Thalidomide-based regimens
Thalidomide was first used in the late 1950s for the treatment of morning sickness in pregnant women and as a sedative to treat insomnia. It was withdrawn in 1961 after it was found to cause severe birth-defects which affected the growth of limbs (phocomelia). This was thought to happen because of the anti-angiogenic properties of thalidomide, which prevented the formation of new blood vessels.
Since that time, thalidomide has been used cautiously in the treatment of various medical conditions related to the immune system, and much has been learned about how it works and how its potential side effects can be managed.
In recent years, thalidomide has been widely used as a treatment for different types of cancer, particularly myeloma.
Efficacy
Once used as a monotherapy, thalidomide is now almost always used in combination with an alkylating agent and a steroid.
Combinations of thalidomide containing treatment regimens for newly-diagnosed older and/or less fit myeloma patients include:
- Cyclophosphamide, thalidomide and dexamethasone (CTD)
Data from the national Myeloma IX trial showed that the combination of cyclophosphamide and reduced (attenuated) doses of thalidomide and dexamethasone produced response rates of 64% in older and/or less fit patients treated in the non-intensive arm of the trial - Melphalan, prednisolone and thalidomide (MPT)
At least five large international clinical trials demonstrated a significant benefit of MPT over MP. The combination of MPT was associated with response rates of approximately 70% compared to MP which produced response rates of approximately 40%
Administration
Thalidomide is taken as a single oral dose at bedtime, to reduce the impact of somnolence. The optimal dose, administration schedule and duration of treatment depends on both the clinical and individual situation of the patient. It is usually given daily over a 6-week cycle for up to 12 cycles.
Side effects
| Treatment | Potential side effects |
|---|---|
| Cyclophosphamide / melphalan | Nausea and vomiting, diarrhoea, hair loss, weight loss, sore mouth, infections, fatigue, anaemia, skin rash, infertility |
| Thalidomide | Somnolence, peripheral neuropathy, venous-thromboembolism (VTE), anaemia, fatigue, constipation, skin rashes |
| Dexamethasone/ prednisolone | Stomach irritation, increased appetite, fluid retention, swelling in feet and hands, changes in blood sugar levels, infections, mood swings, insomnia, muscular problems, osteoporosis |
Nurses should stress to patients the importance of early reporting of any side effects. In particular, they should ensure patients are aware of peripheral neuropathy. This is a potentially irreversible side effect that is particularly common after prolonged thalidomide exposure or in those with pre-existing neuropathy due to other treatments or co-morbidities, such as diabetes. Patients should be informed of what to look out for and to let their nurse or doctor know immediately if any symptoms develop.
There is also an increased risk of thromboembolic events with any treatment combination incorporating an immunomodulatory drug with a steroid. Both BSH and IMWG have guidelines recommending the use of prophylaxis for myeloma patients based on individual risk factors. Nurses should be aware that all patients who are due to start thalidomide should undergo a risk assessment for venous thromboembolism (VTE) and be prescribed anti-coagulation medications as required.
Read more about how to help manage the risk of VTEs and manage peripheral neuropathy in our Myeloma Nurse Guides.