Treatment and Course of Multiple Myeloma
My mother (72 years old) has had multiple myeloma for about 7 years and most recently was treated with thalidomide. The thalidomide makes her feel woosy. What are the next options for treatment? What can I expect her course to be? She has bone pain and also did not like how she felt on Prednisone earlier in her treatment.
Multiple myeloma (MM) is the second most common cancer of the blood after non-Hodgkin’s lymphoma. It is a cancer of the plasma cells, which normally produce antibodies to help fight infection and disease. The median age at diagnosis is 68 years. There is no known cure, and the median survival with intensive treatment is 3-5 years. In the United States approximately 45,000 people are living with MM and an estimated 14,600 new cases are diagnosed each year. Current treatments include steroids, chemotherapy, and stem cell transplantation. Thalidomide and bortezomib are two promising new treatments. Other experimental treatments may also be available via research protocols.
Thalidomide was introduced as a sedative agent in Europe in the 1950`s. It was found to be particularly effective for treating morning sickness, but the children born to women who used it for this purpose developed birth defects. It was removed from the market in 1961. The drug’s sedative effects are most likely responsible for the woozy feeling you report. This effect may abate with continued use. In addition to its sedative effects, thalidomide has demonstrated effects on the immune system, and this is the reason it is used to treat multiple myeloma (MM). It has been used alone and in combination with dexamethasone to treat a number of diverse diseases including HIV, graft versus host disease, and some solid and hematological cancers. Some authors view thalidomide treatment as one of the most significant improvements in the care of MM in the last 20 years. Several mechanisms of action for the beneficial effect of thalidomide in MM have been proposed, but the exact effect of thalidomide is unknown. The overall response rate to thalidomide in the treatment of relapsed or refractory MM is around 36% with a median duration of response of greater than 12 months. The optimal dose has not yet been determined. However, most patients respond to doses in the range of 200-400mg daily. In addition to drowsiness, blood clots (venous thromboembolism VTE) have been reported in about 4-5 % of patients taking thalidomide alone. Other side effects include tingling and numbness in the hands and feet, which can be permanent if not caught early, and constipation.
Addition of dexamethasone may improve the response rate in patients with relapsed or refractory MM to as high as 69%, but the available data is from small studies. Further study is needed to determine the true response rate and duration of activity of this combination therapy. Some authors recommend that the combination of dexamethasone and thalidomide should only be used in newly diagnosed patients within the context of a clinical trial. The rate of VTE jumps to around 15% of patients when a combination of thalidomide and dexamethasone is used.
In May 2003 the Food and Drug Administration (FDA) approved a new drug called bortezomib (VelcadeÂ®). Bortezomib is indicated for the treatment of multiple myeloma patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy. Approval was based on the performance of bortezomib in two studies. In both studies, patients with MM who failed prior therapy or relapsed were given the drug. Response rates were between 35 and 50% with approximately 4% of patients achieving a complete response defined as no detectable myeloma protein. Median duration of response was 12 months and median survival was 16 months. The most common adverse events reported with bortezomib include nausea (64%), diarrhea (51%), constipation (43%), decreased platelets (43%), decreased red blood cells (32%), and numbness and tingling, and occasionally pain in the hand and feet (37%). Other side effects have also been reported.
Bortezomib is metabolized by several of the cytochrome p450 enzymes. Other medicines that stimulate or block the activity of these enzymes are likely to interact with bortezomib. Bortezomib can also inhibit one of the P450 enzymes, which could result in higher than expected blood levels of some medicines. However, to date, no drug interactions have been reported. Some patients taking medicines to treat diabetes reported elevated or decreased blood sugar when they took bortezomib. Bortezomib is available in 3.5mg vials with an average wholesale price of $1094 per vial. The recommended dosage is 1.3mg/M2 (about one vial) on days 1,4,8, and 11 followed by a 10-day rest period. This 21 day cycle can be repeated, and an average course of treatment consisting of 5.5 cycles will cost about $24,000. A patient assistance program is available. For information about Velcade Â® reimbursement assistance call 866-VELCADE.
Bone pain and fractures, especially in the chest and back are common complaints in patients with MM. Radiological evidence of bone loss or fractures is present in approximately 80% of MM patients at diagnosis. A number of chemicals released by MM cells cause the bone loss. Medicines called bisphosphonates may to reduce or reverse bone loss. Pamidronate (ArediaÂ®), and Zoledronic acid (ZometaÂ®) are bisphosphonates. A recent clinical practice guideline from the American Society of Clinical Oncology recommends intravenous use of either pamidronate or zoledronic acid for patients with X-ray evidence of lytic bone loss.
The decision to use a particular medicine in a particular patient depends on the expertise and judgement of the treating physician. The doctor treating your mother’s MM will be up to date on the various medicines used to treat MM and will be able to tell you whether use of a particular medicine is appropriate.
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