Evidence that multiple myeloma may be regulated by homeostatic control mechanisms: correlation of changes in the number of clonogenic myeloma cells in vitro with clinical response

Maitland, J.; Millar, Barbara C.; Bell, Jo; Montes, A.; Treleaven, J; Gore, Martin; McElwain, T. J.

doi:10.1038/bjc.1990.94

Cited by 10 publications

(4 citation statements)

References 12 publications

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“…5 Preclinical data suggest that cyclophosphamide may enhance the efficacy of VAD-based chemotherapeutic regimens. 6 Furthermore, clinical data indicate that cyclophosphamide, especially in intermediate to higher dose levels, is effective in melphalan-resistant disease. 7,8 We have therefore conducted a phase II trial evaluating the safety and efficacy of non-infusional vincristine and epirubicin in addition to cyclophosphamide and high-dose dexamethasone as induction and salvage treatment in multiple myeloma.…”

Section: Introductionmentioning

confidence: 99%

Bolus vincristine and epirubicin with cyclophosphamide and dexamethasone (VECD) as induction and salvage treatment in multiple myeloma

et al. 1998

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The VAD regimen (infusional vincristine, doxorubicin and intermittent high-dose dexamethasone) is widely considered the standard salvage chemotherapy for multiple myeloma resistant to alkylating agents and is increasingly used for induction in previously untreated patients prior to high-dose chemotherapy. We investigated the VECD protocol, a VAD-based regimen using bolus injections of vincristine 1.5 mg day 1 and epirubicin 20 mg/m 2 days 2 and 3 with 1 h infusions of cyclophosphamide 200 mg/m 2 days 1-3 and oral dexamethasone 20 mg/m 2 days 1-5 as induction and salvage treatment in multiple myeloma. Fifteen previously untreated and 25 patients with relapsed or refractory myeloma were included. Cycles were repeated every 3 weeks. In the group of previously untreated patients the response rate was 53% and the median survival has not been reached at 59 months. For relapsed and refractory patients the response rate was 44% and the median survival 13 months. In the group of patients with truly refractory disease on prior chemotherapy a response rate of 47% was achieved, which appears superior to the results observed for VAD alone. The main toxicities were leukocytopenia WHO grade IV and infections grade III/IV with both toxicities being significantly more pronounced in pretreated patients. VECD appears to be an effective regimen for induction and salvage therapy in multiple myeloma. Based on the limited number of patients treated the results are comparable to those reported for VAD, with the advantage that the infusional application of vincristine and the anthracycline is omitted.

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Section: Introductionmentioning

confidence: 99%

Bolus vincristine and epirubicin with cyclophosphamide and dexamethasone (VECD) as induction and salvage treatment in multiple myeloma

et al. 1998

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“…Data from our laboratory have shown that a priming dose of cyclophosphamide given 7 d before high-dose melphalan (Maitland et al, 1990) or VAMP increased the clonogenecity of myeloma cells and subsequent cell kill. Thus cyclophosphamide was added to the regimen (C-VAMP) with the aim of activating tumour cells into cycle and therefore rendering them more susceptible to VAMP, although we also expected to obtain a direct effect on tumour cell kill from cyclophosphamide itself.…”

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confidence: 99%

A comparison of vincristine and doxorubicin infusional chemotherapy with methylprednisolone (VAMP) with the addition of weekly cyclophosphamide (C‐VAMP) as induction treatment followed by autografting in previously untreated myeloma

et al. 1997

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Summary. In a sequential nonrandomized study, 204 consecutive unselected patients aged < 70 years received induction chemotherapy with infusional vincristine and adriamycin with oral methyl prednisolone (VAMP; n ¼ 75) or with additional cyclophosphamide, C-VAMP (n ¼ 129). 38/129 C-VAMP patients also received verapamil during induction as part of a controlled trial with the aim to overcome drug resistance. A median of five courses (range 1-11) of chemotherapy were required before maximal response was attained and this was similar in both groups. An over-all response rate of 71% was noted at the end of induction. The complete remission (CR) rate with C-VAMP was 24%, which was significantly higher ( P ¼ 0 . 04) than the CR rate with VAMP alone (8%). The addition of verapamil did not alter the response rate of C-VAMP. Compliance to VAMP was overall 83% and not affected by the addition of cyclophosphamide. The proportion of patients going on to receive high-dose chemotherapy and an autograft was the same for VAMP and C-VAMP treated patients (71%). The median overall survival (OS) and progression-free survival (PFS) for the whole group were 4·4 years and 2·0 years and no difference in outcome was observed between the different treatment groups. Therefore the addition of weekly cyclophosphamide to VAMP induction therapy has significantly improved the response rates of previously untreated myeloma patients. C-VAMP was not more toxic and did not compromise the chances of receiving an autograft. Verapamil was without influence on any parameters in this study.

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“…Over the past two to three years we have investigated, in multiple myeloma patients, the relationship between types of clinical treatment and the growth of clonogenic myeloma cells (MY-CFUJ from bone marrow aspirates using an in vitro assay (Millar et af., 1988(Millar et af., , 1989Bell et af., 1988;Maitland et al, 1990). The first study involved patients receiving the drug combination vincristine, adriamycin and methyl prednisolone (VAMP) repeated every 21 days to maximum response followed by high dose melphalan at 140 mg/m2 or 200 mg/m2 with autologous bone marrow transplantation (Gore et af., 1989).…”

Section: Introductionmentioning

confidence: 99%

“…Data from our laboratory have shown that a 'priming' dose of cyclophosphamide (Millar and McElwain, 1978) (500 mg i.v. bolus) which is given to patients 7 days before high dose melphalan increases the clonogenicity of myeloma cells in vitro in approximately 68 per cent of patients (Maitland et al, 1990). The rationale for adding cyclophosphamide on days 1, 8 and 15 of the treatment was that activation of tumour cells into cycle might render them more susceptible to the toxic effects of VAMP as well as cyclophosphamide itself.…”

Section: Introductionmentioning

confidence: 99%

Decrease in clonogenic tumour cells in bone marrow aspirates from multiple myeloma patients due to the incorporation of cyclophosphamide into treatment with vincristine, adriamycin and methyl prednisolone

Bell

Millar

Montes-Borinaga

et al. 1990

Hematological Oncology

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A study of 32 patients receiving cyclophosphamide (CY) and verapamil (VER) in addition to the drug combination vincristine, adriamycin and methyl prednisolone (VAMP) was made in which the clinical response and growth of clonogenic myeloma cells (MY-CFUc) from bone marrow aspirates were compared. At presentation, MY-CFUc were grown from 72 per cent (23/32) of the patients. After treatment with CY-VAMP or VERCY-VAMP, MY-CFUc were grown from 25 per cent (8/32) of patients of whom only 50 per cent responded clinically. The overall clinical response rate for patients receiving CY-VAMP and VERCY-VAMP was 64 per cent (9/14) and 72 per cent (13/18) respectively of whom 14 per cent in each group achieved complete remission. There was no concomitant increase in normal tissue toxicity as measured by granulocyte-macrophage colony (GM-CFUc) formation. Comparison of these data with our previous study of patients receiving VAMP alone, suggests that the addition of CY to the regimen may increase the tumour cell kill. Further clinical studies will determine whether there is a significant increase in the complete remission rate.

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Evidence that multiple myeloma may be regulated by homeostatic control mechanisms: correlation of changes in the number of clonogenic myeloma cells in vitro with clinical response

Cited by 10 publications

References 12 publications

Bolus vincristine and epirubicin with cyclophosphamide and dexamethasone (VECD) as induction and salvage treatment in multiple myeloma

Bolus vincristine and epirubicin with cyclophosphamide and dexamethasone (VECD) as induction and salvage treatment in multiple myeloma

A comparison of vincristine and doxorubicin infusional chemotherapy with methylprednisolone (VAMP) with the addition of weekly cyclophosphamide (C‐VAMP) as induction treatment followed by autografting in previously untreated myeloma

Decrease in clonogenic tumour cells in bone marrow aspirates from multiple myeloma patients due to the incorporation of cyclophosphamide into treatment with vincristine, adriamycin and methyl prednisolone

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