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)

Tumour associated monoclonal antibodies (MAbs) HMFG1, HMFG2 and H17E2, labelled with 123iodine or 111indium, were used to detect primary and metastatic cancer by external body scintigraphy in patients with ovarian, breast and non-small cell lung cancer (NSCC). Successful localisation was seen in all patients with primary and 80% of the metastatic NSCC, 50% of primary and 70% of metastatic breast cancer lesions and in 80% of patients with metastatic ovarian cancer. On the other hand, imaging carried with a radiolabelled non-specific MAb produced positive results in 3 out of 5 cases with primary NSCC. Therefore, non-specific imaging should be further studied in clinical research for the evaluation of the specificity of radioimmunodetection. A therapeutic procedure which has shown promise is that of intracavity administration of radiolabelled antibodies. Twenty-nine patients with resistant ovarian cancer have been treated with intraperitoneal 131I-labelled MAbs (HMFG1, HMFG2, AUA1, H17E2). There were no significant responses in 8 patients with gross disease. There were 2 responses in 15 assessable patients with tumour nodules of less than 2 cm in diameter. Out of 6 patients with microscopic disease, 4 are disease-free with follow-up time of 6-40 months (mean = 17.5 months).
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PMID:Antibody-guided diagnosis and therapy of malignant lesions. 316 48

We have treated 33 patients with different types of advanced cancer by 10-day continuous i.v. infusion courses of hexamethylene bisacetamide (HMBA), a drug that produces differentiation of a variety of transformed cell lines on prolonged exposure in vitro to drug concentrations of 3 to 5 mM. In this dose-finding and pharmacokinetic study, five dosage levels were explored from 12 to 28 g/m2/day. Patients who had not shown progression of disease were given repeat courses of therapy at 28-day intervals. Seventy-two courses of therapy were administered; 17 patients received one course; eight patients received two; six patients received three; and one patient each received four and 17+ courses, respectively. The maximal tolerated dose was 28 g/m2/day for 10 days; the dose-limiting toxic effects were thrombocytopenia with hemorrhage and central nervous system dysfunction manifesting as disorientation and confusion. Based on these studies the recommended dosage for Phase II studies by the 10-day schedule is 24 g/m2/day. Pharmacokinetic studies demonstrated rapid clearance of HMBA from plasma; the decay phase data fit a one compartment model with a mean plasma half-life of 2.5 h and a range from 0.6 to 5.8 h. Mean plasma steady-state levels in our patients were 0.37, 0.58, 0.86, 0.88, and 1.42 mM, at the 12-, 16-, 20-, 24-, and 28-g/m2/day dosage levels, respectively. The data indicate that plasma HMBA concentrations of 1 mM can be maintained for 10 days with acceptable patient tolerance, but that HMBA concentrations in excess of 1.4 mM for 10 days are associated with substantial hematological and central nervous system toxicity. Objective antitumor effects were observed in five patients; one woman with non-small cell lung cancer, who has received 17+ courses over a period of 28+ mo, achieved a partial remission that continues at 28+ mo on therapy. Transient regression of cutaneous metastases was observed in three patients with breast carcinoma and one patient with colorectal carcinoma.
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PMID:Phase I trial and clinical pharmacological evaluation of hexamethylene bisacetamide administration by ten-day continuous intravenous infusion at twenty-eight-day intervals. 319 1

Forty-five patients with advanced non-small cell lung cancer (NSCLC), with progressive inoperable tumors were treated. Twenty-three patients were of "limited" stage. Six patients had received previous thoracic radiotherapy. Patients with central nervous system (CNS) metastases, Karnofsky scores of less than 30 or more than 70, and patients over 70 years of age were excluded from the study. Cyclophosphamide (2.5 g/m2) was infused intravenously over 3 hours with the same Mesna dose. At the midpoint of the infusion, 3.5 g/m2 infosfamide was delivered as a bolus. Additional Mesna was administered over the next 8 hours. A maximum of four courses were given at three weekly intervals. One-hundred-thirty-eight courses were administered and 53% of patients completed all four treatments. The response rate was 38%, with three (7%) complete responses. Seven additional patients (15%) with stable disease symptomatically improved by two steps or more on the Karnofsky scale at the end of treatment. Median survival for all 45 patients was 7 months, range less than 1 to 25 months. Sixteen courses were complicated by Grade 3 thrombocytopaenia and/or leukopenia (Grade 4 on six occasions, Grade 3 on seven occasions) on the blood count taken immediately before chemotherapy. Intravenous antibiotics were required on 14% of the total number of courses; and three patients died of probable treatment related causes. Two episodes of severe ifosfamide encephalopathy occurred but recovery was complete, and four episodes of frank hematuria also occurred. The Karnofsky score was more than 70 in 33% of patients one month after the end of chemotherapy compared with 0% before treatment. Unlike many chemotherapeutic regimens for NSCLC, double alkylating agent treatment with ifosfamide and cyclophosphamide improved the performance status without major toxicity in a selected patient population. The overall survival, however, remains short and further alkylating agent combinations need to be considered in the future.
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PMID:Double alkylating agent therapy with ifosfamide and cyclophosphamide for advanced non-small cell lung cancer. From the Manchester Lung Tumour Group. 333 40

CT staging of mediastinal lymph node metastases from bronchogenic carcinoma is a subject of considerable controversy. The frequency of metastases to normal-sized lymph nodes is a critical issue related to the sensitivity of CT. The authors prospectively examined 42 patients with bronchogenic carcinoma with CT; in 39, careful surgical-pathologic correlation of mediastinal lymph node status was possible. Only 7% had metastases limited to mediastinal lymph nodes that were normal-sized at CT. This reflected a low overall frequency of metastases to normal-sized nodes and several diagnostic factors that converted potentially false-negative studies into true-positive CT studies. In this small series, metastases to enlarged nodes were more likely to have extracapsular spread of tumor, a poor prognostic factor. Overall, the authors do not consider metastases to normal-sized mediastinal lymph nodes to be a major problem in CT staging of non-small cell lung cancer.
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PMID:Bronchogenic carcinoma metastatic to normal-sized lymph nodes: frequency and significance. 333 4

Between 1976 and 1984, 242 patients with presumably operable lung cancer were treated surgically. In the Canisius Wilhelmina Hospital, Nijmegen, The Netherlands, in the period 1976 to 1980, 109 of 131 (83.2%) patients underwent cervical mediastinoscopy to assess operability. They were studied retrospectively. During this examination, lymph node metastasis was demonstrated in three of 19 (15.8%) patients with left upper lobe lung cancer. At thoracotomy after a normal cervical mediastinoscopic study or no mediastinoscopic study, periaortic lymph node metastases were found in eight of 34 (23.5%) patients with left upper lobe lung cancer. In the period 1981 to 1984, the value of left parasternal mediastinoscopy was studied prospectively in patients with left lung cancer in the Canisius Wilhelmina Hospital, Nijmegen; in the Lung Centre of the Radboud University Hospital, Nijmegen; and in the Lung Center of the Dekkerswald Medical Centre, Groesbeek. Cervical or cervical and parasternal mediastinoscopy were performed in 69 of 111 (62.2%) patients. At parasternal mediastinoscopy performed after a normal cervical mediastinoscopic study, periaortic lymph node metastases were found in seven of 31 (22.6%) patients with left upper lobe lung cancer. All periaortic lymph node metastases showed intranodal and extranodal growth. The resectability rate in left upper lobe lung cancer was 79.4% in the retrospective group and 96.5% in the prospective group. There were no serious complications after parasternal mediastinoscopy. These data point to the reliability of parasternal mediastinoscopy in the assessment of left upper lobe lung cancer. The study provides essential information for the staging and treatment of non-small cell lung cancer of the left upper lobe.
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PMID:Parasternal mediastinoscopy. Assessment of operability in left upper lobe lung cancer: a prospective analysis. 333 96

10-Ethyl-10-deazaaminopterin (10-EDAM) is an analogue of methotrexate with improved preclinical anticancer activity, more selective entry, and greater conversion to polyglutamate forms in neoplastic cells. In this Phase I trial, we have treated 62 adults with advanced solid tumors, giving 10-EDAM i.v. on either a weekly x 3 schedule (35 patients) or a weekly schedule (27 patients). The dosage levels ranged from 5 to 120 mg/m2. The toxicity observed with 10-EDAM was qualitatively similar to that of methotrexate. Oral mucositis was the dose-limiting toxicity; diarrhea, skin rash, leukopenia, thrombocytopenia, and mild elevations of serum glutamic-oxaloacetic transaminase, prothrombin, and partial thromboplastin times were also observed, but were not dose limiting. A weekly dosage of 80 mg/m2 with escalation or attenuation in accordance with patient tolerance, or 100 mg/m2 weekly for 3 weeks, followed by a 2-week "rest period" are recommended for Phase II assessment. 10-EDAM produced partial remissions in three patients with non-small cell lung cancer and one patient with breast cancer lasting 6, 40+, 26+, and 15 months, respectively. Pharmacokinetic studies carried out at the 5, 30, and 100 mg/m2 dosage levels demonstrated the drug to have a triphasic disappearance from plasma. Elimination was independent of dose over the range tested, with mean plasma half-lives of: alpha = 12.9 min, beta = 1.5 h, and gamma = 11.9 h. Cumulative urinary excretion of the drug ranged from 13 to 55% of the administered dose (mean = 33%); 88% of the urinary drug appeared within the first 4 h following drug administration. The pharmacokinetic behavior of the first and second weekly dosages were consistent within a given patient. The metabolites 7-hydroxy-10-EDAM, and 10-ethyl-10-deaza-2,4-diamino-pteroic acid were demonstrated in the plasma and urine of treated patients. In studies of tissue homogenates from two patients with skin metastases, more extensive retention of the drug and of its polyglutamates was observed in the breast cancer metastases than in the metastases from a kidney cancer or in normal skin.
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PMID:Phase I trial and clinical pharmacological evaluation of 10-ethyl-10-deazaaminopterin in adult patients with advanced cancer. 341 10

Despite improved resolution with new imaging techniques, surgical confirmation of mediastinal lymph node status is often required for reliable staging of patients with non-small cell lung cancer. Recent scintigraphic studies suggest that s.c. administration of radiolabeled antibodies can be more efficient than the i.v. route for targeting regional lymph nodes in animals and humans. To determine if this approach could be applied to the lymphatics of the lung, we injected both specific and irrelevant radiolabeled monoclonal antibodies via a flexible fiberoptic bronchoscope through the mucosa of lobar bronchi in normal dogs. The injected antibodies were expected to drain by way of local lymphatic vessels toward the central lymph nodes, in effect following the same pathway as do cells metastasizing to these nodes during early regional tumor dissemination. To accomplish this, anesthetized dogs were intubated and then coinjected with the two labeled antibodies [600 microCi/100 micrograms (total)] through a fiberoptic bronchoscope. The animals were serially imaged and then autopsied 14-36 h after injection. Individual hilar and carinal nodes contained over 1% of the injected 131I-labeled specific antibody dose and the average selectivity was 2.5:1 with respect to a coinjected irrelevant IgG. Distant organs (mesenteric lymph node, liver, spleen, bone marrow, and lung parenchyma other than the injection site) contained much less radioactivity, and those sites accumulated a greater fraction of the non-specific labeled antibody. The ratio of iodine-131 to iodine-125 counts between hilar/carinal lymph nodes and abdominal lymph nodes ranged from 15:1 to 100:1. These initial studies indicate efficient delivery of antibody to a subset of the regional nodes via pulmonary lymphatics. They suggest the feasibility of this technique which may be of use in the detection and perhaps therapy of human lung cancer metastases in regional lymph nodes.
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PMID:Immunolymphoscintigraphy of pulmonary and mediastinal lymph nodes in dogs: a new approach to lung cancer imaging. 347 55

Nonsurgical combined approaches of non-small cell lung cancer represent a concept that has only been investigated so far with chemotherapy and radiation therapy. Thoracic irradiation of locoregional disease is associated with a high rate of local control and a 5-10% long-term (5-year) survival; however, distant metastases remain the main cause of failure. This observation suggests that the tumor is often microscopically disseminated at the time of diagnosis. Systemic therapy therefore must be associated to radiation therapy to try to control both the undetectable metastases and the local disease. However, the results reported so far have been disappointing, probably because of the modest activity of the available chemotherapy. Further progress with the combined approach requires new developments in the chemotherapy of non-small cell lung cancer, particularly the introduction of new active drugs.
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PMID:Nonsurgical combined modality therapies in non-small cell lung cancer. 351 76

The International Staging System for Lung Cancer provides for classification of six levels of disease extent in five stage groups that relate to patient management and prognosis. Stage 0 is reserved for patients with carcinoma in situ. The Stage I and II definitions provide for classification of two levels of disease extent completely contained within the lung that have different prognostic and therapeutic implications. Definitive resection is the first choice of therapy for patients with non-small cell lung cancer in these stage groups. The Stage II category takes into account the erosion of survival expectations in the optimum group of T1 and T2 patients as a consequence of intrapulmonary lymph node involvement. Although small cell carcinoma is infrequently encountered as Stage I and Stage II disease, these classifications may be useful in the structure of investigational programs involving adjuvant surgery. The exclusion of distant metastases and the division of Stage III into two levels of extrapulmonary disease allow for selection of patients for specific treatment plans. Patients with non-small cell tumors with Stage IIIa disease usually are candidates for definitive surgical treatment. The specificity of the T and N definitions in the Stage IIIa and IIIb categories identifies patients for whom particular radiotherapy treatment plans are structured and protocol assignments are made. It is consistent with patient management concepts that all those with distant metastases are classified as having Stage IV disease. Implications of the system for selection of surgical, radiotherapeutic, and chemotherapeutic regimens are rational for all cell types. The classification meets the requirement for simplicity and can be readily applied in a broad spectrum of clinical and teaching environments. It is, however, sufficiently specific to be useful for reporting results of investigational therapies. Prospective use of the classification should encourage precision in clinical evaluations that exploit full use of refinements in imaging technologies. The cooperative efforts of the Task Force on Lung of the AJCC and the TNM Committees of the UICC to bring this classification system to fruition and international acceptance have been described. It has been adopted by these groups and others, including the International Association for the Study of Lung Cancer, the Japanese Cancer Committee, and the Spanish Society of Respiratory Disease, as their official recommendation for staging lung cancer.
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PMID:The new International Staging System for Lung Cancer. 362 29

The irradiation of radical resectable lung cancer is unambiguously not as effectively as surgery, and also the preoperative radiation with high tumour doses has not demonstrated any benefit in survival rates. Tumours of the superior sulcus could be an exception in both treatment modalities. As shown in randomized studies one could suggest some advantage employing postoperative irradiation of patients especially with mediastinal node metastases. The addition of chemotherapy to high dose irradiation with curative intent in inoperable non-small cell lung cancer has not been shown to increase survival. The combined chemo-radiotherapy of small cell lung cancer significantly reduced the incidence of relapse and prolonged the disease free interval but did not affect long-term survival.
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PMID:[Therapy of bronchial carcinoma from the radiotherapist's viewpoint]. 609 81


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