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)

Thirty-four patients with advanced breast cancer, who had not received previous chemotherapy for metastatic disease, were treated with mitoxantrone 14 mg/m2 i.v. every 21 days. Eleven of 33 evaluable patients (33%) achieved a partial response; there were no complete responders. Before commencing mitoxantrone, and 3-monthly thereafter, radionuclide assessment of ventricular performance was obtained at rest and in response to stress. Ten patients showed a deterioration in ejection fraction, two of whom developed congestive cardiac failure. Dose-limiting toxicity was myelosuppression. Nausea and vomiting were generally mild and transient. Alopecia was minimal in most patients. Mitoxantrone is an active, well-tolerated new drug in the treatment of advanced breast cancer, but cardiotoxicity may occur in a proportion of patients. Further investigation is required to determine the precise nature, incidence and prognosis of cardiotoxicity encountered with mitoxantrone.
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PMID:Mitoxantrone in advanced breast cancer--a phase II study with special attention to cardiotoxicity. 654 Jan 79

In an effort to evaluate the toxicities and anti-tumor efficacy of the combination of high-dose cyclophosphamide (CY) and carboplatin, we undertook a phase I-II trial with autologous bone marrow (BM) or peripheral blood stem cell (PBSC) rescue for patients with solid tumors. Forty three patients, 39 of whom had either high risk stage II or III or metastatic breast cancer were treated with escalating doses of carboplatin 1200-1800 mg/m2 and cyclophosphamide 4800-6000 mg/m2 over 3 days followed by autologous BM or PBSC infusion. No life-threatening or fatal toxicities were observed. Reversible congestive heart failure was seen in two patients. Transient hepatotoxicity, characterized primarily by elevation of transaminase levels, and nausea and vomiting, adequately managed with anti-emetic therapy, were seen in 39 and 40 of 43 patients, respectively. The 14 month post-transplant probability of relapse-free survival for 26 patients with high risk II-III breast cancer was 79%; for 13 patients with metastatic disease, the 22 month relapse-free survival probability was 23%. High-dose carboplatin and CY at maximally administered doses of 1800 mg/m2 and 6000 mg/m2 is a well tolerated preparative transplant regimen for autologous BM or PBSC transplantation. It appears to have similar anti-tumor activity and an improved safety profile when compared with other commonly employed transplant preparative regimens.
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PMID:Phase I-II trial of high-dose cyclophosphamide, carboplatin and autologous bone marrow or peripheral blood stem cell rescue. 765 78

Thirty-two eligible patients with advanced metastatic breast cancer who had received no more than 1 prior chemotherapy regimen for metastatic disease (16 had received prior doxorubicin) were treated with piroxantrone at a dose of 120 mg/m2 intravenously every 21 days. In the twenty-seven patients evaluable for response, two partial responses were seen. Toxicities observed were primarily hematologic with grade 3 or greater granulocytopenia occurring in 34% of the patients. One patient developed symptomatic congestive heart failure at a total cumulative dose of 960 mg/m2. We conclude that piroxantrone given at this dose and schedule has minimal activity in patients with metastatic breast cancer.
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PMID:Phase II trial of piroxantrone in metastatic breast cancer. A Southwest Oncology Group study. 777 36

A 80 year old man, in general good health, presented with a rapidly progressive congestive heart failure, without response to treatment. At echocardiography, there were masses in the right atrium and ventricle. The patient deceased two months after the first clinical manifestations. At autopsy, we found a massive right-sided atrio-ventricular infiltration by a malignant non-Hodgkin's lymphoma of centroblastic type, causing a subtotal obstruction of the tricuspid and pulmonary valves. We observed also four intestinal metastases without other manifestations of lymphoma.
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PMID:[Primary cardiac lymphoma with obstructive cardiac insufficiency]. 781 71

Between February 1990 and December 1991 high-dose epirubicin (Epi)(120 mg/m2) plus cyclophosphamide (CTX)(600 mg/m2) were given every 3 weeks to 52 patients with locally advanced and metastatic breast cancer. 26 patients with locally advanced disease received four courses of this regimen before and after local treatments. 26 patients had metastatic disease: they received eight courses unless progression or unacceptable toxicity occurred. Responses were seen in 37/48 (77%) evaluable patients including 14 complete responses (CR), 23 partial responses (PR), nine stable disease, two progressive disease. Among the 25 evaluable patients with locally advanced disease, 9 had a CR and 11 a > 80% decrease in tumour volume. 6 patients (24%) had a pathologically confirmed complete response. 18 patients (72%) had a tumour reduction to 0-2 cm. The 3-year disease-free survival was 60%. Of the 23 evaluable patients with metastatic disease, 5 obtained a CR and 10 a PR, yielding an overall response rate of 65%. Myelosuppression was substantial with a grade 3-4 leucopenia in 76% of the patients even if neutropenic fever occurred in only 7% of the courses. A clinical congestive heart failure occurred in 1 patient following a total Epi dose of 960 mg/m2 and a bilateral quadrantectomy and radiotherapy. We conclude that (1) high-dose Epi + CTX is a very active regimen, in particular for the patients with locally advanced breast cancer; (2) breast conservation after this regimen in some of these patients may be considered; (3) neutropenia is the dose-limiting toxicity. Currently, a phase II study using the same combination given every 2 weeks together with r-methuG-CSF is ongoing.
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PMID:Phase II trial of high-dose epirubicin and cyclophosphamide in advanced breast cancer. 799 14

Metalloproteinases, inhibitors of metalloproteinases, plasminogen activators, inhibitors of plasminogen activators and cathepsins are thought to be involved in invasion by tumor cells. Glioblastoma multiforme is highly malignant and extremely refractory to therapy. One reason is because of its highly invasive nature within the nervous system. However, it remains unclear how invasion/dissemination of glioblastoma multiforme proceeds. In this study, we attempted to determine which proteinases were responsible for the invasion activity of human glioma cell lines in vitro. Nine human glioma cell lines (NHG1, NHG2, IN157, IN301, IN500, U251, U343, T98G and CCF-STTG1) derived from patients with glioma were grown in culture and used. We compared the invasion activity of glioma cell lines in a Matrigel invasion assay system, and formulated the activity as invasion index (%). Among the nine cell lines, IN157, IN500 and U343 showed less than 10% invasion activity (low group); NHGI, IN301 and CCF-STTG1 showed 10-25% activity (intermediate group); NHG2, U251 and T98G showed more than 30% activity (high group). Addition of an inhibitor of metalloproteinases, TIMP-1, to the assay system was found to significantly inhibit invasion activity of T98G cells (P < 0.01). Northern blot analysis demonstrated expression of urokinase-type plasminogen activator (uPA), tissue-type PA (tPA) and PA inhibitor-1 (PAI-1) in some of the above cell lines. Cellular levels of PAs and their inhibitor mRNA, however, appeared not to be correlated with invasion activity in most glioma cell lines except for CCF-STTG1. Expression of 72 kDa type IV collagenase (MMP-2) was much lower in IN157, IN500 and U343 than other cell lines, whereas expression of TIMP-1 was much higher in IN500 than in other cell lines. Zymographic activity was found to be comparable to MMP-2 mRNA levels in all cell lines except for CCF-STTG1. Type IV collagenolytic activity was also comparable to invasion activity in nine cell lines. These observations suggest the role of type IV collagenase and its inhibitors in determining capacity for invasion by human gliomas. However, a comprehensive analysis both in vitro and in vivo is required to confirm the role for this enzyme in glioma cell invasiveness.
Clin Exp Metastasis 1994 Jul
PMID:Expression of 72 kDa type IV collagenase and invasion activity of human glioma cells. 803 4

The long-term efficacy of the positive inotropic and vasodilator drug, pimobendan, was assessed in 21 patients suffering from symptomatic heart failure. Patients were randomized to 16 weeks of double-blind therapy with either 2.5 or 5.0 mg/day of pimobendan (n = 10), or a matching placebo (n = 11). Patients were blinded on the study drug if their clinical status had not substantially worsened during the study. Of the placebo-treated patients, 5 patients were withdrawn from the study because of a deterioration of their heart failure, while none of the active treated group was withdrawn because of increased symptoms. Quality of life, assessed by the specific activity scale derived from the metabolic costs of individual physical activity, was 3.45 +/- 0.90 (SD) mets in the baseline state and increased significantly after week 16, averaging 5.07 +/- 1.40 and 4.67 +/- 1.47 mets at weeks 16 and 24, respectively. In the placebo-treated group, the specific activity scale was 3.27 +/- 1.21 mets at the baseline and remained unchanged throughout the study period. Patients treated with pimobendan were able to significantly increase their exercise duration. The accompanying increase in peak oxygen uptake was statistically insignificant, due to the limited number of patients enrolled in the study. These results suggest that in contrast to the recent pessimistic view of the long-term efficacy of cardiotonic drugs, pimobendan is beneficial in treating patients with congestive heart failure and may favorably modify their prognosis. Further large-scale evaluation of this agent is warranted.
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PMID:Clinical effects of long-term administration of pimobendan in patients with moderate congestive heart failure. 805 17

The authors report their experience with octreotide in 20 patients (median age 57 years, 10 M, 10 F) from 1984 to 1991; 16 had metastatic APUDoma: 1 PPoma with VIPoma, 1 glucagonoma, 5 gastrinoma including 1 associated to PP-oma, 9 mid-gut carcinoid; 3 patients had multiple-endocrine neoplasia type I (MEN-I) with Zollinger-Ellison syndrome (ZES) and 1 patient a non-metastatic VIPoma. Octreotide (200-750 micrograms/day) was administered bid or tid with regular laboratory controls and morphological assessment. There was a striking improvement of symptoms, particularly in the carcinoid group (reduction of flushing in all patients and of diarrhoea in 3/5), in the patient with gastrinoma + acromegaly (regression of congestive heart failure) and in the patient with non-metastatic VIPoma. The hormonal markers were markedly reduced, particularly gastrin, PP (except in the patient with PPoma + VIPoma), VIP, GH and Somatomedin-C and urinary 5HIAA in 4/9 patients with carcinoid. There was only one partial regression of metastases (gastrinoma) and 4 apparent stabilizations of tumour growth, in the 16 metastatic cases. Among them, 4 patients died: 1 glucagonoma, 1 PPoma + VIPoma, 2 mid-gut carcinoids after a treatment of 5, 16, 30, 36 months, respectively. The patient with acromegaly + ZES died after 6 years of treatment at age 81. A patient with prolactinoma, resected insulinoma, hyperparathyroidism and ZES was not improved by a short course of octreotide (hypoglycemia); he died later of recurrent insulinoma. In conclusion, octreotide is a useful drug to control most of the symptoms related to gut endocrine tumours; it may inhibit tumour growth.
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PMID:Use of octreotide in the treatment of digestive neuroendocrine tumours. Seven year experience in 20 cases including 9 cases of metastatic midgut carcinoid and 5 cases of metastatic gastrinoma. 826 71

Pleural effusion (PE) has been increasingly diagnosed over the last eight years in the Department of Internal Medicine of the Centre Hospitalier of Kigali, Rwanda. To determine the etiology of PE and to examine its possible association with HIV-1 infection and tuberculosis (TB), the authors performed an etiological work-up, including thoracocentesis and pleural punch biopsy, of all new patients with PE of undetermined etiology referred to the Division of Pulmonary Diseases at the hospital between September 14, 1988, and October 16, 1989. 81 men and 46 women of mean age 34 years were enrolled in the study. Pleural TB was diagnosed in 86% and confirmed histologically and/or bacteriologically in 82%. 82 of the 98 pleural TB patients tested for antibody to HIV-1 were HIV-1-seropositive. Metastatic cancer was responsible for PE in six patients, Kaposi's sarcoma in three, lymphoma in one, anaplastic carcinoma in one, and adenocarcinoma in one. Non-TB pneumonia was documented in five patients and was associated with HIV-1 infection in four. Other causes of PE were congestive heart failure, decompensated cirrhosis, constrictive pericarditis, or undetermined; only one of these latter patients was HIV-seropositive. The authors therefore found TB to be the predominant cause of PE and it is strongly associated with HIV-1 infection. In an African area highly endemic for HIV-1 and Mycobacterium tuberculosis co-infection, PE should therefore be considered a good marker of TB as well as HIV-1 infection.
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PMID:Pleural effusion, tuberculosis and HIV-1 infection in Kigali, Rwanda. 844 20

Ninety-three evaluable patients with metastatic breast cancer previously treated with chemotherapy, received mitoxantrone as a single agent (14 mg/m2, by rapid intravenous infusion, once every 3 weeks). Patients received a median of 7 courses (range 2 to 18), with a mean cumulative total dose of 133 mg (range 36 to 342). A complete response (CR) was achieved in 2 patients (2%). Partial response (PR) was observed in 23 patients (25%). The overall response rate (CR+PR) was thus 27%, with a median duration of 9 months (range 3 to 18). Responses were observed in all metastatic sites, except for brain and peritoneum. Stabilization (S) occurred in 26 patients (28%). The remaining 42 patients (45%) showed clear progression of their metastatic disease while on therapy. The actuarial 24-month survival for the whole group was 13%, increasing to 29% in responders (CR+PR), as compared with only 10% for non-responders (S+P; P < 0.0001). Mitoxantrone was generally well tolerated; nausea, vomiting and hair loss were mild. Nine out of 625 treatment cycles resulted in leukopenic fever with uneventful recovery. All patients had serial MUGA scans; 3 patients (cumulative total doses of 200, 250 and 342 mg, respectively) developed a significant drop in the left ventricular ejection fraction. Clinical evidence of congestive heart failure was observed in one patient who had received prior doxorubicin-based adjuvant chemotherapy. Mitoxantrone seems to be as effective as other drugs given singly or in combination as second-line chemotherapy in patients with metastatic breast cancer. Its low morbidity makes its use attractive in this setting.
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PMID:Second-line chemotherapy with mitoxantrone as a single agent in metastatic breast cancer. 845 64


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