Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eight consecutive patients with recurrent malignant oligodendroglioma were treated with systemic chemotherapy. Six patients received a combination of procarbazine, lomustine (CCNU), and vincristine; 1 received carmustine (BCNU), and 1 diaziquone. All responded by clinical and computed tomographic scan criteria. One patient had a complete response for 78 weeks, and 7 patients had unequivocal partial responses lasting 30+ to 68+ weeks. Two partial responders had complete control of systemic metastases. Malignant oligodendroglioma is a uniquely chemosensitive glial tumor.
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PMID:Successful chemotherapy for recurrent malignant oligodendroglioma. 338 71

A multi-institutional cooperative study of patients with locally advanced, recurrent, or metastatic gastric adenocarcinoma who had not previously received chemotherapy was conducted, prospectively randomizing patients to receive either doxorubicin or the three-drug combination, 5-fluorouracil (5-FU), doxorubicin (Adriamycin; Adria Laboratories, Columbus, Ohio), and BCNU (FAB). The 187 evaluable patients were initially stratified according to the presence of measurable or evaluable disease and performance status. There was a significantly higher response rate observed for FAB (40%) compared with doxorubicin (13%) among the 145 measurable-disease patients. Duration of response and survival were significantly longer for FAB in the measurable-disease group, but for the total patient population an early advantage for FAB in time to disease progression and survival was lost with continued follow-up. Median survival was 33 weeks for patients receiving FAB and 19 weeks for those receiving doxorubicin. Significant pretreatment factors adversely affecting survival included poor performance status, weight loss of greater than 10%, and more than two sites of metastases. Toxicity was not severe in either treatment arm, and only thrombocytopenia occurred significantly more often with FAB. It is contended that in the treatment of advanced gastric cancer, chemotherapy only exerts a relatively short-term and modest beneficial effect, most apparent in patients with intermediate tumor bulk. 5-FU remains the most active single agent, and combination chemotherapy has not yet proven its overall worth. Further studies are indicated comparing the most active combinations with 5-FU using optimal doses and schedules, and consideration must be given to the incorporation of no-treatment controls.
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PMID:Analysis of a prospectively randomized comparison of doxorubicin versus 5-fluorouracil, doxorubicin, and BCNU in advanced gastric cancer: implications for future studies. 352 4

Seventeen patients with metastatic breast cancer were treated with a high-dose combination chemotherapy regimen and autologous bone marrow support. Thirteen patients had prior combination chemotherapy. Fifteen patients were treated with a phase II regimen of cyclophosphamide (5.625 g/m2), cisplatin (165 mg/m2), and BCNU (600 mg/m2). Bone marrow harvest and reconstitution were uncomplicated. All patients became profoundly myelosuppressed. Fourteen of 16 evaluable patients (88%) responded, including six complete responses (CRs) (38%). The median time to tumor progression was 5 months. The median survival was 8 months. CRs occurred more frequently in patients with no prior chemotherapy for metastatic disease, inflammatory breast cancer; and patients treated within 3 months of first recurrence. The rate of tumor regression was rapid, with a median of 11 days to partial response (PR) and 12 days to CR. Those patients achieving a PR by day 7 had a greater likelihood (P = .03) of attaining a CR than those patients whose PR occurred later. Three deaths (18%) occurred, all in women with inflammatory breast cancer treated with prior chemotherapy. High-dose combined alkylating agent therapy produced high PR and CR rates in metastatic breast cancer patients, most of whom had failed prior chemotherapy. The rate of tumor regression was rapid. Current efforts are directed at developing a regimen using drugs specifically active in breast cancer, with an intent of combining an effective high-dose regimen with additional modalities of therapy in the treatment of breast cancer.
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PMID:High-dose combination alkylating agent chemotherapy with autologous bone marrow support for metastatic breast cancer. 353 55

Between January 1982 and June 1985, 105 patients with brain metastases of malignant solid tumours were treated in the Robert Janker Clinic. In order to optimize the overall response rates, concomitant radiotherapy and cytostatic chemotherapy was used. In most cases the primary tumour was located in the breast or the lung. Radiotherapy was performed with a Cobalt 60 equipment. The whole brain was irradiated in daily fractions of 15 Gy up to total dose of 45 Gy. Using a slit-course technique this dose was distributed to the three cycles of chemotherapy and given simultaneously, i.e. 15 Gy/ by course. The chemotherapeutic regimen consisted of ifosfamide daily for five days at 2g/m2 and the nitrosurea derivative carmustin (BCNU) at 30 mg/m2 on days 1, 3 and 5. After a free interval of four to five weeks the concomitant radiotherapy and chemotherapy was repeated twice. The tolerance of the treatment was generally good; no severe haematological or gastrointestinal complications occurred. There was a complete and permanent alopecia in all patients caused by the radiation. All patients received a cranial computerized axial tomographic scan prior to and after the treatment. According to the criteria of the International Union Against Cancer, there was a complete remission in 26 of the 105 patients and a partial remission in 49; 19 patients showed a stable disease. Only 12 of the 105 treated patients had a progression of their metastases. Only patients with partial or complete remissions after the treatment belong to the "long-term" survivors.
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PMID:Simultaneous radiotherapy and chemotherapy in the treatment of brain metastases of malignant solid tumours. 366 11

Sarcomas of childhood rank fifth in incidence of malignant tumors in children younger than 15 years. Among the soft tissue sarcomas, approximately 50% are rhabdomyosarcomas. The remainder represent a heterogeneous group of diverse sarcomas which are not unique to children and include fibrosarcoma, synoviosarcoma, malignant fibrous histiocytoma, malignant schwannoma, angiosarcoma, leiomyosarcoma, and others. The most common bone cancers in childhood are osteosarcoma and Ewing's sarcoma. Although a multidisciplinary approach utilizing surgery, irradiation, and combination chemotherapy is routinely used in management of virtually all children with solid tumors, the value of adjuvant chemotherapy in select bone and rare soft tissue sarcomas is currently being tested. Multiagent chemotherapy including vincristine, dactinomycin, cyclophosphamide, and Adriamycin (doxorubicin) contribute to cure rates in 65% to 75% of children with localized rhabdomyosarcoma, Stages I to III, when combined with surgery and/or irradiation. Other drugs which hold promise include platinum, DTIC, methotrexate, and VP-16. The efficacy of similar drugs in the rarer pediatric soft tissue sarcomas other than rhabdomyosarcoma and its variants requires prospective randomized trials evaluating histologic grade, tumor size, and nodal status. It has been suggested that the high-grade sarcomas presenting with minimal tumor bulk are most sensitive to combined radiotherapy-chemotherapy, whereas the low-grade sarcomas are more resistant to such therapy. Tumor cell heterogeneity contributes to biologic diversity and response to treatment. Chemotherapy as adjuvant therapy to irradiation is currently recommended and utilized for Ewing's sarcoma with survival rates approaching 80%, and disease-free survival of approximately 75% for those with localized disease. Children with widespread and metastatic disease at presentation fare less well. Although multiple single agents exhibit response rates ranging from 40% to 60%, including cyclophosphamide, Adriamycin, dactinomycin, BCNU, mithramycin, and 5-fluorouracil, new and more effective agents are needed. Controversy regarding the value of multiagent chemotherapy in osteosarcoma has stimulated prospective randomized trials. Evaluation of local control rates as well as sites and occurrence of metastases are essential in assessing the contribution of aggressive combined modality therapy in the pediatric sarcomas. Emphasis on refinement of therapy in determining the risk/benefit ratio from adjuvant chemotherapy in pediatric sarcomas is mandatory. Enhancement of early local reactions is apparent when adjuvant chemotherapy is used with local radiotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The value of adjuvant chemotherapy in the management of sarcomas in children. 388 37

The ability of the in vitro sister chromatid exchange (SCE) assay to predict in vivo tumor drug sensitivity was investigated using a spontaneous hepatocarcinoma in C3Hf/Kam mice and 3 chemotherapeutic agents: melphalan; cis-platinum; and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). For hepatocarcinoma cells grown in monolayer culture, melphalan was the most efficient at inducing SCEs, and BCNU, the least. cis-Platinum induced a range in SCEs that overlapped those of BCNU and melphalan, suggesting that hepatocarcinoma is not a homogeneous population with intermediate sensitivity, but is a mixture of cis-platinum-sensitive and -resistant cells. According to in vitro cell survival curves, hepatocarcinoma was most sensitive to melphalan, less sensitive to cis-platinum, and essentially resistant to BCNU. The relative antineoplastic effects of melphalan, cis-platinum, and BCNU in vivo were compared by the response of artificial and spontaneous pulmonary metastases and solid tumors to these agents. For artificial metastases, there was a dose-dependent decrease in the number of lung nodules in mice treated with melphalan or cis-platinum, with melphalan being the more effective. BCNU had no effect. Spontaneous pulmonary metastases generated from hepatocarcinoma leg tumors were reduced in those mice treated with melphalan, unaffected by cis-platinum, and increased by BCNU. In hepatocarcinoma leg tumors (5 to 6 mm in diameter), melphalan induced the longest growth delay, and BCNU the least. Therefore, the relative effects produced by these three drugs in vivo were the same as predicted by SCE induction in vitro. The SCE assay may thus have potential clinical application.
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PMID:Prediction of in vivo tumor response to chemotherapeutic agents by the in vitro sister chromatid exchange assay. 403 20

The effects of the differentiation-inducing polar solvent dimethylsulfoxide (DMSO) on the in vitro response of murine hepatocarcinoma cells to cisplatinum, BCNU, and melphalan were investigated using the sister chromatid exchange (SCE) and cell survival assays. Growth of cells in medium containing 2 per cent DMSO enhanced drug-induced SCEs and cell kill. In order for the enhancement to occur, cells had to be exposed to DMSO for at least 48 h prior to drug treatment. The presence of DMSO during drug treatment did not affect cell response to the three chemotherapeutic agents. The enhancement of chemosensitivity was eliminated within 24 h of DMSO removal. These data suggest that the differentiation-inducing polar solvents may provide antineoplastic benefits when administered in combination with standard chemotherapeutic agents.
Clin Exp Metastasis
PMID:Enhancement of in vitro chemotherapeutic activity by dimethylsulfoxide. 404 62

Chemotherapy for metastatic melanoma was performed in 80 consecutive evaluable patients. DTIC, BCNU and CCNU produced responses in 28% of patients, alone or in combination with each other. Three of 62 patients treated with DTIC remain free of tumor, off therapy at 18-36 months following objective regression of metastases. Chemotherapy with commercially available drugs continued to be uniformly unsuccessful. DTIC was used successfully in treatment of extensive extracranial disease, including one patient with metastatic melanoma during pregnancy. Cerebral metastases were the sole or major cause of death in 8/9 patients who relapsed following control with DTIC for nine months or longer, and one patient developed a carcinoma of the breast following therapy with DTIC and BCNU. Remission was induced in two patients with intralesional BCG, after prior attempts to control metastases with DTIC and combination chemotherapy.
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PMID:Chemotherapy of malignant melanoma with dimethyl traizeno imidazole carboxamide (DITC) and nitrosourea derivatives (BCNU, CCNU). 460 84

The antitumor effects of GANU have been examined in a panel of mouse tumors for which data appear to be lacking in the literature. GANU has significant activity against P388 leukemia and TLX5 lymphoma, and also against the solid tumors B16 melanoma and Lewis lung carcinoma; pulmonary metastases of this tumor are particularly sensitive to the effects of GANU. The effects of GANU on TLX5 lymphoma and Lewis lung carcinoma are less pronounced than those of BCNU and CCNU, as already reported for L1210 leukemia. In contrast with other results obtained with this tumor, chlorozotocin has a less pronounced effect than GANU, and virtually none in lung metastases of Lewis lung carcinoma.
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PMID:Antitumor effects of GANU and other nitrosourea derivatives against transplantable leukemias and solid tumors in mice. 622 44

Eighteen patients with unresectable bronchogenic carcinoma were treated with amphotericin B (7.5 mg/m2 on day 1, 15 mg/m2 on day 2, and 30 mg/m2 on days 3 and 4) plus BCNU (250 mg/m2 on day 4 following amphotericin B) with courses of therapy repeated every 8 weeks. All patients had metastatic disease, and 5 had received prior chemotherapy. Antitumor responses were observed in 8 patients. Six patients had partial responses (greater than 50% decrease in tumor area): 1 of 3 with small cell undifferentiated carcinoma, 1 of 4 patients with large cell undifferentiated carcinoma, 2 of 7 patients with adenocarcinoma, and 2 of 4 patients with epidermoid carcinoma. Two patients had objective improvement (25--50% decrease in tumor area): 1 with small cell undifferentiated carcinoma and 1 with epidermoid carcinoma. The median duration of remission was 3 months. The median duration of survival was 7 months for patients achieving partial response, and only 2 months for other patients. Myelosuppression was the dose limiting toxicity. One patient died with hepatocellular dysfunction, possibly related to BCNU. Transient hypotension was observed in 2 patients. We conclude that amphotericin B plus BCNU produced an encouragingly high response rate in patients with bronchogenic carcinoma, and that a randomized phase III trial is warranted to determine whether amphotericin B enhances the antitumor effects of nitrosoureas or other known antitumor agents.
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PMID:Phase II study of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU, NSC No. 409962) with amphotericin B in bronchogenic carcinoma. 624 43


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