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`[Results of treatment of patients with advanced multiple myeloma with the vincristineadriamycindexamethasone protocol]. PubMed NCBI
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`PubMed
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`Format: Abstract
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`Srp Arh Celok Lek. 1996 NovDec;124(1112):2926.
`[Results of treatment of patients with advanced multiple myeloma
`with the vincristineadriamycindexamethasone protocol].
`[Article in Serbian]
`Marisavljević D, Bosković D, Radosević N, Elezović I, Tomin D, Gotić M, Antunović P.
`
`Abstract
`A very few treatment regimens have shown a benefit in patients with multiple myeloma resistant to
`conventional melphalan/prednosone therapy or similar combinations. The first "biologically designed"
`protocol for the treatment of advanced, refractory myeloma was a combination of vincristine,
`doxorubicin and intermittent highdose dexamethasone, so called VAD regimen. This report
`summarizes our experience in VAD regimen in the treatment of advanced, refractory myeloma
`patients, initially treated with melphalanbased chemotherapy.
`METHODS:
`Between July 1989 and July 1995, 27 patients with hightumourmass stage (Durie
`Salmon staging system) of the disease were treated with VAD combination. Clinical characteristics of
`patients are shown in Table 1. There were 17 pts who never responded (9 pts) of who progressed
`during induction therapy (8 pts). The second group of 10 pts responded to induction therapy and
`relapsed. Five pts (four with progressive and one with resistant myeloma) were treated with VAD
`therapy particularly due to significant extramedullary infiltrates. All pts in this study were initially
`treated with VMCP induction therapy. Seven of them were additionally treated with ABP combination,
`and this subgroup of pts was characterized as "resistant to melphalan and doxorubicin". The VAD
`regimen consisted of fourday continuous infusions of vincristine (0.4 mg per day) and doxorubicin (9
`mg/m2 per day) in addition to dexamethasone in a dose of 40 mg for four days, beginning od days
`1.9 and 17 of each cycle. The response was defined as a reduction of serum myelomaprotein
`concentration exceeding 75 per cent, with disappearance of BenceJones protein excretion.
`RESULTS:
`"Good" response to VAD regimen was achieved in 12 of 27 pts (44 per cent), mainly after
`three cycles of chemotherapy (Table 2). The tumour reduction occurred rapidly (Table 3), without
`significant myelosuppression. Responserate was significantly higher in relapsing myeloma pts than
`in pts with progressive or resistant disease (chi 2 = 4.2; p < 0.05). Neither previous treatment (Table
`2) nor the type or paraprotein concentration, degree of marrow infiltration and cytologic type of
`plasma cells affected the response to VAD. Among 15 pts with "bad" response to VAD, seven died
`during first four months of treatment. All pts with significant extramedullary infiltrates failed to
`respond to VAD (chi 2 = 4.91; p < 0.05). Median survival of all pts was 16 months. In responsive pts
`remissions were of good quality and survival was significantly longer that that in whom treatment
`failed (Figure 1, left). In responsive pts the median duration of "plateauphase" was 11 months
`(Figure 1, right). In three pts who relapsed after the treatment, reinstitution of VAD regimen restored
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`https://www.ncbi.nlm.nih.gov/pubmed/9132962
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`ALVOGEN, Exh. 1033, p. 0001
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`11/20/2017
`[Results of treatment of patients with advanced multiple myeloma with the vincristineadriamycindexamethasone protocol]. PubMed NCBI
`the "plateauphase". The most important complications of treatment with VAD combination were
`infections (8 pts) but, fortunately, serious forms (i.e. pneumonia) were observed only in two pts.
`DISCUSSION:
`The antitumour effect of VAD regimen originates from a combined effect of doxorubicin
`and vincristine continuous infusions and intermittent pulses of highdose corticosteroids. The
`rationale for protracted administration of vincristine and doxorubicin was based on long generation
`time and low growth fraction of plasma cells in most patients, while the use of highdose
`dexamethasone was based on wellknown dosedepend antimyeloma effect of corticosteroids. Using
`this chemotherapy schedule, significant prolongation of survival was achieved in our responding
`patients comparing to patients with VADresistant myeloma. The major toxic effect of treatment was
`infection, which was attributed in part to intensive steroid program. Relapse of the disease could be
`expected about one year after completion of VAD therapy. Nevertheless, the second "plateauphase"
`can be obtained upon reinitiation of VAD (ABSTRACT TRUNCATED).
`
`PMID: 9132962
`[Indexed for MEDLINE]
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`https://www.ncbi.nlm.nih.gov/pubmed/9132962
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`2/2
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`ALVOGEN, Exh. 1033, p. 0002
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