Two epipodophyllotoxin derivatives, VM 26 and VP 16213, in the treatment of leukemias, hematosarcomas, and lymphomas

Mathé, G; Schwarzenberg, L; Pouillart, P; Oldham, Robert K.; Weiner, Roy S.; Jasmin, C; Rosenfeld, C.; Hayat, M.; Misset, Jean-Louis; Musset, M; Schneider, M.; Amiel, J. L.; Vassal, F. de

doi:10.1002/1097-0142(197410)34:4<985::aid-cncr2820340402>3.0.co;2-u

Cited by 111 publications

(12 citation statements)

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“…According to these observations, the effects of VP-16 on the cell cycle would be more intense in THP-1 than HL-60 cells. These results are compatible with the finding that VP-16 is more effective for patients with monocytic leukemia than for those with other types of leukemia (Mathe et al 1974;Bernasconi et al 1982;Varini and Cavalli 1982;Odom and Gordon 1984;Moriyama et al 1985). The present in vitro data would support the efficacy of VP-16 for treating monocytic leukemia in vivo.…”

Section: Resultsmentioning

confidence: 99%

“…These results suggest that the effects of VP-16 on the cell cycle may be more intense in THP-1 than HL-60 cells, and support the efficacy of VP-16 for treating monocytic leukemia in vivo. flow cytometry; cell cycle; bromodeoxyuridine (BrdU); etoposide (VP-16); cytosine arabinoside (Ara-C) Etoposide (VP-16), a newly developed semisynthetic derivative of podophyllotoxin (Loike and Horwitz 1976;Roberts et al 1980), is recently available for the treatment of acute leukemias and malignant lymphomas, and has been found useful for relapsed or refractory cases (Mathe et al 1974;Bishop et al 1990). This drug is considered more effective for patients with monocytic leukemia than for those with other types of leukemia (Mathe et al 1974;Bernasconi et al 1982; …”

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confidence: 99%

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Flow Cytometric Analysis of the Cell Cycle of the Leukemic Cell Lines Treated with Etoposide and Cytosine Arabinoside.

Ishiyama

Satoh

Igarashi

et al. 1994

Tohoku J. Exp. Med.

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(2), 95-107 Effects of etoposide (VP-16) and cytosine arabinoside (Ara-C) on the cell cycle of HL-60 and THP-1 cells were studied by flow cytometry using the bromodeoxyuridine (BrdU)/DNA assay technique to investigate the efficacy of VP-16 for monocytic leukemia cells. VP-16 inhibited the proliferation of THP-1 cells more strongly than that of HL-60 cells at any concentrations used at 24 and 48 hr. VP-16 arrested HL-60 and THP-1 cells in the G2 /M phase and reduced them in the Go/G1 and early S phase at higher concentrations. There was no significant difference in the percentage of G2/M phase cells at the same concentration between both cells. However, reduction in the Go/G, and early S phase cells was more marked in THP-1 than HL-60 cells significantly. On the other hand, Ara-C perturbed the cell cycle of HL-60 cells more than that of THP-1 cells at 24 and 48 hr. These results suggest that the effects of VP-16 on the cell cycle may be more intense in THP-1 than HL-60 cells, and support the efficacy of VP-16 for treating monocytic leukemia in vivo. flow cytometry; cell cycle; bromodeoxyuridine (BrdU); etoposide (VP-16); cytosine arabinoside (Ara-C) Etoposide (VP-16), a newly developed semisynthetic derivative of podophyllotoxin (Loike and Horwitz 1976;Roberts et al. 1980), is recently available for the treatment of acute leukemias and malignant lymphomas, and has been found useful for relapsed or refractory cases (Mathe et al. 1974;Bishop et al. 1990). This drug is considered more effective for patients with monocytic leukemia than for those with other types of leukemia (Mathe et al. 1974;Bernasconi et al. 1982;

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Flow Cytometric Analysis of the Cell Cycle of the Leukemic Cell Lines Treated with Etoposide and Cytosine Arabinoside.

Ishiyama

Satoh

Igarashi

et al. 1994

Tohoku J. Exp. Med.

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“…This combination was choosen based on the hypothesis that etoposide might have an additional antileukemic effect. [11][12][13] It shows high antineoplastic activity against a wide range of malignancies and a steep dose response with low extramedullary toxicity at standard dose.…”

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confidence: 99%

Dose-dependent effect of etoposide in combination with busulfan plus cyclophosphamide as conditioning for stem cell transplantation in patients with acute myeloid leukemia

Kröger

Zabelina

Sonnenberg

et al. 2000

Bone Marrow Transplant

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Summary:To evaluate the efficacy and toxicity of two different etoposide (VP-16) dosages (30 or 45 mg/kg) in combination with busulfan/cyclophosphamide as conditioning therapy followed by stem cell transplantation in acute myeloid leukemia (AML), 90 patients with AML received either 30 mg/kg (n = 60) or 45 mg/kg (n = 30) etoposide in combination with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). The stem cell source was allogeneic related bone marrow (BM) (n = 53), allogeneic unrelated BM (n = 5), allogeneic unrelated peripheral blood (PBSC) (n = 2), syngeneic BM (n = 2), autologous BM purged (n = 9) or unpurged (n = 9), autologous PBSC (n = 10). Fifty-six patients (62%) were in first CR, 26 (29%) were Ͼ first CR, and eight (9%) were transplanted in relapse. Principal toxicities in both groups were mucositis and hepatotoxicity. Forty-five mg/kg etoposide resulted in greater hepatic toxicity (P = 0.03), and a higher incidence of VOD (23 vs 12%, P = 0.04) and acute GVHD grade III/IV (13 vs 5%, NS). The treatment-related mortality was 17% in the 30 mg/kg group and 33% in the 45 mg/kg group, mainly due to infections, intestinal pneumonia and GVHD. Hematological recovery of leukocytes 1/nl was comparable in both groups (17 vs 16 days). After a median follow-up of 16 months 19% in the 30 mg/kg group and 23% in the 45 mg/kg group relapsed. In patients who had undergone allogeneic related bone marrow transplantation in first CR no relapses occurred after a median follow-up of 3 years. For all patients the 3-year estimated disease-free survival was 62% in the 30 mg/kg group and 40% in the 45 mg/kg group (P = 0.03). For patients in first CR who underwent allogeneic related stem cell transplantation the 3 year disease-free survivals were 80% and 66%, respectively (P = 0.4). We conclude that etoposide 30 mg/kg or 45 mg/kg in combination with busulfan/cyclophosphamide is a highly active regimen 1-3 The use of allogeneic or autologous bone marrow transplantation increases the rate of long-term survival, although a substantial number of patients still relapse. 4,5 The relapse rate after autologous transplantation in first CR is about 50% and after allogeneic transplantation about 20%. 6 It is possible that improved preparative regimens will reduce these relapse rates. The most common preparative regimens in acute myeloid leukemia are busulfan and cyclophosphamide or TBI plus cyclophosphamide. 7,8 It has already been shown that an intensified preparative regimen can lower the relapse rate in allogeneic as well as in autologous transplantation. 5,9,10 We incorporated etoposide 45 or 30 mg/kg to a conditioning regimen consisting of busulfan (16 mg/kg) plus cyclophosphamide (120 mg/kg) to investigate the efficacy and toxicity of this new preparative regimen in patients with acute myeloid leukemia undergoing autologous or allogeneic stem cell transplantation. This combination was choosen based on the hypothesis that etoposide might have an additional antileukemic effect.11-13 It shows high antineoplastic activity against a ...

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“…The therapeutic potential of a new class of anticancer drugs-the epipodophyllotoxins [ 1,2]-is evident from clinical trials with advanced acute leukemias and certain malignant solid tumors [3,4]. VP16-213 is now considered among the most active available compounds for treatment of small cell carcinoma of the lung [5] and acute monocytic leukemia [6]. VM-26, administered either in combination or as a single agent, is effective against late stages of the lymphocytic leukemias, lymphomas, and childhood neuroblastoma [7-lo].…”

Section: Introductionmentioning

confidence: 99%

Vm‐26 with prednisone and vincristine for treatment of refractory acute lymphocytic leukemia

Rivera

Bowman

Murphy

et al. 1982

Med. Pediatr. Oncol.

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Fifty-six children with refractory acute lymphocytic leukemia (ALL) were assessed for remission-induction responses to VM-26 (250 mg/m2 per week) in combination with prednisone (40 mg/m2 per day) and vincristine (1.5 mg/m2 per week). Each child had been treated intensively with steroids, vincristine, daunorubicin and L-asparaginase. In fact, all patients had failed to respond to previous reinduction therapy with prednisone-vincristine or had relapsed while receiving vincristine. Our intent in this study was to test whether or not addition of VM-26 to prednisone-vincristine would overcome clinical resistance to these established agents. Complete remissions were induced in 17 patients (0.30) over 4 to 6 weeks. Five of these children, all clinically unresponsive to prednisone-vincristine alone, had complete remissions that lasted longer than 1 year; two remain in remission for 2 1/2 years and both are now off therapy. Myelosuppression, the most serious treatment complication, was documented in 20 of 26 evaluable patients. The median time to recovery of normal marrow function was 15 days. These results demonstrate further the potential of VM-26 in combined-drug treatment of refractory ALL. Whether the effectiveness of this combination represents potentiation of prednisone and vincristine activity by VM-26 or some other, as yet unidentified interaction, remains to be determined.

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Two epipodophyllotoxin derivatives, VM 26 and VP 16213, in the treatment of leukemias, hematosarcomas, and lymphomas

Cited by 111 publications

References 5 publications

Flow Cytometric Analysis of the Cell Cycle of the Leukemic Cell Lines Treated with Etoposide and Cytosine Arabinoside.

Flow Cytometric Analysis of the Cell Cycle of the Leukemic Cell Lines Treated with Etoposide and Cytosine Arabinoside.

Dose-dependent effect of etoposide in combination with busulfan plus cyclophosphamide as conditioning for stem cell transplantation in patients with acute myeloid leukemia

Vm‐26 with prednisone and vincristine for treatment of refractory acute lymphocytic leukemia

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