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)

Fotemustine is a new chloronitrosourea recently developed by the French company Servier. It is chemically characterized by the graft of an aminophosphonic acid on the chloronitrosourea radical, which makes it highly lipophil. The preclinical studies revealed a lower mutagenicity and hepatotoxicity when compared to BCNU. The pharmacokinetic studies showed a high body clearance and a short half-life. The phase I study enabled us to determine the definitive treatment schedule: 100 mg/m2/week during 3-4 consecutive weeks followed by 5 weeks' rest and a maintenance therapy of 100 mg/m2 every 3 weeks for stabilized or responding patients. Fotemustine should be given as a 1-h intravenous infusion, protected from daylight. There was no life-threatening toxicity and positive activity was observed in different tumors and especially melanomas. This indication was thus chosen for the phase II study. Among the 153 evaluable patients, the response rate reached 24.2%. It depended on the location of the metastatic sites, with 25% brain metastases, 19.2% visceral metastases, 8.8% liver metastases and 31.8% skin and lymph node metastases. The median duration of response was 22 weeks. The median overall survival of responding patients reached 85 weeks, while it dropped to 52 weeks in case of minor response or stabilization and 17 weeks in case of progression. The hematological toxicity was moderate (WHO grade III and IV: 46.3% leukopenia and 40.3% thrombopenia) and delayed as for other nitrosoureas (nadir: white blood cells: day 44 and thrombocytes: day 35).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Fotemustine, a new nitrosourea derivative. Current status of development]. 218 26

A group of 110 patients (68 male and 42 female) with cerebral metastases, treated at the Institute of Clinical Oncology and Radiotherapy, Zagreb University School of Medicine, during the period 1978-1984, were included in the study. Most patients were aged 50-60 years. Out of 110 patients, 52 were treated by radiotherapy and 58 by radiotherapy plus chemotherapy. Metastases from the bronchus carcinoma, breast carcinoma, melanoma and gastrointestinal carcinoma were present in 59%, 21.8% and 4.6% of patients, respectively. In 1.8% metastases from hypernephroma and in 3.6% from other malignant tumors were observed. In 4.6% cases, the origin of metastases could not be identified. Fifty-two out of 110 patients were treated by radiotherapy alone. They received 3000 cGy in 8-10 fractions, to the whole brain, with two parallel opposed fields. Fifty-eight out of 110 patients treated with radiotherapy and chemotherapy were given the same radiotherapeutic treatment. Chemotherapeutically, they were treated with BCNU and CCNU with or without Vincristin in standard doses. In the group of 52 patients treated by radiotherapy alone the median survival was six months (1-16 months), i.e. the same as in the group treated by both radiotherapy and chemotherapy (1-26 months).
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PMID:The influence of radiotherapy and chemotherapy on cerebral metastases. 226 13

Pyrazine diazohydroxide (sodium salt, NSC 361456; PZDH) is a new antitumor drug with relatively broad activity in initial evaluations against murine leukemias, solid tumors, and two human tumor xenografts in vivo. The present studies were designed to address questions about PZDH activity on different treatment schedules, its activity against metastases, and the extent of its cross-resistance with established drugs. Human LOX amelanotic melanoma xenografts in athymic mice were used to explore schedule dependence and activity against natural metastases, and a series of drug-resistant murine leukemias provided an in vivo cross-resistance profile. Single-dose treatment and prolonged treatment provided equivalent therapeutic responses to PZDH by both the i.p. and i.v. routes in the i.p. LOX model. A s.c. LOX model resulting in spontaneous pulmonary metastases was adapted for bioassay and quantitation of the numbers of LOX cells killed by PZDH among both primary and metastatic cell populations. It was demonstrated that PZDH afforded about 2-log10 orders of magnitude greater cell kill among pulmonary metastases than against primary s.c. LOX tumors in the same mouse. Murine leukemias resistant to doxorubicin (ADR), vincristine (VCR), cisplatin (DDPt), methotrexate (MTX), N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU), and cyclophosphamide (CPA) were not cross-resistant to PZDH. However, both P388 and L1210 leukemia sublines resistant to melphalan (L-PAM) were cross-resistant to PZDH, suggesting that patients previously treated with L-PAM might have less likelihood of response to PZDH than those who had had no opportunity to develop L-PAM resistance. Although these observations should not be applied to clinical studies without due caution, they support clinical evaluation of PZDH as well as continued investigation of its molecular pharmacology.
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PMID:Schedule dependence, activity against natural metastases, and cross-resistance of pyrazine diazohydroxide (sodium salt, NSC 361456) in preclinical models in vivo. 231 Nov 70

Human malignant gliomas are karyotypically heterogeneous, composed of many cellular populations and isolated cell types identifiable by cytogenetic techniques. The distributions of cell types vary in high grade tumors. Some tumors are primarily near-diploid (35-57 chromosomes per cell), while others are hyperdiploid with chromosome numbers ranging from 58 to several hundred chromosomes per cell. Regional studies of several tumors suggest that the heterogeneity is not random. Anatomically different regions result from the combination of cellular distribution and their evolution over time. The karyotypic pattern of gliomas also reflects the tumor's evolution from a relatively homogeneous population of near-diploid cells to the hyperdiploid tumor that is removed by the neurosurgeon. The in vitro studies also suggest that there are phenotypic correlates to the karyotypic pattern of the tumor cells. Hyperdiploid cells are unstable in culture, tend to grow rapidly with short doubling times, and are often sensitive to such chemotherapeutic agents as BCNU. In contrast, the near-diploid cells are more normal in appearance, are stable in culture, grow slowly with long doubling times, are more likely to be resistant to the nitrosoureas and ultimately are the 'stem' cells that repopulate the tumor mass.
Cancer Metastasis Rev 1985
PMID:The subpopulations and isolated cell types of freshly resected high grade human gliomas: their influence on the tumor's evolution in vivo and behavior and therapy in vitro. 299 Jun 70

The effect of treatment with the hypoxic cell radiosensitizer misonidazole (MISO) and the radioprotector diethyldithiocarbamate (DDC) on the formation of spontaneous lung metastases of four different spontaneously metastasizing murine tumors was investigated. The tumors were mammary carcinoma MCA-K, hepatocarcinoma HCA-1, and sarcomas SA-4020 and SA-NH. Multiple daily treatments with MISO significantly enhanced the incidence of metastases only in MCA-K. Because only MCA-K, but not the three remaining tumors, is immunogenic, the treatment with MISO may be associated with the promotion of metastasis primarily in the immunogenic tumors. Treatment of mice with DDC had no influence on metastatic spread. However, when given prior to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), DDC reduced BCNU-induced enhancement of HCA-1 metastases.
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PMID:Effect of the radiosensitizer misonidazole and the radioprotector diethyldithiocarbamate on spontaneous metastasis formation of murine tumors. 301 3

Twenty-six adults, ages 27 to 60, with refractory metastatic solid tumors were treated with high-dose cyclophosphamide (Cy) + carmustine (BCNU) at one of three escalating dose schedules followed by autologous bone marrow transplantation (ABMT). Toxicity was severe and dose-related, with the maximum tolerated dose for the combination determined to be Cy 160 mg/kg and BCNU 900 mg/m2. Median time to WBC recovery (greater than or equal to 1,000/microL) was 13 days post-ABMT (range, nine to 22 days) and to a platelet count of greater than or equal to 50,000/microL, 22 days (range, 13 to 83 days). Sixteen of 20 evaluable patients (80%) responded to therapy with at least 50% reduction in measurable tumor, and three patients achieved complete remission (CR). Responders included eight of nine evaluable patients with breast carcinoma, two of five with melanoma, two of two with sarcoma, and four of four with colon carcinoma. Response durations were short (median, 4 months), even for complete responders, and relapses generally occurred at sites of previous metastases. In order for this approach to have a more significant impact on overall survival, it may need to be applied earlier in the natural history of the malignancy.
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PMID:High-dose combination alkylating agent therapy with autologous bone marrow rescue for refractory solid tumors. 304 66

The activity of the novel anticancer agent diethyl 1-3-(chloroethyl)-3-nitrosoureido ethyl phosphonate (S10036) was investigated on several rodent tumors. S10036 showed a good efficacy, comparable to that of the anticancer agent BCNU, against i.p transplanted P388 and L1210 leukemias. S10036 was very effective against the primary tumor and metastases of i.m transplanted M5076 reticular cell sarcoma of the mouse and against subline A of the Walker carcinoma of the rat. It was inactive against rodent tumors resistant to BCNU such as L1210/BCNU, ICIG-Ci4 murine fibrosarcoma and the Walker carcinoma subline B in the rat.
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PMID:Antitumor activity of the novel nitrosourea S10036 in rodent tumors. 306 16

Treatment of patients with hepatic metastases from colorectal cancer using hepatic artery floxuridine (FUDR) has been reported to induce high partial remission rates and perhaps prolonged survival. However, several investigators, including our own group, have obtained response rates of only 30%. Alkylating agents can increase the efficacy of antimetabolites. Based on clinical data and pharmacokinetic considerations the authors have combined FUDR with mitomycin C and carmustine (BCNU) by the arterial route. Thirty-six patients with hepatic metastases from colorectal cancer received FUDR 0.3 mg/kg/day 2 weeks of 4, mitomycin C 15 mg/M2 over 1 hour every 8 weeks, and BCNU 150 mg/M2 over 1 hour every 8 weeks--all via the hepatic artery using Infusaid pumps (Infusaid, Sharon, MA). The mitomycin C and BCNU were alternated monthly at the start of each FUDR cycle. The patient characteristics were as follows: 78% hepatomegaly, 44% also extrahepatic tumor, 42% prior systemic 5-fluorouracil. Combined partial and complete response rates were independent of prior chemotherapy: 71% if untreated, 67% with prior 5-fluorouracil. Median survival for the combined response/stable disease group was 13.7 months from the start of hepatic artery chemotherapy, and 4.5 months for the six nonresponders. Based on these data the authors have begun a randomized trial comparing single-agent FUDR to the FUDR, mitomycin C, BCNU combination.
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PMID:Treatment of metastatic colorectal cancer with hepatic artery combination chemotherapy. 308 Feb 21

A 41 year old male presented with headache, lethargy, and ataxia and found to have a left temporal lobe mass and a leukoerythroblastic peripheral blood smear. The latter prompted an iliac crest bone marrow biopsy on which a diagnosis of metastatic glioma was made and verified by immunohistologic characterization. The patient was treated with cranial irradiation and simultaneous systemic BCNU (bis-dichloroethylnitrosurea) with complete response. This case with diffuse bone marrow involvement demonstrates that a glioblastoma is capable of extracranial metastases without previous intervention. From a review of reported cases of gliomas of extraneural metastasis, it is concluded that untreated gliomas are capable of vascular spread although less frequently than previously manipulated tumors.
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PMID:Intracranial astrocytoma with diffuse bone marrow metastasis: a case report and review of the literature. 329 52

Three patients with malignant gliomas who developed dissemination of tumor at the time of recurrence are presented. All three patients received combination therapy including conventional radiotherapy and interstitial radiation therapy followed by systemic BCNU chemotherapy. A review of the literature on the development of glioma metastases and an analysis of the possible mechanisms of this uncommon growth pattern are presented.
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PMID:Patterns of recurrence in glioma patients after interstitial irradiation and chemotherapy: report of three cases. 336 13


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