These guidelines require validation by ongoing clinical trials; participation in clinical trials is the preferred choice, when possible.
Since the mid-1980s, dexamethasone has been administered at a dose of 40 mg orally for 4 consecutive days, which is the same schedule used with the vincristine plus doxorubicin plus dexamethasone (VAD) regimen. Response rates of 60% to 70% in previously untreated patients appeared to be as high as those in patients treated with VAD.[13,14][Level of evidence: 3iiiDiv]
A prospective trial randomly assigned 488 patients older than 65 years to receive dexamethasone alone, melphalan plus dexamethasone, dexamethasone plus interferon-alpha, and melphalan plus prednisone (MP).
- With a median follow-up of 7.1 years, no difference was observed in overall survival (OS) (median survival times were 32 months-40 months).[Level of evidence: 1iiA]
- The patients on the dexamethasone-based arms had significantly more infections, glucose intolerance, gastrointestinal symptoms, and psychiatric complaints. (Refer to the PDQ summary on Gastrointestinal Complications for more information on gastrointestinal symptoms.)
There has never been a randomized trial comparing single-agent oral dexamethasone at a traditional high dose (40 mg a day for 4 days, repeated after 4 days off) with a lower dose (≤40 mg weekly). This issue of dexamethasone dose has been evaluated in two of the following prospective, randomized trials:
- In the context of melphalan, as evaluated in a National Cancer Institute of Canada trial (CAN-NCIC-MY7).
- Compared with standard-dose steroids, high-dose dexamethasone was associated with an increased risk of infection in the melphalan trial, but there was no difference in efficacy.
- In the context of lenalidomide, as evaluated in an Eastern Cooperative Oncology Group trial (ECOG-E4A03).
- The lenalidomide study questioned the safety and efficacy of high-dose dexamethasone. (Refer to the Lenalidomide section of this summary for more information.)
Almost all ongoing clinical trials in the United States and Europe have implemented the low-dose dexamethasone schedule with or without other therapeutic agents.
IMiDs (immunomodulatory drugs)
Eleven randomized prospective studies involving more than 4,600 patients have examined the introduction of thalidomide as induction therapy for previously untreated symptomatic patients with multiple myeloma.[17,18,19,20,21,22,23,24,25,26]
- All of the trials reported improved response rates with the introduction of thalidomide and no hematopoietic damage, allowing adequate stem cell collection when applicable or allowing combinations with other myelosuppressive agents.
- Only two of the eleven randomized studies reported a survival advantage using thalidomide. In these trials, the patients older than 65 or 75 years at the 2-year follow-ups showed a 44- to 56-month median OS for MP plus thalidomide versus 28- to 30-month median OS for MP (P < .03 in both studies).[23,27][Level of evidence: 1iiA]
- A possible explanation is that the two trials used a lower dose of thalidomide than the other studies (100 mg vs. ≥200 mg), a lower dose of steroids (60 mg of prednisone vs. high-dose dexamethasone), and involved the use of alkylating agents.