
      • Voorhees P.M.
      • Mackman N.
      • Key N.S.
      Venous thromboembolism in multiple myeloma: current perspectives in pathogenesis.
      Eur J Cancer. 2010; 46: 1790-1799
      There is insufficient evidence to warrant routine thromboprophylaxis when thalidomide is used in symptom control, but close monitoring would be prudent in patients at high risk of VTE.
      Thalidomide is associated with arrhythmia, hypotension, and edema. Sinus bradycardia, generally mild, has been reported in ≤25% of patients.
      • Kaur A.
      • Yu S.S.
      • Lee A.J.
      • Chiao T.B.
      Thalidomide-induced sinus bradycardia.
      Ann Pharmacother. 2003; 37: 1040-1043
      Severe sinus bradycardia occurs in only 1–3% of patients.
      • Eisen T.
      Thalidomide in solid tumors: the London experience.
      Oncology (Williston Park). 2000; 14: 17-20
      Mild peripheral edema has been reported in 15%.
      • Sampaio E.P.
      • Sarno E.N.
      • Galilly R.
      • Cohn Z.A.
      • Kaplan G.
      Thalidomide selectively inhibits tumour necrosis factor alpha production by stimulated human monocytes.
      J Exp Med. 1991; 173: 699-703
      Orthostatic hypotension and dizziness also have been reported with thalidomide.
      • Clark T.E.
      • Edom N.
      • Larson J.
      • Lindsey L.J.
      Thalidomid (Thalidomide) capsules: A review of the first 18 months of spontaneous postmarketing adverse event surveillance, including off-label prescribing.
      Drug Saf. 2001; 24: 87-117
      A dose-dependent decrease in supine systolic and diastolic pressures is seen up to 2 h after dosing.
      • Noormohamed F.H.
      • Youle M.S.
      • Higgs C.J.
      • et al.
      Pharmacokinetics and hemodynamic effects of single oral doses of thalidomide in asymptomatic human immunodeficiency virus-infected subjects.
      AIDS Res Hum Retroviruses. 1999; 15: 1047-1052
      However, symptom control doses should not affect blood pressure.
      A pruritic and maculopapular rash may occur 10–14 days after starting treatment, starting on the trunk and extending to the back and proximal limbs. This is generally mild and resolves with the use of an emollient and dose reduction.
      • Ng S.S.
      • Brown M.
      • Figg W.D.
      Thalidomide, an antiangiogenic agent with clinical activity in cancer.
      Biomed Pharmacother. 2002; 56: 194-199
      Severe skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, may also occur.
      • Rajkumar S.V.
      • Gertz M.A.
      • Witzig T.E.
      Life-threatening toxic epidermal necrolysis with thalidomide therapy for myeloma.
      N Engl J Med. 2000; 343: 972-973
      Skin complications seem more likely when thalidomide is combined with dexamethasone.
      Tumor flare (a temporary increase in size of a cancerous lesion) may occur. When thalidomide is used to treat chronic lymphocytic leukemia, some patients have experienced increased lymphadenopathy, enlargement of the spleen, and an increased lymphocyte count.
      • Chanan-Khan A.
      • Miller K.C.
      • Takeshita K.
      • et al.
      Results of a phase 1 clinical trial of thalidomide in combination with fludarabine as initial therapy for patients with treatment-requiring chronic lymphocytic leukemia (CLL).
      Blood. 2005; 106: 3348-3352
      Other undesirable effects include seizures,
      • Clark T.E.
      • Edom N.
      • Larson J.
      • Lindsey L.J.
      Thalidomid (Thalidomide) capsules: A review of the first 18 months of spontaneous postmarketing adverse event surveillance, including off-label prescribing.
      Drug Saf. 2001; 24: 87-117
      altered temperature sensitivity, irregular menstrual cycles, and hypothyroidism. Thalidomide can increase HIV viral load.
      • Marriott J.B.
      • Cookson S.
      • Carlin E.
      • et al.
      A double-blind placebo-controlled phase II trial of thalidomide in asymptomatic HIV-positive patients: clinical tolerance and effect on activation markers and cytokines.
      AIDS Res Hum Retroviruses. 1997; 13: 1625-1631
      Myelosuppression is rare.

      Dose and Use

      Thalidomide is prohibitively expensive and cost alone will severely limit its use. In palliative care, thalidomide should never be considered as a first-line treatment. Its use should be considered only when more conventional treatments have failed and a full review of the potential benefits and harms has been undertaken with specialist colleagues.
      There are several potential uses for thalidomide in palliative care (Table 1).
      • Davis M.
      • Dickerson E.
      Thalidomide: dual benefits in palliative medicine and oncology.
      Am J Hosp Palliat Care. 2001; 18: 347-351
      Female patients prescribed thalidomide must be counseled about the need for contraception, and male patients must use a condom. Written consent should be obtained.
      • Powell R.
      • Gardner-Medwin J.
      Guideline for the clinical use and dispensing of thalidomide.
      Postgrad Med J. 1994; 70: 901-904
      Contraception should be used for ≥4 weeks before starting, during, and for 4 weeks after stopping treatment. Regular pregnancy testing is advised throughout treatment. Because thalidomide is present in the semen of men treated with the drug, even after vasectomy a latex condom must be used during sexual intercourse with women of childbearing potential.
      • Teo S.K.
      • Harden J.L.
      • Burke A.B.
      • et al.
      Thalidomide is distributed into human semen after oral dosing.
      Drug Metab Dispos. 2001; 29: 1355-1357
      Table 1Potential Uses of Thalidomide in Palliative Care
      Thalidomide is not the first-line treatment for any of these indications.
      IndicationDoseReference
      Aphthous ulcers in HIV+ disease100–200 mg at bedtime for 10 days
      • Jacobson J.M.
      • Greenspan J.S.
      • Spritzler J.
      • et al.
      Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection.
      N Engl J Med. 1997; 336: 1487-1493
      Paraneoplastic sweating100–200 mg at bedtime
      • Deaner P.
      Thalidomide for distressing night sweats in advanced malignant disease.
      Palliat Med. 1998; 12: 208-209
      , 
      • Calder K.
      • Bruera E.
      Thalidomide for night sweats in patients with advanced cancer.
      Palliat Med. 2000; 14: 77-78
      Paraneoplastic and uremic pruritus100–200 mg at bedtime

      Smith JC, Astley A, Johnstone S. Use of thalidomide in the treatment of intractable itch. Poster abstract 21. Palliative Care Congress, Sheffield, UK, 2002.

      , 
      • Goncalves F.
      Thalidomide for the control of severe paraneoplastic pruritus associated with Hodgkin’s disease.
      Am J Hosp Palliat Care. 2010 Mar 15; ([Epub ahead of print])
      , 
      • Silva S.R.
      • Viana P.C.
      • Lugon N.V.
      • et al.
      Thalidomide for the treatment of uremic pruritus: a crossover randomized double-blind trial.
      Nephron. 1994; 67: 270-273
      Cachexia in HIV+ disease and cancer100–200 mg at bedtime
      • Boasberg P.
      • O’Day S.
      • Weisberg M.
      • et al.
      Thalidomide induced cessation of weight loss and improved sleep in advanced cancer patients with cachexia.
      Proc Am Soc Clin Oncol. 2000; 19 (Abstract 2396): 609a
      , 
      • Mantovani G.
      • Macciò A.
      • Massa E.
      • Madeddu C.
      Managing cancer-related anorexia/cachexia.
      Drugs. 2001; 61: 499-514
      , 
      • Gordon J.N.
      • Trebble T.M.
      • Ellis R.D.
      • et al.
      Thalidomide in the treatment of cancer cachexia: a randomised placebo controlled trial.
      Gut. 2005; 54: 540-545
      GI bleeding associated with angiodysplasia/radiation proctitis100–300 mg at bedtime
      • Lambert K.
      • Ward J.
      The use of thalidomide in the management of bleeding from a gastric cancer.
      Palliat Med. 2009; 23: 473-475
      Intractable irinotecan-induced diarrhea400 mg at bedtime
      • Govindarajan R.
      • Heaton K.M.
      • Broadwater R.
      • et al.
      Effect of thalidomide on gastrointestinal toxic effects of irinotecan.
      Lancet. 2000; 356: 566-567
      , 
      • Govindarajan R.
      Irinotecan and thalidomide in metastatic colorectal cancer.
      Oncology (Williston Park). 2000; 14: 29-32
      a Thalidomide is not the first-line treatment for any of these indications.

      Supply

      Thalidomide is available in some countries through a strictly monitored program: in the USA, the System for Thalidomide Education and Prescribing Safety (STEPS) and, in Canada, the Canadian Thalomid Access Program (CANTAP). Clinicians wishing to use thalidomide must be registered with the program.
      Lenalidomide is available through a similar distribution program, RevAssist in the USA (www.REVLIMID.com) and RevAid in Canada (www.RevAid.ca).

      Thalidomide

      Thalomid® (Celgene)
      Capsules 50 mg, 100 mg, 150 mg, 200 mg, 28 days @ 200 mg at bedtime=$7,056.

      Lenalidomide

      Revlimid® (Celgene)
      Capsules 5 mg, 10 mg, 15 mg, 25 mg, 28 days @ 10 mg once daily=$10,800.

      References

        • Calabrese L.
        • Fleischer A.
        Thalidomide: current and potential clinical applications.
        Am J Med. 2000; 108: 487-495
        View in Article
        • Chen M.
        • Doherty S.D.
        • Hsu S.
        Innovative uses of thalidomide.
        Dermatol Clin. 2010; 28: 577-586
        View in Article
        • Celgene
        Prescribing information for Thalomid® thalidomide (THALPI.013 02/10 CG).
        (Available from)
        http://www.thalomid.com/pdf/Thalomid%20PI%2072991-10.pdf
        (Accessed October 1, 2010)
        View in Article
        • Jacobson J.
        Thalidomide: a remarkable comeback.
        Expert Opin Pharmacother. 2000; 1: 849-863
        View in Article
        • De Sanctis J.B.
        • Mijares M.
        • Suárez A.
        • et al.
        Pharmacological properties of thalidomide and its analogues.
        Recent Pat Inflamm Allergy Drug Discov. 2010; 4: 144-148
        View in Article
        • Marriott J.B.
        • Muller G.
        • Dalgleish A.G.
        Thalidomide as an emerging immunotherapeutic agent.
        Immunol Today. 1999; 20: 538-540
        View in Article
        • Peuckmann V.
        • Fisch M.
        • Bruera E.
        Potential novel uses of thalidomide: focus on palliative care.
        Drugs. 2000; 60: 273-292
        View in Article
        • Sampaio E.P.
        • Sarno E.N.
        • Galilly R.
        • Cohn Z.A.
        • Kaplan G.
        Thalidomide selectively inhibits tumour necrosis factor alpha production by stimulated human monocytes.
        J Exp Med. 1991; 173: 699-703
        View in Article
        • Corral L.G.
        • Kaplan G.
        Immunomodulation by thalidomide and thalidomide analogues.
        Ann Rheum Dis. 1999; 58: I107-I113
        View in Article
        • Hideshima T.
        • Chauhan D.
        • Shima Y.
        • et al.
        Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy.
        Blood. 2000; 96: 2943-2950
        View in Article
        • Radomsky C.
        • Levine N.
        Thalidomide.
        Dermatol Clin. 2001; 19: 87-103
        View in Article
        • Bousvaros A.
        • Mueller B.
        Thalidomide in gastrointestinal disorders.
        Drugs. 2001; 61: 777-787
        View in Article
        • Govindarajan R.
        • Heaton K.M.
        • Broadwater R.
        • et al.
        Effect of thalidomide on gastrointestinal toxic effects of irinotecan.
        Lancet. 2000; 356: 566-567
        View in Article
        • Deaner P.
        The use of thalidomide in the management of severe sweating in patients with advanced malignancy: trial report.
        Palliat Med. 2000; 14: 429-431
        View in Article

      15. Smith JC, Astley A, Johnstone S. Use of thalidomide in the treatment of intractable itch. Poster abstract 21. Palliative Care Congress, Sheffield, UK, 2002.

        View in Article
        • Eisen T.
        Thalidomide in solid tumors: the London experience.
        Oncology (Williston Park). 2000; 14: 17-20
        View in Article
        • Eleutherakis-Papaiakovou V.
        • Bamias A.
        • Dimopoulos M.A.
        Thalidomide in cancer medicine.
        Ann Oncol. 2004; 15: 1151-1160
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      Article Info

      Publication History

      Published online: October 22, 2010
      Accepted: September 27, 2010
      AHFS 92:2000

      Footnotes

      Series Co-Editors: Andrew Wilcock, DM, FRCP, and Robert Twycross, DM, FRCP

      Identification

      DOI: https://doi.org/10.1016/j.jpainsymman.2010.10.001

      Copyright

      © 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc.

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