Editing Thalidomide (section)

==History==
In 1952, thalidomide was synthesised by [[Novartis#Ciba-Geigy|Chemical Industry Basel]], but was found "to have no effect on animals" and was discarded on that basis.<ref name="themee">{{Cite web |last=Royal Pharmaceutical Society |date=2011 |title=The evolution of pharmacy, Theme E, Level 3 Thalidomide and its aftermath |url=https://www.rpharms.com/museum-pdfs/e3a-thalidomide-and-its-aftermath-2011.pdf |archive-url=https://web.archive.org/web/20141009110927/https://www.rpharms.com/museum-pdfs/e3a-thalidomide-and-its-aftermath-2011.pdf |archive-date=9 October 2014}}</ref>  In 1957, it was acquired by [[Grünenthal|Chemie Grünenthal]] in Germany.<ref name=themee/> The German company had been established as a soap maker after World War II ended, to address the urgent market need for antibiotics.<ref>{{Cite book |title=Introducing HR Analytics with Machine Learning: Empowering Practitioners, Psychologists, and Organizations |vauthors=Rosett CM, Hagerty A |date=2021 |publisher=Springer International Publishing |isbn=978-3-030-67626-1 |veditors=Rosett CM, Hagerty A |location=Cham |pages=171–189 |language=en |chapter=What History Can Teach us About Using Machine Learning Well |doi=10.1007/978-3-030-67626-1_10 |s2cid=236710887}}</ref> [[Heinrich Mückter]]<ref name="ktnyt">{{Cite news |date=23 March 2020 |title=The Unseen Survivors of Thalidomide Want to Be Heard |url=https://www.nytimes.com/2020/03/23/health/thalidomide-survivors-usa.html |url-status=live |archive-url=https://web.archive.org/web/20200323154020/https://www.nytimes.com/2020/03/23/health/thalidomide-survivors-usa.html |archive-date=23 March 2020 |access-date=23 March 2020 |work=The New York Times |language=en-US |issn=0362-4331 |vauthors=Thomas K}}</ref> was appointed to head the discovery program based on his experience working with the German army's antiviral research. While preparing [[reagents]] for the work, Mueckter's assistant Wilhelm Kunz isolated a by-product that was recognized by pharmacologist Herbert Keller as an analog of [[glutethimide]], a [[sedative]]. The medicinal chemistry work turned to improving the lead compound into a suitable drug: the result was thalidomide. The toxicity was examined in several animals, and the drug was introduced in 1956 as a sedative, but it was never tested on pregnant women.<ref>{{Cite book |url=https://archive.org/details/drugdiscoveryhis00snea |title=Drug discovery: a history |vauthors=Sneader W |date=2005 |publisher=Wiley |isbn=978-0-471-89979-2 |edition=Rev. and updated |location=Chichester |page=[https://archive.org/details/drugdiscoveryhis00snea/page/n380 367] |url-access=limited}}</ref>

Researchers at Chemie Grünenthal found that thalidomide was a particularly effective [[antiemetic]] that had an inhibitory effect on [[morning sickness]].<ref name="pmid15172781">{{Cite journal |vauthors=Franks ME, Macpherson GR, Figg WD |date=May 2004 |title=Thalidomide |url=https://zenodo.org/record/1259793 |url-status=live |journal=Lancet |volume=363 |issue=9423 |pages=1802–11 |doi=10.1016/S0140-6736(04)16308-3 |pmid=15172781 |s2cid=208789946 |archive-url=https://web.archive.org/web/20190821212125/https://zenodo.org/record/1259793 |archive-date=21 August 2019 |access-date=30 June 2019}}</ref> On 1 October 1957, the company launched thalidomide and began marketing it under the trade name Contergan.<ref>{{Cite web |title=Grünenthal: Where we come from |url=https://www.grunenthal.com/about-us/history |archive-url=https://web.archive.org/web/20180702093114/https://www.grunenthal.com/about-us/history |archive-date=2 July 2018 |access-date=2 July 2018}} See also {{cite web | url = http://www.contergan.grunenthal.info/thalidomid/Home_/351300028.jsp;jsessionid=D8966B9045A2EDE78D5AC41F85C93424.drp1?naviLocale=en_EN | title = Developments regarding thalidomide | archive-url = https://web.archive.org/web/20180702064501/http://www.contergan.grunenthal.info/thalidomid/Home_/351300028.jsp;jsessionid=D8966B9045A2EDE78D5AC41F85C93424.drp1?naviLocale=en_EN | archive-date=2 July 2018 }}</ref><ref name="Bombay">{{Cite journal |vauthors=Moghe VV, Kulkarni U, Parmar UI |year=2008 |title=Thalidomide |url=http://www.bhj.org.in/journal/2008_5003_july/download/page-472-476.pdf |url-status=live |journal=Bombay Hospital Journal |location=Bombay |publisher=Bombay Hospital |volume=50 |issue=3 |pages=472–6 |archive-url=https://web.archive.org/web/20160820114658/http://www.bhj.org.in/journal/2008_5003_july/download/page-472-476.pdf |archive-date=20 August 2016 |access-date=8 August 2016}}</ref> It was proclaimed a "wonder drug" for [[insomnia]], coughs, colds and headaches.<ref>Campbell, Denis. "'Wonder drug' left babies with deformed limbs." ''The Guardian''. 29 July 2009.</ref>

During that period, the use of medications during pregnancy was not strictly controlled, and drugs were not thoroughly tested for potential harm to the [[fetus]].<ref name=pmid15172781/> Thousands of pregnant women took the drug to relieve their symptoms. At the time of the drug's development, scientists did not believe any drug taken by a pregnant woman could pass across the [[placental barrier]] and harm the developing fetus.<ref name="Chem1994">{{Cite book |title=The Chemical Industry |vauthors=Heaton CA |publisher=Springer |year=1994 |isbn=978-0-7514-0018-2}}</ref> There soon appeared reports of abnormalities in children being born to mothers using thalidomide. In late 1959, it was noticed that [[peripheral neuritis]] developed in patients who took the drug over a period of time, and it was only after this point that thalidomide ceased to be provided over the counter.<ref>{{Cite journal |vauthors=Kelsey FO |year=1967 |title=Events after thalidomide |journal=Journal of Dental Research |volume=46 |issue=6 |pages=1201–5 |doi=10.1177/00220345670460061201 |pmid=5235007 |s2cid=11175347}}</ref>

While initially considered safe, the drug was responsible for [[teratogenic]] deformities in children born after their mothers used it during pregnancies, prior to the third trimester. In November 1961, thalidomide was taken off the market due to massive pressure from the press and public.<ref>{{Cite journal |vauthors=Vargesson N, Stephens T |date=December 2021 |title=Thalidomide: history, withdrawal, renaissance, and safety concerns |journal=Expert Opinion on Drug Safety |volume=20 |issue=12 |pages=1455–1457 |doi=10.1080/14740338.2021.1991307 |pmid=34623196 |s2cid=238476677 |hdl-access=free |hdl=2164/19455}}</ref> Experts estimate that thalidomide led to the death of approximately 2,000 children and serious birth defects in more than 10,000 children, with over half of them in West Germany.<ref name="Thalidomide-induced teratogenesis">{{Cite journal |vauthors=Vargesson N |date=June 2015 |title=Thalidomide-induced teratogenesis: history and mechanisms |journal=Birth Defects Research. Part C, Embryo Today |volume=105 |issue=2 |pages=140–156 |doi=10.1002/bdrc.21096 |pmc=4737249 |pmid=26043938}}</ref> The regulatory authorities in [[East Germany]] never approved thalidomide.<ref name="oncozine.com">{{Cite web |date=December 2013 |title=Reversal of Fortune: How a Vilified Drug Became a Life-saving Agent in the "War" Against Cancer |url=https://oncozine.com/reversal-of-fortune-how-a-vilified-drug-became-a-life-saving-agent-in-the-war-against-cancer/ |url-status=live |archive-url=https://web.archive.org/web/20180211072029/https://oncozine.com/reversal-of-fortune-how-a-vilified-drug-became-a-life-saving-agent-in-the-war-against-cancer/ |archive-date=11 February 2018 |access-date=10 February 2018 |website=Onco'Zine |vauthors=Hofland P}}</ref> One reason for the initially unobserved side effects of the drug and the subsequent approval in West Germany was that at that time drugs did not have to be tested for teratogenic effects. They were tested for toxicity on rodents only, as was usual at the time.<ref name="VFA">{{Cite web |date=6 July 2011 |title=VFA: teratogenic effects |url=http://www.vfa.de/de/arzneimittel-forschung/artikel-arzneimittel-forschung/teratogenitaet.html |archive-url=https://web.archive.org/web/20140104022807/http://www.vfa.de/de/arzneimittel-forschung/artikel-arzneimittel-forschung/teratogenitaet.html |archive-date=4 January 2014}}</ref>

In the UK, the British pharmaceutical company [[The Distillers Company]] (Biochemicals) Ltd, a subsidiary of Distillers Co. Ltd (now part of [[Diageo plc]]), marketed thalidomide throughout the UK, Australia, and New Zealand, under the brand name Distaval, as a remedy for [[morning sickness]]. Their advertisement claimed that "Distaval can be given with complete safety to pregnant women and nursing mothers without adverse effect on mother or child ... Outstandingly safe Distaval has been prescribed for nearly three years in this country."<ref name="oncozine.com" /> Globally, more pharmaceutical companies started to produce and market the drug under license from Chemie Grünenthal. Thalidomide was available in 46 countries under many different brand names.<ref>{{Cite book | vauthors = Ghosh TK, Jasti BR |url=https://books.google.com/books?id=RFwkEAAAQBAJ&dq=marketing+thalidomide+46+countries&pg=PA260 |title=Theory and Practice of Contemporary Pharmaceutics |date=2021-02-25 |publisher=CRC Press |isbn=978-1-134-44195-2 |language=en}}</ref>

In the US, representatives from Chemie Grünenthal approached [[Smith, Kline & French]] (SKF), now [[GlaxoSmithKline]], with a request to market and distribute the drug in North America. A memorandum, rediscovered in 2010 in the archives of the FDA, shows that in 1956–57, as part of its in-licensing approach, Smith, Kline and French conducted animal tests and ran a clinical trial of the drug in the US involving 875 people, including pregnant women.<ref>{{Cite web |title=Lawsuit Blames Thalidomide for More Birth Defects |url=https://www.scientificamerican.com/article/lawsuit-blames-thalidomide-for-more/ |url-status=live |archive-url=https://web.archive.org/web/20230204035126/https://www.scientificamerican.com/article/lawsuit-blames-thalidomide-for-more/ |archive-date=4 February 2023 |access-date=2023-02-04 |website=Scientific American |language=en}}</ref> In 1956, researchers involved in clinical trials at SKF noted that, even when used in very high doses, thalidomide could not induce sleep in mice.<ref>{{Cite book |url=https://books.google.com/books?id=XAxYur9IzCsC&dq=thalidomide+sleep+mice&pg=PA111 |title=Animal Research Takes Lives: Humans and Animals Both Suffer |date=1993 |publisher=NZ Anti-Vivisection Society Inc. |isbn=978-0-473-01846-7 |language=en}}</ref> When administered at doses 50 to 650 times larger than that claimed by Chemie Grünenthal to be "sleep-inducing", the researchers could still not achieve the hypnotic effect in animals that it had on humans.{{citation needed|date=October 2015}} After completion of the trial, and based on reasons kept hidden for decades, SKF declined to commercialize the drug. In 1958, Chemie Grünenthal reached an agreement with the William S. Merrell Company in Cincinnati, Ohio ([[Marion Merrell Dow#Richardson-Merrell|later Richardson-Merrell]], now part of [[Sanofi]]), to market and distribute thalidomide throughout the US.<ref name="oncozine.com" />

The US FDA refused to approve thalidomide for marketing and distribution. However, the drug was distributed in large quantities for testing purposes, after the American distributor and manufacturer [[Marion Merrell Dow#Richardson-Merrell|Richardson-Merrell]] had applied for its approval in September 1960.<ref>{{Cite book | vauthors = Hawthorne F |url=https://books.google.com/books?id=dfVGMxn9GwcC&dq=thalidomide+Richardson-Merrell+1960+september&pg=PT37 |title=Inside the FDA: The Business and Politics Behind the Drugs We Take and the Food We Eat |date=2010-12-13 |publisher=John Wiley & Sons |isbn=978-1-118-04006-5 |language=en}}</ref> The official in charge of the FDA review, [[Frances Oldham Kelsey]], did not rely on information from the company, which did not include any test results. Richardson-Merrell was called on to perform tests and report the results. The company demanded approval six times and was refused each time. The distribution for "testing" resulted in 17 children born in the US with thalidomide-induced malformations. Oldham Kelsey was awarded the [[President's Award for Distinguished Federal Civilian Service]] by President Kennedy in 1962 for not allowing thalidomide to be approved for sale in the US. She was also inducted into the [[National Women's Hall of Fame]] in 2000.<ref>{{Cite web |date=12 May 2009 |title=Report |url=https://www.fda.gov/fdac/features/2001/201_kelsey.html |archive-url=https://web.archive.org/web/20090512235601/https://www.fda.gov/fdac/features/2001/201_kelsey.html |archive-date=12 May 2009 |publisher=U.S. Food and Drug Administration}}</ref>

Canada's Food and Drug Directorate approved the sale of thalidomide by prescription in November 1960.<ref name="Peritz2014">{{Cite news |date=November 21, 2014 |title=The fight of their lives: After years of neglect, Canadian thalidomide survivors make a plea for help |url=https://www.theglobeandmail.com/news/national/the-aftermath-of-thalidomide/article21689771/ |url-status=live |archive-url=https://web.archive.org/web/20230205215237/https://www.theglobeandmail.com/news/national/the-aftermath-of-thalidomide/article21689771/ |archive-date=5 February 2023 |access-date=5 February 2023 |work=[[The Globe and Mail]] |vauthors=Peritz I}}</ref> There were many different forms sold: Kevadon, produced by the William S. Merrell Company seeking approval for its thalidomide product, was released on the market in April 1961, and the most common variant (Horner's Talimol) was put on the market on October 23 of the same year.<ref name="pmid14076167">{{Cite journal |vauthors=Webb JF |date=November 1963 |title=Canadian Thalidomide Experience |journal=Canadian Medical Association Journal |volume=89 |issue=19 |pages=987–92 |pmc=1921912 |pmid=14076167}}</ref> Two months after Talimol went on sale, pharmaceutical companies sent physicians letters warning about the risk of birth defects.<ref name=pmid14076167/> It was not until March 1962 that both drugs were banned from the Canadian market by the directorate, and soon afterward physicians were warned to destroy their supplies.<ref name=pmid14076167/>

===Leprosy treatment===
In 1964, Israeli physician [[Jacob Sheskin]] administered thalidomide to a patient critically ill with [[leprosy]]. The patient exhibited [[Erythema nodosum|erythema nodosum leprosum]] (ENL), a painful skin condition, one of the complications of leprosy. The treatment was attempted despite the ban on thalidomide's use, and the results were favourable: the patient slept for hours and was able to get out of bed without aid upon awakening. A clinical trial studying the use of thalidomide in leprosy soon followed.<ref name="Silverman">{{Cite journal |vauthors=Silverman WA |date=August 2002 |title=The schizophrenic career of a "monster drug" |journal=Pediatrics |volume=110 |issue=2 Pt 1 |pages=404–6 |doi=10.1542/peds.110.2.404 |pmid=12165600}}</ref>

Thalidomide has been used by Brazilian physicians as the drug of choice for the treatment of severe ENL since 1965, and by 1996, at least 33 cases of thalidomide embryopathy were recorded in people born in Brazil after 1965.<ref>{{Cite journal |vauthors=Castilla EE, Ashton-Prolla P, Barreda-Mejia E, Brunoni D, Cavalcanti DP, Correa-Neto J, Delgadillo JL, Dutra MG, Felix T, Giraldo A, Juarez N, Lopez-Camelo JS, Nazer J, Orioli IM, Paz JE, Pessoto MA, Pina-Neto JM, Quadrelli R, Rittler M, Rueda S, Saltos M, Sánchez O, Schüler L |date=December 1996 |title=Thalidomide, a current teratogen in South America |journal=Teratology |volume=54 |issue=6 |pages=273–7 |doi=10.1002/(SICI)1096-9926(199702)55:2<156::AID-TERA6>3.0.CO;2-1 |pmid=9098920 |doi-access=free}}</ref> Since 1994, the production, dispensing, and prescription of thalidomide have been strictly controlled, requiring women to use two forms of birth control and submit to regular pregnancy tests. Despite this, cases of thalidomide embryopathy continue,<ref>{{Cite journal |vauthors=Paumgartten FJ, Chahoud I |date=July 2006 |title=Thalidomide embryopathy cases in Brazil after 1965 |journal=Reproductive Toxicology |volume=22 |issue=1 |pages=1–2 |bibcode=2006RepTx..22....1P |doi=10.1016/j.reprotox.2005.11.007 |pmid=16427249}}</ref><ref>{{Cite web |date=January 2006 |title=Talidomida volta a assustar |trans-title=Thalidomide again scare |url=http://www.saude.df.gov.br/003/00301009.asp?ttCD_CHAVE=31041 |url-status=dead |archive-url=https://web.archive.org/web/20120313095445/http://www.saude.df.gov.br/003/00301009.asp?ttCD_CHAVE=31041 |archive-date=13 March 2012 |language=pt |vauthors=Braziliense C}}</ref> with at least 100 cases identified in Brazil between 2005 and 2010.<ref>{{Cite news |date=23 July 2013 |title=Brazil's new generation of Thalidomide babies |url=https://www.bbc.com/news/magazine-23418102 |url-status=live |archive-url=https://web.archive.org/web/20201110015129/https://www.bbc.com/news/magazine-23418102 |archive-date=10 November 2020 |access-date=21 June 2018 |work=BBC News |vauthors=Crawford A}}</ref> Nearly 6 million thalidomide pills were distributed throughout Brazil in this time period, and these cases have occurred despite the controls.<ref>{{Cite book | vauthors = Yasmin S |url=https://books.google.com/books?id=QrwLEAAAQBAJ&dq=million+thalidomide+Brazil&pg=PA132 |title=Viral BS: Medical Myths and Why We Fall for Them |date=2021-01-12 |publisher=JHU Press |isbn=978-1-4214-4041-5 |language=en}}</ref>

In 1998, the FDA approved the drug's use in the treatment of ENL.<ref name="nyt-fda">{{Cite news |date=17 July 1998 |title=Thalidomide Approved to Treat Leprosy, With Other Uses Seen |url=https://www.nytimes.com/1998/07/17/us/thalidomide-approved-to-treat-leprosy-with-other-uses-seen.html |url-status=live |archive-url=https://web.archive.org/web/20201203003055/https://www.nytimes.com/1998/07/17/us/thalidomide-approved-to-treat-leprosy-with-other-uses-seen.html |archive-date=3 December 2020 |access-date=8 January 2012 |work=New York Times |vauthors=Stolberg SG}}</ref> Because of thalidomide's potential for causing birth defects, the drug may be distributed only under tightly controlled conditions. The FDA required that [[Celgene Corporation]], which planned to market thalidomide under the brand name ''Thalomid'', establish a system for thalidomide education and prescribing safety (STEPS) oversight program. The conditions required under the program include limiting prescription and dispensing rights to authorized prescribers and pharmacies only, keeping a registry of all patients prescribed thalidomide, providing extensive patient education about the risks associated with the drug, and providing periodic pregnancy tests for women who take the drug.<ref name="nyt-fda" />

In 2010, the [[World Health Organization]] stated that it did not recommend thalidomide for leprosy due to the difficulty of adequately controlling its use, and due to the availability of [[clofazimine]].<ref>{{Cite web |last=Anon |title=Use of thalidomide in leprosy |url=https://www.who.int/lep/research/thalidomide/en/index.html |url-status=dead |archive-url=https://web.archive.org/web/20061110083549/http://www.who.int/lep/research/thalidomide/en/index.html |archive-date=10 November 2006 |access-date=22 April 2010 |website=WHO:leprosy elimination |publisher=WHO}}</ref>

===Cancer treatment===
Shortly after the teratogenic properties of thalidomide were recognized in the mid-1960s, its anti-cancer potential was explored and two clinical trials were conducted in people with advanced cancer, including some people with multiple myeloma; the trials were inconclusive.<ref name="Kyle">{{Cite journal |vauthors=Kyle RA, Rajkumar SV |date=March 2008 |title=Multiple myeloma |journal=Blood |volume=111 |issue=6 |pages=2962–72 |doi=10.1182/blood-2007-10-078022 |pmc=2265446 |pmid=18332230}}</ref>

Little further work was done with thalidomide in cancer until the 1990s.<ref name=Kyle/>

[[Judah Folkman]] pioneered studies into the role of [[angiogenesis]] (the proliferation and growth of blood vessels) in the development of cancer, and in the early 1970s had shown that [[solid tumors]] could not expand without it.<ref name="NASbio">{{Cite web |year=2014 |title=Judah Folkman: 1933–2008. A Biographical Memoir |url=http://www.nasonline.org/publications/biographical-memoirs/memoir-pdfs/folkman-judah.pdf |url-status=live |archive-url=https://web.archive.org/web/20200802184808/http://www.nasonline.org/publications/biographical-memoirs/memoir-pdfs/folkman-judah.pdf |archive-date=2 August 2020 |access-date=11 August 2015 |publisher=National Academy of Sciences |vauthors=Donahoe PK}}</ref><ref name="Beilenberg">{{Cite journal |vauthors=Bielenberg DR, D'Amore PA |year=2008 |title=Judah Folkman's contribution to the inhibition of angiogenesis |journal=Lymphatic Research and Biology |volume=6 |issue=3–4 |pages=203–7 |doi=10.1089/lrb.2008.1016 |pmid=19093793}}</ref> In 1993 he surprised the scientific world by hypothesizing the same was true of [[blood cancers]],<ref name="Folkman">{{Cite journal |vauthors=Folkman J |date=December 2001 |title=Angiogenesis-dependent diseases |journal=Seminars in Oncology |volume=28 |issue=6 |pages=536–42 |doi=10.1016/s0093-7754(01)90021-1 |pmid=11740806}}</ref> and the next year he published work showing that a [[biomarker]] of angiogenesis was higher in all people with cancer, but especially high in people with blood cancers, and other evidence emerged as well.<ref>{{Cite journal |vauthors=Ribatti D |year=2008 |title=Judah Folkman, a pioneer in the study of angiogenesis |journal=Angiogenesis |volume=11 |issue=1 |pages=3–10 |doi=10.1007/s10456-008-9092-6 |pmc=2268723 |pmid=18247146}}</ref>  Meanwhile, a member of his lab, Robert D'Amato, who was looking for [[angiogenesis inhibitors]], discovered in 1994 that thalidomide inhibited angiogenesis<ref>{{Cite journal |vauthors=D'Amato RJ, Loughnan MS, Flynn E, Folkman J |date=April 1994 |title=Thalidomide is an inhibitor of angiogenesis |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=91 |issue=9 |pages=4082–5 |bibcode=1994PNAS...91.4082D |doi=10.1073/pnas.91.9.4082 |pmc=43727 |pmid=7513432 |doi-access=free}}</ref> and was effective in suppressing tumor growth in rabbits.<ref>{{Cite journal |vauthors=Verheul HM, Panigrahy D, Yuan J, D'Amato RJ |date=January 1999 |title=Combination oral antiangiogenic therapy with thalidomide and sulindac inhibits tumour growth in rabbits |journal=British Journal of Cancer |volume=79 |issue=1 |pages=114–8 |doi=10.1038/sj.bjc.6690020 |pmc=2362163 |pmid=10408702}}</ref> Around that time, the wife of a man who was dying of multiple myeloma and whom standard treatments had failed, called Folkman asking him about his anti-angiogenesis ideas.<ref name=Beilenberg/>  Folkman persuaded the patient's doctor to try thalidomide, and that doctor conducted a clinical trial of thalidomide for people with multiple myeloma in which about a third of the subjects responded to the treatment.<ref name=Beilenberg/>  The results of that trial were published in the New England Journal of Medicine in 1999.<ref name=Beilenberg/><ref name="nejm-myeloma">{{Cite journal |vauthors=Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar M, Zeddis J, Barlogie B |date=November 1999 |title=Antitumor activity of thalidomide in refractory multiple myeloma |journal=The New England Journal of Medicine |volume=341 |issue=21 |pages=1565–71 |doi=10.1056/NEJM199911183412102 |pmid=10564685 |doi-access=free}}</ref>

After further work was done by Celgene and others, in 2006 the US&nbsp;Food and Drug Administration granted accelerated approval for thalidomide in combination with dexamethasone for the treatment of newly diagnosed [[multiple myeloma]] patients.<ref name=Beilenberg/><ref>{{Cite web |title=FDA Approval for Thalidomide |url=http://www.cancer.gov/cancertopics/druginfo/fda-thalidomide |url-status=dead |archive-url=https://web.archive.org/web/20120128120343/http://www.cancer.gov/cancertopics/druginfo/fda-thalidomide |archive-date=28 January 2012 |access-date=8 January 2012 |publisher=National Cancer Institute}}</ref>

It was also evaluated whether thalidomide can be combined with melphalan and prednisone for patients with multiple myeloma. This combination of drugs probably increases the overall survival.<ref>{{Cite journal |vauthors=Piechotta V, Jakob T, Langer P, Monsef I, Scheid C, Estcourt LJ, Ocheni S, Theurich S, Kuhr K, Scheckel B, Adams A, Skoetz N |date=November 2019 |title=Multiple drug combinations of bortezomib, lenalidomide, and thalidomide for first-line treatment in adults with transplant-ineligible multiple myeloma: a network meta-analysis |journal=The Cochrane Database of Systematic Reviews |volume=2019 |issue=11 |doi=10.1002/14651858.CD013487 |pmc=6876545 |pmid=31765002 |collaboration=Cochrane Haematology Group}}</ref>