Alexanian R, Barlogie B, Tucker SVAD-based regimens as primary treatment for multiple myeloma. Am J Hematol 33(2): 86-88

University of Texas, M.D. Anderson Cancer Center, Houston 77030.
American Journal of Hematology (Impact Factor: 3.8). 02/1990; 33(2):86-9. DOI: 10.1002/ajh.2830330203
Source: PubMed


An alternating VCAD-VAD regimen, combining vincristine-doxorubicin by continuous infusion with cyclophosphamide and pulse dexamethasone, or VAD alone, was given to 175 previously untreated patients with multiple myeloma. The response rate with primary VAD-based regimens of 55% was virtually identical to the 54% in comparable patients treated previously with similar programs by using bolus vincristine-doxorubicin. Despite responses to VAD that were more rapid in onset than any previous treatment, remission and survival times were similar. This may be due to major differences in drug sensitivity between progenitor and differentiated plasma cells. A VAD-based regimen seems better for newly diagnosed patients when rapid control of multiple myeloma is necessary.

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    • "Several different combination regimens have been applied for the treatment of multiple myeloma. Especially, VAD regimen (vincristine (V) + doxorubicin (A) + dexamethasone (D)) is known as an efficient treatment that induces a more rapid response than other regimens for multiple myeloma [36, 37]. However, serious side effects such as myelotoxicity, neurotoxicity, and nausea still remain problematic for multiple myeloma treatment [38]. "
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    ABSTRACT: Background. Combination cancer therapy is one of the attractive approaches to overcome drug resistance of cancer cells. In the present study, we investigated the synergistic effect of decursin from Angelica gigas and doxorubicin on the induction of apoptosis in three human multiple myeloma cells. Methodology/Principal Findings. Combined treatment of decursin and doxorubicin significantly exerted significant cytotoxicity compared to doxorubicin or decursin in U266, RPMI8226, and MM.1S cells. Furthermore, the combination treatment enhanced the activation of caspase-9 and -3, the cleavage of PARP, and the sub G1 population compared to either drug alone in three multiple myeloma cells. In addition, the combined treatment downregulated the phosphorylation of mTOR and its downstream S6K1 and activated the phosphorylation of ERK in three multiple myeloma cells. Furthermore, the combined treatment reduced mitochondrial membrane potential, suppressed the phosphorylation of JAK2, STAT3, and Src, activated SHP-2, and attenuated the expression of cyclind-D1 and survivin in U266 cells. Conversely, tyrosine phosphatase inhibitor pervanadate reversed STAT3 inactivation and also PARP cleavage and caspase-3 activation induced by combined treatment of doxorubicin and decursin in U266 cells. Conclusions/Significance. Overall, the combination treatment of decursin and doxorubicin can enhance apoptotic activity via mTOR and/or STAT3 signaling pathway in multiple myeloma cells.
    Full-text · Article · May 2013 · Evidence-based Complementary and Alternative Medicine
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    • "In recent years, there have been major advances in the treatment of multiple myeloma, due to new agents, superior drug combinations, and widespread use of intensive therapy supported by autologous stem cells [1] [2] [3] [4] [5]. Thus, remission of disease has been achieved in 85–90% of currently treated patients, including 30–40% with complete remission (CR) [5] [6] [7] [8]. "
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    ABSTRACT: Among 792 patients with multiple myeloma treated from 1987 to 2010 and assessed after 18 months, there were 167 patients with complete remission. For those 60 patients treated between 1987-1998 and with long followup, the latest relapse occurred after 11.8 years, so that 13 patients have remained in sustained complete remission for longer than 12 years (range 12-22 years). These results suggest that 3% of all patients treated during that period may be cured of multiple myeloma. In addition to immunofixation, more sensitive techniques for the detection of residual disease should be applied more consistently in patients with apparent complete remission in order to identify those with potential cure.
    Full-text · Article · May 2012
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    • "spread use in the front-line setting (Alexanian et al, 1990). However, this anthracycline is associated with significant cardiotoxicity. "
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    ABSTRACT: The combination of pegylated liposomal doxorubicin (PLD), bortezomib and dexamethasone has shown efficacy in the treatment of multiple myeloma (MM) patients. Our earlier retrospective study suggested that modification of the doses, schedules and route of administration of these drugs appears to reduce toxicity without compromising anti-MM activity. As a result, we evaluated this modified drug combination in the frontline setting in a prospective multicentre phase II trial. Thirty-five previously untreated MM patients were enrolled. Dexamethasone IV 40 mg, bortezomib 1 mg/m(2) and PLD 5 mg/m(2) were administered on days 1, 4, 8 and 11 of a 4-week cycle. Patients were treated to their maximum response plus two additional cycles. The treatment regimen was discontinued after a maximum of eight cycles. Our modified schedule and dosing regimen achieved a high overall response rate of 86%, while showing a marked decrease in the incidence and severity of peripheral neuropathy, palmar-plantar erythrodysesthesia and myelosuppression compared to the standard dosing on a 3-week cycle using these drugs. This modified regimen of dexamethasone, bortezomib and PLD shows improved tolerability and safety while maintaining a high response rate when compared to standard treatment with these agents in the frontline setting.
    Full-text · Article · Sep 2011 · British Journal of Haematology
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