Overview of drug therapy for multiple myeloma.
BACKGROUND
Multiple myeloma accounts for 10% of all haematologic malignancies worldwide. In Europe, over 10,000 new cases and nearly 8000 deaths were attributed to multiple myeloma in 2000. Unlike other malignancies, in which surgery and radiation are important treatment modalities, myeloma is exclusively treated with stem cell transplantation and drug therapy, requiring pharmacists to stay abreast of new developments. The melphalan-prednisolone and vincristine-doxorubicin-dexamethasone (VAD) regimens, which have been standard treatments for multiple myeloma over the past few decades, have yielded responses without real survival benefits. Transplantation utilizing high-dose chemotherapy has produced the only meaningful survival benefits for patients with multiple myeloma, but many patients are not candidates for this aggressive treatment option. More effective therapies for multiple myeloma are needed.


OBJECTIVE
To address the mechanisms of action, safety, and efficacy of novel approaches to the treatment of myeloma involving bortezomib, thalidomide and its analogues, lenalidomide and CC-4047 (Actimid), and arsenic trioxide as single agents or in combination regimens.


METHODS
Published preclinical and primary clinical trial results, as well as scientific or clinical meeting abstracts. The author determined the relevance and subsequent inclusion of the data.


CONCLUSIONS
Bortezomib is approved in the US and Europe as single-agent therapy for the treatment of relapsed or refractory multiple myeloma. Thalidomide, its analogues, and arsenic trioxide have demonstrated activity and are under investigation in this disease. Further clinical trials of the efficacy and toxicity of these novel agents are ongoing and will further define optimal combinations and sequencing with conventional therapies.
Saunders
Geoff
G
geoff.saunders@manchester.nhs.uk
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001897:Boronic Acids / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000069286:Bortezomib; D002986:Clinical Trials as Topic; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism; D009194:Myeloma Proteins / Q000378:metabolism; D010087:Oxides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011719:Pyrazines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013792:Thalidomide / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001152:Arsenicals; D001897:Boronic Acids; D009194:Myeloma Proteins; D010087:Oxides; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D000077237:Arsenic Trioxide