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Thalidomide monotherapy

Synopsis

Historical Background of Thalidomide

Originally developed and marketed in the late 1950s as a sedative and remedy for morning sickness in pregnant women, thalidomide led to catastrophic birth defects when taken during pregnancy. Due to these teratogenic effects, its usage was banned in many countries by the early 1960s.

Rediscovery and Anticancer Properties

During the late 1990s, the anti-angiogenic and immunomodulatory effects of thalidomide were explored. Researchers hypothesized that these properties could be harnessed against cancers that rely on angiogenesis.

Singhal et al., 1999 ([1] Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma. New England Journal of Medicine. 1999;341:1565-71): This seminal study reported the effects of thalidomide in patients with refractory multiple myeloma. Thalidomide showed significant antitumor activity, leading to renewed interest in the drug.

Development of Analogues

The success of thalidomide spurred the development of its analogues, designed to retain its therapeutic benefits while minimizing side effects. Lenalidomide and pomalidomide are two such analogues that have shown significant efficacy in multiple myeloma with a better side effect profile.

Current Role in Therapy

While newer agents and combinations have emerged in the treatment landscape of multiple myeloma, thalidomide and its derivatives remain vital components in various treatment regimens, especially in certain settings and geographies.

Conclusion

The repositioning of thalidomide for multiple myeloma is a testament to the importance of re-evaluating existing drugs for new therapeutic indications. Its successful transition from a notorious drug to a vital component in the multiple myeloma treatment arsenal underscores the ever-evolving nature of drug development and therapy.
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Regimen

Study	Dates of enrollment	Evidence
Singhal et al. 1999	1997-1998	Non-randomized

Targeted therapy

• Thalidomide (Thalomid) 200 mg PO once per day, increased by 200 mg every two weeks for six weeks, to final dose of 800 mg per day

Continued indefinitely

References

1. Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar M, Zeldis J, Siegel D, Crowley J, Barlogie B. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999 Nov 18;341(21):1565-71. Erratum in: N Engl J Med 2000 Feb 3;342(5):364. link to original article contains dosing details in abstract PubMed
2. Yakoub-Agha I, Mary JY, Hulin C, Doyen C, Marit G, Benboubker L, Voillat L, Moreau P, Berthou C, Stoppa AM, Maloisel F, Rodon P, Dib M, Pegourie B, Casassus P, Slama B, Damaj G, Zerbib R, Harousseau JL, Mohty M, Facon T; Intergroupe Francophone du Myélome (IFM). Low-dose vs. high-dose thalidomide for advanced multiple myeloma: a prospective trial from the Intergroupe Francophone du Myélome. Eur J Haematol. 2012 Mar;88(3):249-59. Epub 2012 Jan 4. link to original article PubMed