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)

Patients with metastatic nonseminomatous testicular cancer received an induction regimen consisting of bleomycin in 24-hour infusions and bolus iv doses of vinblastine followed by an Adriamycin and cis-dichlorodiammineplatinum(II) combination. Patients achieving complete remission after one or two cycles of this induction chemotherapy were then randomized to receive either radiotherapy (RT) to the previously involved tumor areas or maintenance chemotherapy (MCT) with CCNU, methotrexate, and vinblastine for 2 years. Among 62 evaluable patients, induction chemotherapy achieved 15 (24%) partial remissions and 35 (56%) complete remissions. Two patients with partial remission and single pulmonary metastases were rendered disease-free by surgical resection of residual tumor. Twenty patients received MCT and 15 received RT. To date, median survival is 10,8+ months in the MCT group with five relapses and 12.5 months in the RT group with two relapses. Toxicity in the induction phase was moderately severe with two drug-related deaths.
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PMID:Treatment of metastatic nonseminomatous testicular cancer: a preliminary report of induction chemotherapy followed by maintenance chemotherapy or radiotherapy. 9 36

One hundred and ninety-seven patients with measurable metastatic cancer of the colon have been treated with one of four anticancer drugs which have had little prior trial in this disease. Objective tumor responses lasting a median of 9 weeks occurred with 0.5 g/m of streptozotocin given intravenously every week (10 percent), 130 mg/m of CCNU given orally every 6 weeks (10%), 1.0 mg/kg/day of 6-thioguanine given orally (8%), and 3 mg/kg/day of procarbazine given orally (3%). Performance status declined more rapidly with streptozotocin and 6-thioguanine and the median survival time was less (12 and 16 weeks respectively) than with procarbazine and CCNU (23 and 20 weeks respectively). This study suggests that procarbazine given in this way is ineffective but trials of streptozotocin or 6-thioguanine combined with other agents active against colon cancer should ensue as well as further exploration of the usefulness of other nitrosoureas.
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PMID:Phase II trials with procarbazine (NSC-77213), streptozotocin (NSC-85998), 6-THIOGUANINE (NSC-752), and CCNU (NSC-79037) in patients with metastatic cancer of the large bowel. 12 47

Patients with metastatic renal cell cancer have an overall 5-year survival rate of only 28% to 40% in spite of aggressive surgical treatment. A prospective randomized study conducted by the Eastern Cooperative Oncology Group used methyl--CCNU (meCCNU), vinblastine, and meCCNU-medroxyprogesterone acetate (MPA) to treat 165 patients with advanced renal cancer. The antitumor activity of the single-agent and/or combination therapy is analyzed. Patients were classified (as to grade of anaplasia of tumor; age; performance status; primary site of metastatic disease; and previous treatment with a progestational agent) and randomly assigned to various treatment protocols as described. Crossover randomization to one of alternate single-agent or combination regimens was carried out after failure with initial therapy. 2 meCCNU regimens were associated with severe hematologic toxicity, vinblastine regimens with neurotoxicity. All regimens except the vinblastine-MPA resulted in substantial vomiting. Response rate is low (11%) with each regimen. There were no statistically significant differences in treatment variables or factors among the various regimens. Patients capable of normal activity had a significantly higher response rate and longer survival period than nonambulatory or poor performance status patients. A relatively long symptom-free interval from primary tumor to metastatic disease was also associated with better survival rate. More than 50% of patients exhibited disease progression with 3 months of initiating the regimens.
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PMID:Phase II study of vinblastine, methyl-CCNU, and medroxyprogesterone in advanced renal cell cancer. 35 71

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

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

Untreated meningeal carcinomatosis is a uniformly fatal type of metastatic disease presenting with many protean signs and symptoms. We achieved significant palliation and long-term survival in our patient, using combined chemotherapy and radiotherapy; responses to both intrathecal methotrexate and experimental oral CCNU were observed.
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PMID:Meningeal carcinomatosis. Case report and review of the literature. 94 57

Twenty cases of Ewing's bone tumor, seen at the Orthopaedics Clinic of Padua from 1958 to 1975, were classified into two groups on the basis of results obtained from different schemes of treatment. In the first group of patients, treated during the period 1958-69 by surgery and irradiation, the mean survival rate was one year with two exceptions still surviving since 17 and 11 years respectively (treatment: only amputation). The mean survival rate was prolonged to 5 years in the second group. Here, combined treatment included irradiation (4.000-6.000 r), medical treatment (Adriamycin, CCNU, Vincristine) vaccine therapy and surgery. In the Author's opinion it is more convenient to use the latter therapeutic approach because of the promising results, the improved survival rate and the more effective control of relapses and metastases.
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PMID:[Combined treatment of Ewing's sarcoma]. 123 5

In a consecutive series of studies, 164 patients with symptomatic and/or visceral metastatic malignant melanoma were treated with single agent vindesine, high dose melphalan with autologous bone marrow transplantation (AMBT), high dose BCNU with ABMT or the BOLD (bleomycin, vincristine, CCNU and DTIC) combination. The high dose treatments and the combination chemotherapy resulted in significantly higher response rates but no prolongation of survival. Factors associated with longer survival included the absence of visceral metastases, the absence of bulky disease and good performance status. For all treatments, life table estimates of survival at 1 and 2 years were only 10% and 4% respectively.
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PMID:Chemotherapy for malignant melanoma: combinations and high doses produce more responses without survival benefit. 169 22

Cerebral metastases of malignant melanoma are correlated with a very poor prognosis. Surgery of an isolated metastase can lead to a long survival but the brain lesions are frequently numerous and associated with an extracerebral diffusion. Dacarbazine (DTIC) gives a mean response rate of 21% on visceral localisations but doesn't cross the blood brain barrier (BBB). Neither do the biological response modifiers like Interleukin 2 (Il2) that leads to 25% response rate in disseminated melanoma. Nitrosoureas like carmustine (BCNU) and semustine (CCNU) have been investigated in different non randomised studies and the clinical results didn't illustrate their theorical ability to cross the BBB. Radiotherapy is also used as a palliative therapy with 7 to 16 weeks survival. Fotemustine (muphoran), a new amino acid linked nitrosourea, can give a response rate up to 28.2% in patients with cerebral metastases and the increased survival of responding patients is significant. The availability of this new drug may suggest associations with surgery and radiotherapy in the future to improve the survival of such patients.
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PMID:[Brain metastases of malignant melanomas]. 185 2

Fifty-five evaluable patients with disseminated malignant melanoma were treated with the combination of dacarbazine (DTIC) 400 mg i.v. on days 1 to 3 and lomustine (CCNU) 50 to 80 mg m-2 orally on day 1 with intervals of 6 weeks as the first line chemotherapy. Three (5%) patients had complete and 6 (11%) partial response, and 7 (13%) patients had stable disease at least for 3 months. The patients with an objective response (n = 9) survived longer than the rest of the patients if the length of survival was calculated from the start of chemotherapy (P = 0.0006). However, the responding patients also had longer time interval from the diagnosis to the detection of distant metastases (P = 0.05), and survival time from disease progression following DTIC and CCNU therapy (P = 0.005). These findings suggest that patients with an objective response to DTIC-CCNU therapy have melanoma with a slow progression rate, and prolonged survival in such patients may in part result from the less aggressive biological nature of their tumours.
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PMID:Association between chemotherapy response and rate of disease progression in disseminated melanoma. 198 56


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