Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-five patients with advanced non-small-cell lung carcinoma (NSCLC) were treated with a multidrug regimen (CIV) consisting of ifosfamide (IFX), cisplatin (CDDP), and etoposide (VP-16). Twenty-four patients were evaluable for response. An objective response was detected in eight cases (33%), including one case with complete tumor response. Median duration of response was 31 weeks, and median overall survival 46 weeks, with no significant difference between responders and nonresponders. Myelosuppression and gastrointestinal side effects represented the main toxic manifestations; a toxic death and an ischemic cardiac episode were also observed. CIV seems a moderately effective regimen in NSCLC, but unlikely to provide an advantage over the widely employed two-drug combination of CDDP and VP-16.
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PMID:Pilot study with cisplatin, ifosfamide, and etoposide in advanced non-small-cell lung carcinoma. 217 19

Etoposide and teniposide are semi-synthetic glucoside derivatives of podophyllotoxin with a documented anti-tumour activity in various types of malignant diseases. It was an early observation that these epiphodophyllotoxins were efficacious in hematological malignancies such as lymphomas and leukemias. In this report the clinical evidence supporting the activity of etoposide and teniposide in acute lymphoblastic (ALL) and non-lymphoblastic leukemia (ANLL) is reviewed. Unlike podophyllotoxin, etoposide and teniposide do not appear to affect microtubular function nor arrest cells in mitosis. These epiphodophyllotoxins, like other DNA intercalating agents, have topoisomerase II as their target. Most studies with etoposide have been performed in ANLL and with teniposide in ALL. This choice seems to be rather arbitrary and is better explained by traditional reasons than actual study results. The data in acute leukemias are partly flawed by the absence of certain prospective comparative trials. However, the current information on etoposide clearly shows that this agent has substantial activity in ANLL and may well be incorporated into front-line regimens and the same is true for teniposide in the treatment of ALL. Nevertheless, based on available literature, there are no convincing data to the author's mind to support that one of these agents is superior to the other in the treatment of acute leukemias.
Med Oncol Tumor Pharmacother 1990
PMID:Etoposide and teniposide in the treatment of acute leukemia. 218 20

Four cases of B cell lymphoma, seen at the Department of Dermatology, Miyazaki Medical College, for the previous approximately 10 years, were reviewed. Case 1 was characterized by a localized tumours lesion on the head; the histologic picture was of the follicular, medium sized cell type. Complete remission for 8 years has been obtained after electron beam therapy and surgical removal of the tumor. Cases 2 and 3 had a histologic picture of diffuse, large cell type and were assumed to have a bad prognosis with standard chemotherapy. In addition to conventional chemotherapy, they were placed on noncross-resistant alternating combination chemotherapy with medium dosages of MTX, VP-16, VDS, PCZ MXT, PEP and ACR, so as not to develop cross resistance. Case 2 has been in complete remission for 11 months and case 3 for 7 months. Case 4 was a nodal lymphoma with skin lesions. This patient was treated mainly by local radiation therapy, but later died with leukemic changes and renal failure. Cutaneous B cell lymphoma should be treated vigorously and carefully, since it has a poorer prognosis than that of lymphoma of lymph node origin.
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PMID:[Treatment of four cases of B-cell lymphoma]. 219 Nov 58

Ten previously untreated patients with gastric cancer were treated with etoposide, 120 mg/m2 intravenously (i.v.) on days 4, 5, and 6, Adriamycin, 20 mg/m2 i.v. on days 1 and 7, and cisplatin, 40 mg/m2 i.v. on days 2 and 8 (EAP). Etoposide, 240 mg/m2 on days 4, 5, and 6, was administered orally instead of intravenously in alternating cycles, and pharmacokinetic studies were performed in those who had previously undergone gastrectomy or who had tumor infiltrating the stomach to determine oral bioavailability. Nine patients had advanced measurable gastric cancer, and one patient had an elevated carcinoembryonic antigen after surgery for synchronous gastric and colon cancer. The median age was 54 years (range 38-69), and the median Eastern Cooperative Oncology Group (ECOG) performance status was 2 (range 0-3). Nine of 10 patients had poorly differentiated adenocarcinoma. Twenty-four cycles were administered to 10 patients, and hematologic data were available for 23 courses. ECOG grade 4 neutropenia and thrombocytopenia developed in 19 (83%) and 8 (53%) courses, respectively. Thirteen courses (54%) were complicated by fever requiring parenteral antibiotics. Two patients (20%) died due to neutropenic sepsis. The profound myelotoxicity observed in our study prompted us to terminate the investigation prior to completing accrual. The oral bioavailability of etoposide was 21% and 36% in the two patients who had had prior gastrectomy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase II trial of etoposide, doxorubicin (Adriamycin), and cisplatin (EAP regimen) in advanced gastric cancer. 222 Jun 57

We studied the effects of two modulators of multidrug resistance (MDR), cyclosporine and verapamil, on the cytotoxicity of etoposide (VP-16) in normal human bone marrow; two human leukemia cell lines, K562 and CEM; their MDR variants, K562/DOX and CEM/VLB; and mixtures of normal marrow and leukemic cells. VP-16 was selectivity toxic to the parental leukemic cells, with IC-50 values of 2 microM for CEM cells, 1.5 microM for K562 cells, and 12 microM for normal marrow CFU-GM. This selectivity was lost in the MDR variant leukemia cells, with IC-50s of 20 microM in K562/DOX and 8 microMs in CEM/VLB. Cyclosporine, 6 microMs, and verapamil, 20 microM, alone were nontoxic to bone marrow CFU-GM, and did not significantly increase the toxicity of VP-16 to normal marrow cells or to the two drug-sensitive leukemic cell lines. However, cyclosporine specifically enhanced the cytotoxicity of VP-16 in the MDR leukemia cells, reducing the IC-50 to the same level as the parental sensitive cells. Verapamil was considerably less effective. In a mixing experiment that included K562/DOX cells and normal bone marrow, cyclosporine increased the toxicity of VP-16 to the resistant leukemic cells by nearly 20-fold. Because the cytotoxic effect of cyclosporine is additive for resistant tumor cells, its combination with VP-16 may be useful in the purging of contaminating tumor cells prior to autologous bone marrow transplantation.
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PMID:Modulation of etoposide (VP-16) cytotoxicity by verapamil or cyclosporine in multidrug-resistant human leukemic cell lines and normal bone marrow. 222 79

Induction of transient thermotolerance by heat or other cytotoxic stressors has been reported to confer a moderate degree of drug resistance to tumor cells in vitro. In this study, a genetically stable, heat-resistant mouse B16 melanoma variant (W-H75) was tested for its sensitivity to various cytotoxic and antiproliferative agents. The heat-resistant W-H75 cells displayed a moderate two- to threefold resistance to doxorubicin, VP-16, VM-26, colchicine, cis-dichlorodiammineplatinum(II), HgCl2, and CdCl2. Marginal resistance to 4'(9-acridinylamino)methanesulfon-m-anisidide vinblastine, 1,3-bis(2-chloroethyl)-1-nitro-sourea, and NaAsO2 was observed, while no difference in sensitivity to the anticancer drugs, actinomycin D and camptothecin, was observed. Although W-H75 cells were generally more resistant than the parental cells to most of the agents that were tested, they were collaterally sensitive to the antimetabolites methotrexate and 6-mercaptopurine. Resistance of the W-H75 cells to epipodophyllotoxins and anthracyclines was not due to differences in steady-state drug accumulation. For the epipodophyllotoxin VP-16, resistance may be related to a relative decrease in the number of drug-induced DNA strand breaks in W-H75 cells. However, no difference in DNA strand breakage was observed between W-H75 and parental cells which were treated with doxorubicin, suggesting that resistance to this drug occurred by a different mechanism. The possible involvement of glutathione and glutathione S-transferase in resistance was also investigated. The glutathione content in W-H75 cells was 35% higher than that in the parental line. However, glutathione S-transferase activity appeared to be identical in both cell lines. Two other heat-resistant B16 melanoma variants, B-H103 and R-H92, were also tested for sensitivity to doxorubicin and VP-16. In contrast to the W-H75 cells, these two heat-resistant variants were hypersensitive to doxorubicin. The B-H103 cells were also hypersensitive to VP-16. This study suggests that selection for cellular resistance to heat may result in cells that have an altered sensitivity to drugs.
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PMID:Drug sensitivity of heat-resistant mouse B16 melanoma variants. 223 92

The West Japan Pediatric Oncology Group studied the treatment of pediatric malignant tumors with VP-16 from December 1984 to March 1988. Study subjects were divided into two groups. One group received only VP-16, while the other received VP-16 combined with other anti-tumor agents. VP-16 evaluation was possible in a total of 116 cases. The efficacy rate was calculated by considering both complete and partial remission as effective. The efficacy rate for VP-16 alone was 87.5% for primary cases of ANLL and 100% for primary cases of histiocytosis. The efficacy rates for combination therapy were as follows: 92.6% for primary cases of ANLL, 66.7% for primary cases of histiocytosis, 45.5% for relapsed cases of ANLL and 66.7% for relapsed cases of ALL. Bone marrow suppression was seen in the form of leukopenia and thrombocytopenia for 2 to 3 weeks after VP-16 administration. Alopecia, mucositis and gastrointestinal symptoms were also observed, but they presented no significant problem. From our results, we believe that chemotherapy including VP-16 is effective for remission induction therapy in primary cases of ANLL and for salvage therapy in relapsed leukemia. Additionally, VP-16 is considered to be effective for the treatment of histiocytosis.
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PMID:Treatment of pediatric malignant tumors with VP-16. West Japan Pediatric Oncology Group. 223 3

A 71-year-old male underwent therapeutic pneumothorax for left pulmonary tuberculosis 42 years ago. He visited our hospital in February 1988 with a complaint of hemosputum. In October, cytology of sputum revealed malignant cells, and the patient was admitted to our hospital for further examination. Because malignant cells were found by the left bronchial lavage, pan-pleuropneumonectomy was performed on January 12, 1989 under the diagnosis of left lung cancer. The tumor was partially left unremoved. Histological diagnosis was diffuse large cell type, B cell non-Hodgkin's lymphoma. Postoperatively, 2 courses of cyclophosphamide, adriamycin, vincristine, prednisone, etoposide (CHOP and VP-16) therapy were performed. However, the patient died of respiratory insufficiency on the 125th postoperative day. Recently, cases of malignant lymphoma involving the pleura after the old tuberculous empyema and therapeutic pneumothorax have been increased. Therefore, prompt diagnosis and treatment are recommended when tumor shadow is suspected as a result of imaging examination.
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PMID:[Non-Hodgkin's lymphoma arising from the wall of old tuberculous empyema--a surgical case report]. 224 44

CDDP, MMC, UFT and Etoposide (PMUE)-combined therapy was applied to 60 cases of terminal gastric cancer to examine its effectiveness. PMUE therapy consists of i.v. injection of CDDP 75 mg/body and MMC 10 mg/body on day 1, i.v. injection of Etoposide 50 mg/body on days 3, 4 and 5 and consecutive daily administration of UFT 400 mg/body, with 3 weeks as one course. Of 42 cases having estimable lesions, 23 (53.8%) showed high rate of effectiveness (PR). Especially, of 23 cases receiving no previous treatment, 15 (65.2%) benefitted by the therapy (PR) and 9 (69.2%) of 13 non-resected cases, to a wonderful extent. Five non-resected cases showed such a reduction in tumor size as made gastrectomy possible. As for the prognosis, one year-survival rate was 34.3, 49.0 and 16.0% for all 42 cases, 23 effective cases and 19 ineffective cases, respectively, with significant (p less than 0.001) prognostic prolongation for effective cases compared with ineffective ones. Side effects were digestive symptoms (85.7%), epilation (81.0%) and myelopathy (73.8%), which were all transitory and recovered. The present PMUE therapy was regarded as one of the best combined chemotherapies for terminal gastric cancer.
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PMID:[Effect of PMUE therapy (CDDP, MMC, UFT, etoposide) in terminal gastric cancer]. 226 Aug 75

The comet assay, which measures DNA strand breakage in individual cells, was used to examine the relation between DNA damage, cell survival, and resistance to the topoisomerase II inhibitor etoposide (VP-16). Chinese hamster V79-171b cells and a VP-16-resistant subline (VPr) were exposed to VP-16 as monolayers or spheroids. The comet assay was comparable in sensitivity to the DNA precipitation and alkali unwinding assays for detecting DNA strand breaks induced by VP-16. However, unlike conventional DNA damage assays, the comet assay also indicated heterogeneity in cell response. For V79 multicell spheroids exposed to VP-16, the external cycling cells were 50 times more sensitive to killing and DNA damage than the internal noncycling cells; the comet assay indicated the fraction of cells resistant to the drug. VPr cells, which were 10 times more resistant to killing and DNA damage by VP-16 than the parent cell line, could also be identified in mixed populations with the use of this method. These results suggest that the comet assay could be useful in predicting tumor cell response to DNA-damaging agents.
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PMID:Detection of etoposide resistance by measuring DNA damage in individual Chinese hamster cells. 232 48


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