Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High-dose etoposide has been added to total body irradiation, cyclophosphamide, carmustine, or busulfan in preparatory regimens for allogeneic or autologous bone marrow transplantation for patients with leukemia, Hodgkin's disease, lymphoma, or multiple myeloma. The treatment results are encouraging, indicating that etoposide may be a valuable addition to the previously established regimens. Etoposide should be incorporated into collaborative, prospective trials to define its ultimate role in bone marrow transplantation.
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PMID:High-dose etoposide (VP-16)-containing preparatory regimens in allogeneic and autologous bone marrow transplantation for hematologic malignancies. 149 28

Eleven patients with advanced multiple myeloma refractory to standard doses of alkylating agents and salvage therapy with vincristine, adriamycin and dexamethasone (VAD) were treated with high dose cyclophosphamide, BCNU and VP-16 (CBV) with autologous blood stem cell support. Seven patients had marked marrow plasmacytosis (greater than 30%) and four had extensive pelvic bone disease precluding autologous marrow harvest. Four patients responded with a median remission duration of 7 months. Recovery of granulocytes and platelets occurred promptly in 10 evaluable patients with complete hematologic recovery. Autologous blood stem cells can provide safe and effective support for high dose CBV treatment of myeloma patients with extensive marrow plasmacytosis. The short remissions call for better cytoreductive regimens with consideration for earlier use when the myeloma may be more responsive to therapy.
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PMID:High dose cyclophosphamide, BCNU and VP-16 with autologous blood stem cell support for refractory multiple myeloma. 197 Sep 39

A patient with plasma cell myeloma refractory to both MP (melphalan-prednisolone) and VAD (vincristine-adriamycin-dexamethasone) was treated with a combination chemotherapy consisting of VP-16, ifosfamide and dexamethasone (VID). A partial remission of 12-month duration was achieved. VID combination might be considered for myeloma patients who are refractory to both MP and VAD, and not eligible for high-dose melphalan with bone marrow transplantation.
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PMID:Etoposide and ifosfamide for MP (melphalan and prednisolone)- and VAD (vincristine, adriamycin and dexamethasone)-resistant plasma cell myeloma: a case report. 208 76

A retrospective analysis was made of elderly cancer patients (pts) who were treated with cancer chemotherapy in our Department of the Cancer Inst. Hosp. There were 180 pts above age 70 years at the start of chemotherapy between July of 1974 and December of 1988. Characteristics of these 180 pts were as follows: (1) 73 years of age in median (70-89 years), (2) 67 pts with malignant lymphoma (37%); 40 with lung ca. (22%), 20 with breast ca. (11%), stomach ca., colorectal ca., multiple myeloma and other; (3) Combination chemotherapy given to 174 pts; (4) OUTCOME: 41 pts (23%) were alive as September of 1989, and autopsy performed in 66 out of 87 pts who died in the hospital (76%). There were no special chemotherapeutic regimens only for elderly pts. Intensity of adequate chemotherapy based on therapeutic protocols was evaluated, dividing pts into two groups: full-dose group and reduced-dose group. Most pts (96%) with small cell lung cancer (SCL) were treated on protocols. For example, 12 elderly pts with SCL were treated with VEC regimen (VCR.VP-16.CTX); eight pts with full-dose and four reduced-dose, and their response rate (CR/PR) of 50%/38% and 25%/75%, respectively, and in 23 younger pts; 20 full-dose and three reduced-dose, and response rate 35%/35% and 33%/33%, respectively. There were 40 pts with acute non-lymphocytic leukemia over 60 years old, treated at Jikei University and in our Department. CR rates of these pts according to age showed a lower percentage with advancing age. Elderly pts with malignancies responsive to chemotherapy should be treated with the same regimen used in younger pts. But doses of each drug have to be adjusted to organ functions of each pt. patients with unresponsive malignancies, must be enrolled in clinical trials, and their responses and toxicities evaluated by age-stratified analysis.
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PMID:[Treatment of cancer in the elderly--cancer chemotherapy]. 216 Jul 99

This report summarizes a broad experience in the treatment of patients with multiple myeloma resistant to standard chemotherapy. The VAD regimen has induced remissions in about 50% of relapsing patients but in only about 25% of previously unresponsive patients. In patients resistant to VAD, high-dose therapies with intravenous melphalan, a CBV combination (cyclophosphamide-BCNU-VP-16) or an EDAP regimen (VP-16 -platinum) produced responses in about 40% of patients. However, these treatments usually required autologous bone marrow or blood stem cell support and the median duration of control was only 6 months. With an even more intensive program using high-dose melphalan and total body irradiation supported by autologous bone marrow, all patients who survived the early treatment period responded for a median duration of about 1 year. Results indicated a dose-response effect of chemoradiotherapy on VAD-resistant myeloma with the potential that such intensive regimens will prolong disease-free survival time.
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PMID:Chemotherapy for resistant and relapsing multiple myeloma. 257 5

To assess the usefulness of 4-hydroperoxycyclophosphamide (4-HC) and Etoposide (VP-16) as a purging agent for myeloma cells in bone marrow ex-vivo, myeloma cell lines (SK-RCS-1, RPMI-8226), lymphoma cell line (SK-DHL-2) and normal bone marrow (BM) cells were treated at different concentrations of 4-HC, VP-16. In separate experiments, LAK cells or antibodies were also used to treat the above cell lines. Clonogenic tumor cells from all three cell lines could be reduced by more than 4 logs, when treated alone or as a mixture with irradiated normal bone marrow cells at a 4-HC concentration of 60 mumol/l. Under similar conditions, approximately 1% of normal BM myeloid progenitor granulocyte-macrophage colony forming cells (CFU-GM) survived. The results with LAK cells and antibodies were also encouraging. These observations support the use of various purging methods for myeloma cells for autologous bone marrow transplantation.
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PMID:Ex vivo treatment of myeloma cells by 4-HC, VP-16, LAK cells and antibodies. 262 87

The anticancer agent etoposide (VP-16) produces DNA strand scission in intact tumor cells or isolated nuclei. This activity may be mediated by topoisomerase II, an enzyme capable of producing double strand breaks in mammalian cells. Two established tumor cell lines were examined to see whether polyamines, which alter DNA conformation and topoisomerase II activities, affected the cytotoxicity, strand scission, and antitumor efficacy of VP-16. L1210 murine leukemia and 8226 human myeloma cells were treated with alpha-difluoromethylornithine (DFMO) to reduce intracellular polyamine levels via inhibition of ornithine decarboxylase. The polyamines putrescine and spermidine were markedly reduced by a 48-h incubation with 50 microM DFMO. This DFMO concentration did not inhibit colony formation in either cell line, but did reduce the growth rate of both cultures. In contrast, VP-16 produced a dose-dependent inhibition of colony formation. This was especially marked in the 8226 cell line. This correlated with DNA single strand breaks (SSBs) detected by the alkaline elution technique. When cells previously treated with DFMO were exposed to VP-16, a synergistic inhibition of colony formation (determined by isobologram analysis) was observed. However, VP-16-induced SSBs were only marginally increased by the DFMO pretreatment. When putrescine was combined concurrently with VP-16, both the in vitro cytotoxic effects and the number of DNA SSBs in L1210 cells were significantly reduced. These results demonstrate that putrescine inhibits VP-16-induced SSBs and commensurate cytotoxic effects, while DFMO, which depletes intracellular putrescine and partially reduces intracellular spermidine, acts to produce synergistic cytotoxic effects when combined with VP-16.
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PMID:Modulation of etoposide cytotoxicity and DNA strand scission in L1210 and 8226 cells by polyamines. 301 79

Having reviewed conventional chemotherapy of acute leukaemia in the preceding article, a discussion of high dose chemotherapy in haematological malignancy is presented. The indications and side-effects of high dose methotrexate, ifosfamide and etoposide (VP-16) are summarized in tabular form. The toxicity and effectiveness of high dose cytosine arabinoside in the treatment of refractory acute leukaemia is discussed. The use of high dose melphalan to treat patients with multiple myeloma or other tumours is reviewed. The most widely used cytoreductive regimes in bone marrow transplantation, high dose busulphan, high dose cyclophosphamide and total body irradiation are described.
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PMID:Therapeutic progress--review XXVII. High dose chemotherapy in haematological malignancy. 330 28

Purified human leukocyte interferon produced by recombinant techniques (IFN-alpha A) was tested in vitro with chemotherapeutic drugs, vinblastine (VLB), vincristine (VCR), vindesine (VDS), vinzolidine (VZL), cis-platinum (PLAT), doxorubicin (DOXO), etoposide (VP-16), and melphalan (MEL). The activity of these agents alone or in combination was tested against various human tumor cell lines, using a modified soft agar clonogenic assay. Three human tumor cell lines (myeloma, RPMI 8226; breast, MCF-7; and colon, WiDR) showed sensitivity to these agents at clinically achievable drug concentrations. Statistically significant synergistic activity against in vitro colony formation was observed with the combination of VLB and IFN-alpha A. An additive or sub-additive effect was usually observed with the other agents tested. Continuous exposure of the 8226 myeloma cell line to both IFN-alpha A and PLAT showed evidence of a more significant potentiation. It is hypothesized that the synergistic effect observed between VLB and IFN-alpha A is due to some of their common mechanisms of action.
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PMID:Interactions of human leukocyte interferon with vinca alkaloids and other chemotherapeutic agents against human tumors in clonogenic assay. 686 Dec 60

Peripheral blood stem cells (PBSC) were collected from 24 patients who were treated with high dose etoposide. Studied patients included one with acute lymphoblastic leukemia, 4 with acute myeloid leukemia (AML), 1 with myelodysplastic syndrome, 13 with lymphoma, 1 with malignant histiocytosis, 2 with myeloma, and 4 with testicular tumor. Etoposide was infused at a dose of 500 mg/m2 for 4 days, followed by subcutaneous injection of recombinant human granulocyte-colony stimulating factor from the nadir of leukocyte. PBSC were collected by processing 15-20 liters of blood apheresis in the recovery phase of chemotherapy. In all patients, the number of CFU-GM collected per aphereresis ranged from 0.01 to 59.4 x 10(5)/kg, and more than 5 x 10(5)/kg CFU-GM were collected in 19 of the patients (73%). All leukemia patients treated along with our protocols have remained in complete remission, but one patient with AML relapsed within 1 month after the treatment. Ten lymphoma patients were assessable for antitumor effect, and complete response (CR) was observed in 2, partial response (PR) was 7, and no change (NC) in one patient. Two patients with myeloma were classified to be NC. Three of the 4 patients with testicular tumor were PR, and the other one was NC. Eleven patients subsequently underwent PBSCT. The number of days required to achieve an absolute granulocyte count of 0.5 x 10(9)/l was 7 to 11 days, with a mean of 8.6.
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PMID:[Peripheral blood stem cell collection with high dose etoposide]. 754 Feb 21


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