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

A 12 1/2-year-old female presented with Ewing's sarcoma of the manubrium sterni which extended into the anterior mediastinum. At presentation there was no evidence of metastatic disease. Her initial treatment consisted of radiation therapy and chemotherapy. The residual tumor was subsequently resected and the sternal defect was repaired with Marlex mesh. Postoperatively, she was maintained on chemotherapy consisting of BCNU, cyclophosphamide, and adriamycin. The adriamycin was discontinued after she developed sterile fibrinous pericarditis. She remains free of her disease two years after diagnosis. Although extremely rare, Ewing's does occur in the sternum and this area is amenable to wide local resection without severe functional disability.
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PMID:Primary Ewing's sarcoma of the sternum: a case report. 11 17

While carcinomas of the stomach is decreasing in incidence in the Dnited States, it is still a major cause of cancer death. But gastric neoplasms are not decreasing in some other geographic areas. According to some studies, 30% of all cancer in the U.S.S.R. originates in the stomach. The rate of gastric neoplasms is greatest in Japan, and over 54% of all cancer in the male population arises in the stomach. The peak age for development of stomach cancer is between 70 and 80 years; over 60% of all stomach cancer is diagnosed in patients between the ages of 60 and 70, while more than 10% is found in those over 80. The main hope for cure at this time rests with surgical treatment. However, despite increased use of surgery, the 5-year survival rate of approximately 13% for patients diagnosed during 1955-59 has not improved to any degree since that time. The major drugs commonly used to treat gastric cancer are 5-fluorouracil (5-FU) and mitomycin C. Controversy still exists concerning the optimum method for administering 5-FU, the most frequently used drug in the United States. The standard loading-course method was attended by a high risk of severe toxicity and drug-related deaths. Several variations of the loading course have evolved. Currently, the Mayo Clinic group uses a 5-day course of 13.5 mg 5-FU/kg repeated every 5 weeks, with therapy interrupted if stomatitis or diarrhea develops; with this regimen the drug-related mortality rate was reported to be less than 1%. Studies have shown that 5-FU plus radiotherapy can enhance survival in patients with locally unresectable diseases. The overall objective with 5-FU is 20-25% with an average of 4-5 months' duration of response. Despite the many patients treated with 5-FU, rarely has a systematic analysis been done of factors such as age, sex, disease-free interval, histologic grade of the tumor, or sites or metastases, which might predispose to a favourable or unfavorable response. In Japan the most commonly used drug for treatment of gastric cancer is mitomycin C, the second most frequently used drug in the United States. The overall objective response rate with mitomycin C is between 20 and 30%, with the higher response rates being reported in the Japanese data. The average duration of response ranges from 1 to 3 months. The nitrosoureas [1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), 1,3-cis(2-chloroethyl)-1-nitrosourea (CCNU), and methyl CCNU (MeCCNU)] have shown some evidence of activity against gastric cancer. BCNU has yielded an objective response rate of 18% (6/33) and an average duration of response of 4.5 months in gastric cancer patients, most of whom had no prior therapy. Adriamycin recently has been shown to have some antitumor activity, with an approximate response rate of 25%. Combination approaches have been more successful in stomach cancer than in any other gastrointestinal neoplasm. The Japanese have reported higher response rates with a combination of 5-FU, mitomycin C, and cytosine arabinoside...
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PMID:Gastric cancer: current status of treatment. 40 78

Thin slices of s.c. implanted B-16 melanomas as well as of human melanomas have been incubated for 5 h with (H3) Uridine and (H3) Thymidine in the presence of different chemotherapeutical agents, whose concentration was equivalent to the tenfold therapeutical daily dose in men. In this short term test model, the sensitivity of a melanoma to a chemotherapeutical agent is indicated by the inhibition of the nucleoside uptake by more than 50%. The in vitro sensitivity rates, each based on 10--30 melanomas, are compared to the in vivo sensitivity rates. Sensitivity is indicated by the increase of life span (greater than 25%) in the melanoma bearing mice respectively by the regression of human melanoma metastases (greater than 50%). -- The in vivo sensitivity of the B-16 melanomas, evaluated by the uridine and/or thymidine uptake, was in line with the in vivo sensitivity to all chemotherapeutical agents with the exeption of Adriamycine and DTIC. The in vitro sensitivity of human melanomas to Dactinomicine, Vincristine, BCNU and DTIC corresponds to the in vivo sensitivity whereas no in vitro/in vivo correspondence could be observed in testing Bleomycine, Procarbacine and 5-Fluorouracile. Comparing the sensitivity of B-16 and human melanomas, similarity was observed in vitro but not in vivo.
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PMID:[In vitro and in vivo sensitivity of animal and human melanomas to various chemotherapeutical agents]. 56 19

Fifty patients with metastatic malignant melanoma were randomized to treatment with either DTIC (2 mg/kg/day X 10 iv) or the combination of BCNU (150 mg/m2 iv) plus vincristine (VCR) (2 mg/m2 iv on Day 1 only). Treatment failures were crossed over to the alternate therapy. Primary, secondary, and cumulative response rates to DTIC were 29%, 9%, and 22%, respectively. Primary, secondary, and cumulative response rates to BCNU plus VCR were 23%, 29%, and 25%, respectively. Five of 26 patients (19%) experienced objective regression from secondary therapy after failure to respond to primary therapy. DTIC produced gastrointestinal and hematologic toxic effects; BCNU plus VCR produced gastrointestinal, hematologic, and neurologic toxic effects. VCR administered at a dose of 2 mg/m2 resulted in excessive neurologic toxic effects in 12 of 21 patients; a maximum VCR dose of 2 mg/injection was well tolerated by 15 subsequent patients without an adverse effect upon response rate. An analysis of tumor burden and organ involvement in responders and nonresponders suggests that DTIC is the first-choice treatment for patients with limited tumor burdens and nonvisceral metastases; BCNU plus VCR is the first-choice treatment for patients with extensive tumor burdens and visceral-predominant disease. However, failure to respond to primary therapy does not preclude response to secondary therapy with the alternate regimen.
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PMID:Randomized prospective trial of DTIC (NSC-45388) alone versus BCNU (NSC-409962) plus vincristine (NSC-67574) in the treatment of metastatic malignant melanoma. 79 78

Forty patients with disseminated malignant melanoma were treated with triple combination chemotherapy consisting of Imidazole Carboxamide, BCNU and Vincristine. Seventeen of 40 patients (42.5%) showed significant responses including three complete responses. Responses were seen in cutaneous, lymph node and pulmonary metastases. Nine instances of hepatic metastases were unaffected by therapy but 68% of the skin and nodal patients responded. The median response duration was only 4 months and the median survival of responders was 9.5 months compared to a 2 month median survival of non-responders. Half of the responders died of CNS metastases. The short duration of response, the resistance of hepatic metastasis and the high incidence of cerebral recurrence necessitate additional therapeutic approaches to this disease.
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PMID:Combination chemotherapy of malignant melanoma with imidazole carboxamide, BCNU and vincristine. 83 50

Thirty-two evaluable patients with metastatic carcinoma of the breast received chemotherapy consisting of BCNU plus cyclophosphamide followed in 18 hours by Adriamycin. Treatments were repeated every 4 weeks. Complete or partial responses were observed in 14 patients (43.7%) and in 12 of 27 drug-resistant patients (44.4%). An additional 26% of patients had objective improvement, for an overall objective response rate of 70.4% in drug-resistant patients. Skin, lymph node, and soft tissue metastases more frequently responded to therapy, while hepatic, peritoneal, and osseous metastases responded with an intermediate frequency. Pulmonary, pleural, and central nervous system metastases did not respond to therapy. The median duration of complete and partial responses was 6.8 months, and the median survival of these patients was 9.6 months. Overall, the median survival of all patients in this study was 6.5 months. The dose-limiting toxicity was myelosuppression, particularly granulocytopenia. Congestive heart failure and stomatitis were rare. This combination of drugs is a reasonably well-tolerated regimen for treating advanced breast carcinoma in an ambulatory setting, and produces a high rate of objective antitumor response of moderate duration.
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PMID:Adriamycin, 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU, NSC 409962) and cyclophosphamide therapy of drug-resistant metastatic breast carcinoma. 90 47

Immunological investigations in malignant melanoma have demonstrated the important role of immunological defence mechanisms in the control of tumour growth and tumour spread. On the basis of the different test systems for investigation of immunecompetence and tumourspecific immunity it was possible to demonstrate that patients with melanoma, especially of clinical stages II and III, have a weak, sometimes an anergic immune reaction against their own tumour. The information obtained from in vitro and in vivo studies in human on tumour immunity formed the rational basis for immunotherapy in malignant melanoma. Increasing evidence suggests that active non-specific immunotherapy and, especially, active specific immune-stimulation with inactivated melanoma cells can delay the appearance of distant metastases and result in an improved survival rate for patients with involved regional lymph nodes. At present the use of involved chemotherapy is mostly confined to patients with disseminated malignant melanoma. The most extensively used chemotherapeutic agent for treatment of melanoma is the DTIC (dimethyl-triaceno-imidazole-carboxamide). The objective response rate with this monotherapy has been reported to be up to 25%. Nitrosoureas (BCNU, CCNU, MECCNU) have also been widely used and have brought clinical responses similar to DTIC. Experimental studies in animal models and investigation in human have demonstrated that chemotherapy can be combined successfully with immunotherapy with a potential additive, perhaps synergistic, effect.
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PMID:[Immunology and therapy of malignant melanoma (author's transl)]. 90 25

The Madison 109 (M109) tumor was discovered in 1964 in the lung of a BALB/c mouse. This experimental carcinoma is maintained in vivo by sc passage in the right axillary region. When implanted im (5 X 10(5) cells) into the right hind leg of BALB/c mice for testing, the primary progresses with metastases to the lung, spleen, and liver. The metastases to the lung are visible within 3 weeks and result in the death of the host in about 35 days after tumor implant. Implantation of a lung nodule is tumorigenic and lethal. Pyran polymer therapy delayed the appearance of lung metastases, inhibited the growth of the primary tumor, and significantly increased the lifespan of BALB/c mice inoculated with the M109 tumor. No spontaneous regression has been observed and very few "no takes" have occurred in untreated BALB/c mice inoculated with at least 500 M109 cells. Of the 82 agents tested so far, the M109 model has selected active agents such as actinomycin D, adriamycin, daunorubicin, DNA, procarbazine, and pyran polymer. It has not shown sensitivity as tested to several standard therapeutic agents including cytosine arabinoside, BCNU, hydroxyurea, mechlorethamine, melphalan, triethylenemelamine, and vincristine.
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PMID:Characterization and responsiveness of the Madison 109 lung carcinoma to various antitumor agents. 92 51

Twenty-one patients with advanced metastatic cancer received amphotericin B (AmB) plus BNUC in a Phase I chemotherapy trial. Of 11 patients with measurable metastases from bronchogenic carcinoma, five had partial antitumor responses lasting 1.5 to 12+ months, and one had objective improvement. Only two of six patients with other types of tumors had objective improvement of short duration. No consistent evidence of immunologic stimulation was observed in eight patients studied. These results suggest that amphotericin B may increase the therapeutic ratio of BCNU, and further trials of this new concept in chemotherapy of advanced tumors are in progress. The dose-limiting toxicity was myelosuppression, usually thrombocytopenia. No enhancement of BCNU toxicity by the addition of AmB was observed. The recommended dose for future studies is: AmB, 7.5 mg/m2 on day 1, 15 mg/m2 on day 1, 30 mg/m2 on days 3 and 4; plus BCNU, 250 mg/m3 on day 4. The regimen is repeated every 6 to 8 weeks.
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PMID:Amphotericin B plus 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU-NSC no. 409962) in advanced cancer. Phase I and preliminary phase II results. 99 Nov 5

The therapeutic results of a controlled study with three multiple-drug regimens (regimen A: DTIC, vincristine, BCNU; regimen B: DTIC, vincristine, hydroxyurea; and regimen C: DTIC, actinomycin D, BCNU) in a total of 274 evaluable patients with advanced malignant melanoma are reported. CRs were significantly more frequent (P less than 0.01) in regimens A (9.3%) and C (16.4%) compared with regimen B (1.1%). No significant difference in terms of CR plus PR was detected among the three regimens. In all regimens a higher number of CRs plus PRs was seen in patients with soft tissue metastases only, compared with those who had visceral involvement. In all three regimens patients achieving CR showed a longer duration of response and survival in comparison with patients achieving PR. The incidence of brain metastases was neither lowered nor delayed by the presence of BCNU in regimens A and C.
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PMID:Comparative evaluation of three combination regimens for advanced malignant melanoma: results of an international cooperative study. 100 May 18


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