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What is thalidomide (Thalidomide®)?

According to the European Medicines Agency (EMA), thalidomide is approved in patients with multiple myeloma who have not been treated for this disease before and who are older than 65 or younger if they cannot be treated with anticancer chemotherapy.

Thalidomide is a medicine which can modulate the activity of the immune system (immunomodulation). It blocks the development of cancer cells, and stimulates the body’s defence mechanisms.

As multiple myeloma is considered a ‘rare disease’ because of the small number of patients with this disease, thalidomide has the designation of ‘orphan medicine’ because it is used in a rare disease.

How does thalidomide work?

Thalidomide and its analogues — lenalidomide and pomalidomide, so far — are a group of medicines used in the treatment of multiple myeloma. They work by modulating some activities of the immune system.

Thalidomide modulates the action of the immune system in several ways, of which the best known are:

  • It reduces the production by immune cells of a substance (a cytokine) called tumour necrosis factor (TNF-α) and of other pro-inflammatory cytokines which can promote the growth of cancer cells.
  • It reduces a process called angiogenesis, consisting of the generation of new blood vessels, which promotes the growth of tumours.
  • It induces the death of myeloma cells.

Thalidomide is indicated by the EMA in the treatment of multiple myeloma in combination with two more anti-cancer medicines — melphalan and prednisone — for patients with myeloma who have not been treated for this disease before and who are older than 65 or younger if they cannot be treated with anti-cancer chemotherapy. And this combination is one of the standards of care for transplant-ineligible patients (another possible combination is bortezomib, melphalan and prednisone).

In addition, thalidomide can be used as recommended by the European Myeloma Network in: 1) induction therapy — to increase the response before an autologous stem cell transplantation — in a triple combination of bortezomib, thalidomide and dexamethasone, 2) maintenance therapy after autologous stem cell transplantation, in a combination of bortezomib, thalidomide and dexamethasone.

Thalidomide is also used in patients previously treated with other therapies not effective against multiple myeloma.

Side-effects of thalidomide

Thalidomide produces congenital malformations. It is absolutely contraindicated in pregnant women or in women who may become pregnant. You should consult your doctor if you are or think that you may be pregnant.

Sedation is one of the most frequent side-effects, so thalidomide is taken at night.

Constipation is very common. It can be often controlled by a combination of generous fluid intake, stool softeners, and laxatives.

Dry skin and itching are frequently noted. They can be prevented by using non-alcohol-based lubricants and by avoiding hot baths. Occasionally, a true skin rash occurs — which requires a temporary cessation of thalidomide, with resumption at a lower dose.

Tingling, pain and numbness in the hands and feet (sensorimotor peripheral neuropathy) may occur, particularly after taking thalidomide for long periods.

Less common side-effects include swelling in the legs, shaking, slowing of the heartbeat or a reduction of the thyroid hormones.

Reduction of a type of white blood cells called neutrophils or impaired liver function are very rare side-effects.

When thalidomide is used together with melphalan and prednisone, the most common side-effects are reduction of the level of some white blood cells such as neutrophils or lymphocytes, or of red blood cells (anaemia) or platelets; and tingling, pain and numbness in the hands and feet, shaking, dizziness, unusual sensations like pins and needles (paraesthesia), reduced sense of touch, sleepiness, constipation or swelling in the legs.

How and when is thalidomide given?

The recommended dose of thalidomide is four capsules a day (i.e., 200 mg, because each capsule contains 50 mg), taken at the same time, preferably at bedtime. In patients over 75 years of age a starting dose of two capsules (100 mg) a day is recommended.

Thalidomide can be used for a maximum of 12 treatment cycles, with each cycle lasting six weeks. The doctor may delay, reduce or stop doses if the patient experiences certain side-effects.

Patients also receive an anticoagulant (a medicine to prevent the formation of blood clots) for at least the first five months of treatment.

References

  • Thalidomide Celgene. EPAR summary for the public. EMA/740933/20115. EMEA/H/C/000823 [Internet]. [cited 2016 Sep 26]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/000823/WC500037052.pdf
  • Lists of medicinal products for rare diseases in Europe. Orphanet Report Series. October 2016 [Internet]. [cited 2016 Dec 5]. Available from: http://www.orpha.net/orphacom/cahiers/docs/GB/list_of_orphan_drugs_in_europe.pdf
  • Weber D. Thalidomide and its derivatives: new promise for multiple myeloma. Cancer Control. 2003;10(5):375–383.
  • Engelhardt M, Terpos E, Kleber M, Gay F, Wasch R, Morgan G, et al. European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma. Haematologica. 2014;99(2):232–42.
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