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)

In a phase-II study 46 patients with advanced colorectal cancer were treated with the new nitrosourea ACNU [1-(2-chloroethyl)-1-nitroso-3 (4-amino-2-methyl-5-pyrimidinyl)methyl-3-nitrosourea]. From 43 evaluable patients, 86% presented distant metastases and 14% an unresectable primary tumour or a recurrent tumour. 24 patients presented a colon and 19 a rectal cancer. Prior anticancer drug treatment was given to 34 patients (79%), 11 (26%) were pretreated with a nitrosourea. ACNU was administered every 4-6 weeks as a single intravenous push injection of 100 mg/m2. Most patients received 2-3 courses. From 43 evaluable patients, one patient achieved a complete and 3 a partial remission (CR + PR 9%). 5 patients reached a minimal regression (tumour regression of less than 50%) and 5 a no change for at least 2 months. The median duration (time from beginning of ACNU therapy until tumour progression) of the 14 responders was 132 days. The median survival time was significantly longer for responders in comparison to patients with progressive disease (9.8 versus 4.1 months). The dose limiting toxicity was delayed bone marrow suppression predominantly in the form of thrombocytopenia. 22/42 patients (52%) presented a thrombocytopenia of under 50.000/mm3 with a nadir after 27 days. Leucocytopenia under 2.000/mm3 were observed in 22/40 patients (30%). A fall of haemoglobin of more than 2 g/dl was seen in 71%. Nausea or vomiting over 1-2 days were found in 59% of the treatment courses. Other drug related side effects were not encountered. ACNU has a similar activity in colorectal cancer as BCNU and CCNU.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Phase II study of the water-soluble nitrosourea compound ACNU in advanced colorectal carcinomas]. 639 65

When a malignant tumor spreads to the brain, its concurrent growth outside of the Central Nervous System (CNS) and the devastating effects of cerebral metastases offset often all therapeutic attempts. The disappointing results commonly achieved in the management of intracranial metastases are only partly explained by the low efficacy of available therapeutic modalities. Support therapy plays the major role in the management of patients harboring cerebral metastases. Corticosteroids and osmotic agents can rapidly improve neurological symptoms, allowing a rapid, even if frequently brief, amelioration of the quality of life. Immunotherapy cannot be considered as an effective therapeutic tool for metastatic brain tumors. For many years chemotherapy has been thought inadequate treatment for both controlling the growth of metastases and improving neurological impairment . However the new concepts of multimodality therapy of primary CNS tumors seem to be applicable even to intracranial metastases. In combination with corticosteroids and radiation therapy, nitrosourea compounds (BCNU and CCNU) proved to be effective in more than 1/3 of patients in prolonging survival. New possibilities of improving available results are expected from new antiproliferative drugs (cisplatin) and from new modalities of administering conventional cytotoxic agents (intra-arterial route).
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PMID:[Chemotherapy, immunotherapy and supportive therapy in cerebral metastases]. 642 1

Actuarial progression-free survival rate at 5 years of a series of 34 patients with medulloblastoma treated by combined surgery, radiotherapy, and chemotherapy was 71%. No relapses were observed in 14 patients followed for more than 5 years. Treatment consisted of a short postoperative course of vincristine (VCR) and intrathecal (IT) methotrexate (MTX) followed by irradiation to the entire cranio spinal axis. Maintenance chemotherapy (CCNU, VCR, and IT MTX) was then continued to encompass 2 years from surgery. Failure occurred in nine patients: four had local recurrence, four dissemination within the central nervous system, and one widespread skeletal metastases. Poor prognostic factors such as presence of malignant cells in the cerebrospinal fluid, non-radical surgery, young age, and radiation doses less than 50 Gy to the tumor bed, did not adversely affect the outcome of patients in this series. Long-term sequelae from the treatment program could be observed in all patients, and in 58% they were severe enough to interfere with normal, active life.
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PMID:Medulloblastoma. Results of a sequential combined treatment. 647 30

A total of 49 patients were treated using intraarterial cis-platinum infusions at a dose of 100 mg/m2. The patients were separated into three groups. There were 13 patients with metastatic tumors, 10 with recurrent malignant gliomas, and 22 patients with high-grade gliomas who received intraarterial cis-platinum as part of an adjuvant program. In addition, four nongliomatous primary brain tumors were treated in this fashion. Cis-platinum was filtered immediately prior to intraarterial infusion using a 0.22-micron filter. Response to treatment was evaluated by follow-up CAT scans and neurologic examinations. There were three complete and eight partial responses in metastatic tumors, and eight partial responses in recurrent gliomas. The median survival was 19 weeks for patients with metastatic disease, and 16 weeks for patients with recurrent gliomas. Those high-grade glioma patients who received intraarterial cis-platinum as adjuvant chemotherapy along with CCNU and radiation therapy had a projected median survival of 91+ weeks. Toxicity from intraarterial cis-platinum following drug filtration was markedly reduced when compared with previous reports. Only five patients experiencing visual or central nervous system toxicity utilizing filtered cis-platinum and no radiographic or histopathologic evidence of central nervous system toxicity was observed. Bilateral deafness was observed following vertebral artery infusion in both patients treated in this manner and thus vertebral artery infusions should be avoided. Systemic toxicity was mild. Intracarotid infusion is a safe, well-tolerated delivery system for filtered cis-platinum with a high response rate for patients with both metastatic and primary malignant brain tumors.
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PMID:Intraarterial cis-platinum chemotherapy for patients with primary and metastatic brain tumors. 654 19

Between the years 1973-1977, 152 male patients from 28 participating Veterans Hospitals with histologically proven nonresectable cancer of the pancreas were randomized in a two-arm study. The treated group was to receive combination chemotherapy with 5-FU and CCNU, and the controls were to receive no chemotherapy. Both groups were comparable with respect to age, amount of weight loss, extent of histologically proved metastases, and operation performed. In the treatment group, drug therapy was begun between 10 and 60 days postoperatively. Intravenous 5-FU, 9 mg/kg, was administered on five consecutive days, and CCNU, 70 mg/m2, was given orally on the first day of each course. In the absence of toxicity, the course was repeated every six weeks for life; 146 drug courses were given. The incidence of toxicity was not great. One or more toxic reactions were reported for one-third of the drug courses administered, but for the most part, these were mild. The most frequent toxic reaction was vomiting in 17% of the courses, and hematologic toxicity-primarily leukopenia-in 15% of the drug courses. There was no evidence of a beneficial effect on survival from drug treatment in the group as a whole or in any subgroup analyzed. The median survival of the control group was 3.9 months, and of the drug-treated group, 3.0 months.
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PMID:Randomized study of 5-FU and CCNU in pancreatic cancer: report of the Veterans Administration Surgical Adjuvant Cancer Chemotherapy Study Group. 700 90

Survival rates for patients with colorectal cancer have remained unchanged during the last 30 years. Every third patient with colon cancer Dukes' C and every fourth patient with rectal cancer Dukes' C survives 5 years. Of the patients who succumb to colorectal cancer, 85% will die within 3 years from diagnosis. There are many studies concerning the mechanisms of adjuvant chemotherapy. Its effectiveness has been proven in animal experiments. Micrometastases have a large growth fraction, few non-proliferative cells, and because of this, increased sensibility to cytostatics. Adjuvant chemotherapy aimed at treating occult metastases. In colorectal cancer the combination of 5-FU and Nitrosurea has been shown to have a better effect than 5-FU alone. Grage et al. have shown patients with colorectal cancer Dukes' C to have a longer tumour-free interval with adjuvant 5-FU, and this treatment gives patients with rectal cancer a prolonged survival time. In an adjuvant study, peroral 5-FU 90 days versus placebo did not show any effect. In another adjuvant study Vincristin, CCNU and 5-FU treated patients had fewer tumour recurrences than control patients. The observation time is, however, rather short. Adjuvant chemotherapy for colorectal cancer has shown promising results and it is hoped that further attempts with other forms of cancer in the gastrointestinal tract will also yield the same results.
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PMID:[Background and experience of adjuvant cytostatic therapy in gastrointestinal cancer (author's transl)]. 703 99

To study the usefulness of an in vitro colony-forming assay in predicting individual clinical responses to chemotherapy, tumor cells obtained from 150 melanoma metastases (119 patients) were grown in soft agar according to the method of Courtenay and Mills (1978), and tested for sensitivity to DTIC, CCNU, vinblastine, procarbazine, abrin and ricin. In 83% of the cases colony formation was observed (plating efficiency, PE, greater than 0.01%). Twenty-seven per cent of the tumors gave PEs greater than 1%, 45% gave PEs in the range 0.1-0.9%, whereas 11% of the tumors gave 0.01-0.09%. The PEs were not correlated with the degree of pigmentation or with the clinical course. Evaluable chemosensitivity data were obtained on 104 metastases from 83 patients. Large differences in sensitivity were seen. In cases which were evaluable both in vivo and in vitro a clear correlation was found between the in vitro chemosensitivity, expressed as the expected growth delay, and the clinical response to chemotherapy. Tumors from patients with partial response, mixed response or stable disease after prior progression, all had rather high in vitro sensitivity to the drug used (expected growth delay greater than 2.0), whereas patients with progression had lower sensitivity. The results confirm that the soft agar method used here provides good culture conditions for human melanoma cells and show that chemosensitivity data can be obtained in a high percentage of melanoma patients. The approach used seems promising in aiding clinicians to adjust chemotherapy to individual patients.
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PMID:Colony growth and chemosensitivity in vitro of human melanoma biopsies. Relationship to clinical parameters. 709 99

Forty-seven children with histologically confirmed medulloblastoma are considered. Forty-five cases were surgically by direct approach to the tumour, while two cases were treated only with a shunt. A shunt was inserted preoperatively in 14 cases, postoperatively in 4 cases. Surgical resection was total or subtotal in 52% of cases, partial in 35%, and limited to a biopsy in 13%. Radiation treatment to the entire neuraxis was done in 37 cases: 10 of these cases received additional chemotherapy--mostly with CCNU--as primary treatment for medulloblastoma. Ten patients died within 30 days after surgery. Twenty-two patients died months after treatment, mainly from tumour recurrence (19 cases). One patient was lost to follow-up. Thirteen patients are survivors from 10 months to 20 years after treatment. As a whole, the one year survival rate has been 67%, 3 year survival 43%, and 5 year survival 27%. Complications affecting prognosis have been presented by tumour recurrence and metastases. CSF shunting and lack of prophylactic irradiation to the cerebral hemispheres have been considered responsible for the high incidence of supratentorial metastases in our series. Factors influencing prognosis have been the extent of tumour resection and association of primary chemotherapy with radiotherapy. Within 3 years after surgery survival has been 52% in cases with total resection against 31% in cases with partial resection of tumour. As regards chemotherapy, 3 year survival has been 60% for patients with combined treatment (chemo- and radiotherapy) against 37% in patients with radiotherapy alone. It is concluded that the best results in children with medulloblastoma are achieved by a radical resection, associated with a combined primary treatment of radiotherapy and chemotherapy.
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PMID:Treatment of medulloblastoma in children: long-term results following surgery, radiotherapy and chemotherapy. 728 44

A chemotherapy regimen consisting of dacarbazine (DTIC), vincristine, bleomycin and lomustine (CCNU) was combined with natural leucocyte interferon (IFN) in the treatment of 37 patients with cutaneous and subcutaneous metastases of malignant melanoma. Twenty-five also had concomitant lymph node, visceral, bone or brain metastases. Fifteen patients (41%) experienced complete response (CR) and 10 (27%) partial response (PR) of the superficial lesions. In addition, three patients were rendered surgically tumour-free after PR or disease stabilization during drug therapy. The median overall duration of response was 10.2 months (range 1-53 months). In disseminated disease, the combined therapy produced favourable results, particularly with regard to superficial lesions. It is also possible that this therapy may retard the growth of aggressive subcutaneous metastases in patients who have previously had multiple surgical procedures in an attempt to stabilize their disease. In a small proportion of patients, the long-term complete remission with the drug therapy alone, or in combination with surgery, suggests that this regimen might have been curative.
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PMID:Response of subcutaneous and cutaneous metastases of malignant melanoma to combined cytostatic plus interferon therapy. 754 96

The standard therapy for advanced non-small cell lung cancer (NSCLC) remains to be defined. The poor results from chemotherapy have favored the search for prognostic factors that help identify patients more likely to respond. Our objective was to find factors related to response, the duration of response, and overall survival in patients with advanced NSCLC. We reviewed the clinical records of 292 patients with non-operable NSCLC, all of whom had a good performance status and had received chemotherapy. Ninety percent were male and the median age was 59 years. The therapeutic regimens included MACC (methotrexate, adriamycin, cyclophosphamide and CCNU), cisplatin + vindesine or etoposide, MIP (mitomycin, ifosfamide and cisplatin) and MVP (mitomycin, vindesine and cisplatin). In the multivariate analysis, a normal albumin level and the inclusion of cisplatin were related to the achievement of a response (40% if both favorable factors were present). No factors appeared related to the duration of response. The following factors were predictive for survival: weight loss, performance status, lymphocyte count, albumin level, number of metastases and the presence of bone metastases. We conclude that the albumin level identifies a group of patients with advanced NSCLC who are more likely to respond to cisplatin-containing chemotherapy.
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PMID:Serum albumin and other prognostic factors related to response and survival in patients with advanced non-small cell lung cancer. 760 32


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