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Thalomid
• Relapsed and Refractory Myeloma, Combination Therapy
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Thalidomide has been tested in numerous combination therapies with good results. This section will examine the more common combinations.
Patients who fail to respond to standard chemotherapy and autologous transplant (AT) are an especially difficult subgroup to treat effectively, and no ideal therapy has yet been identified. Investigators in Italy evaluated the combination of thalidomide and dexamethasone and found it to produce significantly greater therapeutic response after relapse and post-AT, compared to other therapies containing combinations of doxorubicin, cyclophosphamide, etoposide and cisplatin (Palumbo, 2004). The response rate to thal-dex was 19% near complete remission, 28% partial remission, and 35% stable disease, while the rates for salvage chemotherapy were 16% partial response, 32% stable disease, and the majority (53%) had progressive disease. These findings suggest that thal-dex is a superior salvage therapy to standard follow-up chemotherapy in patients who fail a first course of high-dose chemotherapy and AT.
Patients who cannot tolerate high dose therapy with thal-dex may still be able to take the combination with lower doses of thalidomide, particularly when combined with a third agent. Many of these studies are summarized in the next section.
Response rates to thal-dex reported from selected studies are summarized in the table below.
In Combination with Dexamethasone
The combination of thalidomide and dexamethasone appears to be a very effective therapy for relapsed and refractory myeloma. Patients who don't respond to thalidomide alone often respond to the combination. With thalidomide and dexamethasone, 50% reductions in M protein or more have been achieved in 48% to 78% of patients in recent trials, which are summarized in the table below.
Patients who fail to respond to standard chemotherapy and autologous transplant (AT) are an especially difficult subgroup to treat effectively, and no ideal therapy has yet been identified. Investigators in Italy evaluated the combination of thalidomide and dexamethasone and found it to produce significantly greater therapeutic response after relapse and post-AT, compared to other therapies containing combinations of doxorubicin, cyclophosphamide, etoposide and cisplatin (Palumbo, 2004). The response rate to thal-dex was 19% near complete remission, 28% partial remission, and 35% stable disease, while the rates for salvage chemotherapy were 16% partial response, 32% stable disease, and the majority (53%) had progressive disease. These findings suggest that thal-dex is a superior salvage therapy to standard follow-up chemotherapy in patients who fail a first course of high-dose chemotherapy and AT.
Patients who cannot tolerate high dose therapy with thal-dex may still be able to take the combination with lower doses of thalidomide, particularly when combined with a third agent. Many of these studies are summarized in the next section.
Response rates to thal-dex reported from selected studies are summarized in the table below.
Summary of Recent Combination Thalidomide-Dexamethasone Trials in Relapsed and Refractory Myeloma |
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*CR = complete response (typically defined as the absence of M protein); NCR = near complete response (typically defined as a ≥90% reduction in M protein) Major R = major response (typically defined as a ≥75% reduction in M protein); PR = partial response (typically defined as ≥50% reduction in M protein); SD = stable disease Minor R = minor response (typically defined as <50% reduction in M protein) PFS = progression free survival OS = overall survival IMMW = International Multiple Myeloma Workshop |
In Combination with Chemotherapy
Combining chemotherapy with thalidomide may increase the antitumor effects compared with either strategy alone. When thalidomide is used in combination with chemotherapy, responses (defined as a 25% reduction in M protein or more) have been achieved in 30% to 80% of patients.
Various thalidomide-containing drug regimens have been evaluated in relapsed and refractory disease, including:
- Cyclophosphamide, dexamethasone, thalidomide (CDT)
- Cyclophosphamide, thalidomide, etoposide, dexamethasone (CTED)
- Dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, etoposide (DT-PACE)
- Doxil® (liposomal doxorubicin, Ortho Biotech), vincristine, dexamethasone, thalidomide (DVd-T)
- Vincristine, Adriamycin® (doxorubicin), dexamethasone, thalidomide (VAD-T)
- Velcade® (bortezomib, Millennium), thalidomide
- Melphalan, thalidomide, dexamethasone (MTD)
- Cyclophosphamide, thalidomide and prednisone (CTP)
Summary of Recent Combination Thalidomide-Chemotherapy Trials in Relapsed and Refractory Myeloma |
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*CR = complete response (typically defined as the absence of M protein); NCR = near complete response (typically defined as a ≥90% reduction in M protein); Major R = major response (typically defined as a ≥75% reduction in M protein); PR = partial response (typically defined as ≥50% reduction in M protein); Minor R = minor response (typically defined as <50% reduction in M protein) SD = Stable disease ASH = American Society of Hematology meeting. IMMW = International Multiple Myeloma Workshop |
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Other small studies have shown good results with low-dose thalidomide with dexamethasone in combinations with agents such as zoledronic acid (zdT) (Teoh et al, 2004).