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)

Since January 1976 high-dose methotrexate (HDMTX) therapy has been used in the management of patients with osteogenic sarcoma at the Orthopaedic Department, University of Vienna. 7500 mg MTX/sqm body surface is administrated in a four-hour infusion with citrovorum factor rescue. This therapy is combined with dactinomycin, adriamycin, bleomycin, cyclophosphamide and vincristine in a multi-drug chemotherapeutic program as a prophylactic regimen after surgical treatment of the primary tumour, as well as in the management of metastases. So far, 12 patients have received a total of 46 infusions with HDMTX at montly intervals (6 patients already had widespread metastases). The use of several precautions such as adequate hydration 3 l/sqm body surface fluid), systematic alkalinization of the urine and regular control of the serum MTX level renders HDMTX therapy less hazardous. Five out of the 46 infusions were followed by mild toxic reactions consisting of mouth ulceration, fever and/or bone marrow depression. One out of the 6 patients with metastases and 5 out of the 6 patients receiving HDMTX as a prophylactic measure are without evidence of disease at present. In view of the short observation period, this report is limited to clinical observations only.
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PMID:[Clinical observations on the use of high-dose methotrexate treatment in osteogenic sarcoma (author's transl)]. 7 Aug 89

Since April 1974, 60 patients with squamous cell carcinoma of the head and neck region, of poor prognosis and generally in advanced stages, were treated with the combination of a cytotoxic regimen--VBM (Vincristine, Bleomycin and Methotrexate) and radical radiotherapy. The essential feature of the combination is the administration of pulses of VBM synchronous with a course of fractionated external radiotherapy in order to achieve potentiation of radiotherapy. On average 4-5 pulses of VBM were given during treatment, combined with radiotherapy on a Cobalt unit. The selection, preparation and management of the patients are described. Intense mucositis and intercurrent infection provide the main problems during treatment and close management is essential. Late complications have not been a serious problem. The crude actuarial survival rate at 24 months is 61%. The probability of survival without any recurrence to 24 months following initial treatment is 46%. Local control was achieved by the initial treatment in 43 patients. These results suggest that potentiation of radiotherapy and an increased therapeutic ratio has been obtained by the addition of VBM to radiotherapy and there is a possibility that the occurrence of distant metastases has been reduced or postponed.
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PMID:Synchronous VBM and radiotherapy in the treatment of squamous cell carcinoma of the head and neck. 7 3

Diethylnitrosamine (DEN) was applied orally to a total of 250 female Wistar rats in a single dose (d) of 3 mg/kg body weight 5 times a week for a duration of 20 weeks. After approximately 150 days exploratory laparotomy was performed to all animals. By inspection of the liver they were divided into 4 stages of disease according to the extent of cancer formation. The reaction of rats with DEN induced liver tumors was tested using a 4-drug combination chemotherapy with different equitoxic doses of Adriamycin (Adm), Methotrexate (Mtx), 5-Fluorouracil (5-FU) and Cyclophosphamide (CP). No benefit of drug treatment could be noted. In drug treated animals no decrease in the development of the liver tumors, in the frequency of metastases nor in the frequency of tumors of other origin could be demonstrated. The parallels of chemotherapy in chemically induced liver cancer to clinical experience are discussed.
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PMID:Chemotherapy studies in autochthonous rat tumors: hepatomas. 20 2

Metastases of osteosarcomas do not grow according to a simple exponential function, but rather according to a type of Gompertz' function where flattening with a tendency toward plateau formation sets in after a certain time. This deviation from an exponential growth type corresponds to a substantial increase in the initial tumor size--doubling time. The metastasis doubles in the period after its transfer faster than when it first becomes visible in an x-ray. Another important conclusion resulting from the use of the Gompertz model is the assumption of a tumor-specific maximum volume which cannot be exceeded over a period of infinite growth. For lung metastases of osteosarcoma this volume amounts to approximately 120 cm3. The critical volume which kills the host is, at 70 to 80 cm3, relatively close to this theoretical growth limit (only approximately one cell division below this limit). If a metastasis develops from a single cell, the number of divisions up to this point is approximately 46. Of these, 38 lie within the growth zone which is not visible via x-ray. Since cell-cycle specific agents (for example Vincristin and Methotrexate) have the greatest effect against rapidly proliferating tumors, these drugs (for example alkylantic drugs) are especially effective in the case of slowly proliferating neoplasms. Therefore, use of these drugs should be favored when the metastasis is visible in the x-ray. Since occasionally, particular when the primary tumor is still relatively small, metastasization may not necessarily have already taken place, radical operation of the primary tumor should be carried out as soon as possible. A preliminary irradiation of the primary tumor cannot prevent metastasization with certainty. Therefore delayed amputation should be avoided.
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PMID:[On the growth characteristics of human osseous sarcoma metastases: mathematical calculations and clinical consequences (author's transl)]. 27 86

Methotrexate (MTX) covalently bound to bovine serum albumin (MTX-BSA), injected ip (10 mg/kg) once every 4 days for a total of 4 doses, was more effective than an equivalent dose of free MTX in reducing the number of metastases observed in female (C57BL/6 X DBA/2)F1 mice bearing the sc implanted Lewis lung carcinoma. Treatment with the high-molecular-weight derivative of MTX in addition caused a decreased rate of growth of the primary tumor and a modest increase in the life-span of the tumor-bearing animal. When tumor-bearing mice were killed after receiving injections of [3H]MTX or [3H]MTX-BSA, no difference in the amount of drug was found at the tumor site after 1 hour; however, after 8 or 24 hours, twice as much radioactivity was found in the tumors of mice treated with carrier-bound drug. Analysis of this radioactivity indicated a ratio of 60--80% carrier-bound to 20--40% free MTX.
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PMID:Control of solid tumor metastases with a high-molecular-weight derivative of methotrexate. 28 78

Vincristine-high-dose methotrexate-citrovorum factor (VCR-MTX-CF) was administered preoperatively at weekly intervals to eight patients, four with primary tumors and four with pulmonary metastases. These patients had not received prior VCR-MTX-CF treatment. A similar treatment program was administered to five patients with pulmonary metastases who had received prior VCR-MTX-CF. Among the eight patients who had not received prior VCR-MTX-CF, complete responses were obtained in three with primary tumors (this was followed by surgical excision) and two with pulmonary metastases. Partial responses occurred in two additional patients. Partial responses were also obtained in two patients who had received VCR-MTX-CF. Chemotherapy and surgery in one patient with an extremity lesion resulted in preservation of the limb and useful function. The major toxicity was anorexia and weight loss. Other side effects included stomatitis, myelosuppression, hepatitis and transient renal impairment. The weekly program was highly effective when compared to responses obtained with the tri-weekly schedule utilized in previous studies.
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PMID:Weekly high-dose methotrexate-citrovorum factor in osteogenic sarcoma: pre-surgical treatment of primary tumor and of overt pulmonary metastases. 29 28

Five dogs with ostoegenic sarcoma were treated by surgical removal of the primary tumor and by adjuvant chemotherapy. Methotrexate at dosages of 3 to 6 g/m2 was used with leucovorin rescue. All dogs tolerated E g of methotrexate/m2 of body surface, but granulocytopenia precluded escalation beyond this dosage in 4 dogs. The rate and time of appearance of pulmonary metastases were not altered by treatment, with all dogs developing metastases at a median time of 4 months after amputation.
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PMID:High-dose methotrexate and leucovorin rescue in dogs with osteogenic sarcoma. 31 44

A randomized trial comparing Vincristine, Adriamycin, Cyclophosphamide (VAC) with or without Methotrexate with citrovorum factor rescue (VACM) was performed in 64 patients with metastatic postmenopausal mammary carcinoma. Previous treatment of metastases, dominant site of metastases and performance condition were similar in the patients. No significant difference was found in the response rates (complete remission + partial remission; VAC 21/31, VACM 25/33), in the duration of the remissions or in the survivals. The duration of remission in CR was significantly longer than in PR. No serious side effects were observed. The VAC regimen is preferable, particularly with respect to the costs and the simple procedure of administration.
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PMID:Combination chemotherapy in advanced postmenopausal mammary carcinoma. A comparison between VAC and VACM therapy. 39 76

Recent advances in the use of chemotherapy for treatment of osteosarcoma have altered out pessimism in this disease. Results are presented from 3 groups of investigators using different agents as adjuvant chemotherapy following immediately upon amputation of the primary. The Roswell Park Memorial Institute began a regime, immediately after amputation, of adriamycin 30 mg/M2 for 3 doses and given every 4-6 weeks. This study was subsequently expanded in a cooperative group (ALGB) and the results on 20 patients analyzed. At 19 months approximately 75 per cent are free of any pulmonary metastases compared with 10-25 per cent expected from amputation alone. Similar results have been obtained by other Centers using different chemotherapeutic agents. In Boston Children's Hospital high dose Methotrexate with citrovorum factor is used. In 12 of these patients local control of the primary by surgery was obtained and of these only 1 developed pulmonary metastases during an observation time of 23 months. At the M. D. Anderson Hospital multi-drug combinations were used including Cyclophosphamide, Vincristine, L-Phenylalamine Mustard and Adriamycin. They reported a survival rate of 55 per cent (10 out of 18). All of these neoplastic agents have toxic side effects but when carefully used these effects are minimized and the quality of life is quite good. Many questions must be answered by future controlled long term follow-up studies.
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PMID:Chemotherapy of osteosarcoma. 105 62

92 squamous cell carcinomas of the supraglottic larynx classified as T3 were treated from 1977 through 1987 and retrospectively analyzed. All the patients of this series received chemotherapy as initial treatment (2 cycles). From 1977 through 1981 the combination of Vincristine-Methotrexate-Bleomycin (VMB) was employed; after 1981, the protocol: Cisplatinum-5 FU with or without Bleomycin (CF) was administered instead of VMB. All the patients were then surgically treated on the tumoral site and cervical lymph chains. At 5-year, there was no significative difference between the two chemotherapeutic regimen in term of locoregional recurrences and second primaries. 5-year actuarial survival rate was higher for patients treated with the CF protocol (71%) versus (54%) with the VMB regimen. Systemic metastases occurred less frequently after CF (4.5%) than after VMB (22.4%). These findings suggest that chemotherapy has substantially some activity against microscopic distant metastases.
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PMID:[Adjuvant chemotherapy in supraglottic epidermoid carcinoma stage T3]. 129 74


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