Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 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

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

We describe the case history of a 13 years old boy who developed osteogenic sarcoma of the left thigh, six years after diagnosis of osteogenesis imperfecta tarda with a positive family history. Only four other patients with this disease combination are reported in the literature. Preoperative treatment with high-dose Methotrexate caused marked tumor regression, as shown at examination of amputation material. The inter-relationships between the two disorders are discussed and the literature is briefly reviewed.
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PMID:Osteogenic sarcoma complicating osteogenesis imperfecta tarda. 27 54

Osteogenic sarcoma may be treated effectively by radical surgical removal of the primary tumor and combined chemotherapy, including Adriamycin and high dose Methotrexate. In order to render any protocol a safe procedure, strict precautions are required to avoid drug toxicity. We present a protocol, "COSS 77", presently employed in several university hospitals of West Germany and Austria. Final results concerning long term prognosis and long term side effects are not yet available.
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PMID:[Multidrug chemotherapy of osteogenic sarcoma (author's transl)]. 29 43

DNA metabolism in bone marrow cells was measured under high-dose Methotrexate/Leucovorin adjuvant chemotherapy of a patient with primary amputation of his right leg because of osteogenic sarcoma. The biochemical data showed that there was no rescue effect of Leucovorin after 200 mg/kg Methotrexate. Corresponding to this "biochemical failure" of the rescue effect the patient died from the complications of a long and very severe bone marrow suppression. To improve the safety of this therapeutic regimen the intravenous injection and in some cases a higher dose of Leucovorin is recommended.
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PMID:[High-dose methotrexate/leucovorin adjuvant chemotherapy of osteogenic sarcoma: biochemical effects in DNA-synthesis of bone marrow cells (author's transl)]. 30 51

The occurrence of overall toxicity was analyzed for 43 patients with osteosarcoma who received 349 high-dosage courses of methotrexate (HD-MTX) with citrovorum factor (Leukovorin) "rescue" (CF). The dosages of HD-MTX ranged from 50 to 350 mg/kg. Overall toxicity was assessed on the basis of five manifestations of toxicity: stomatitis, dermatitis, myelosuppression, liver dysfunction, and kidney function abnormalities. The great majority (91.4%) of the infusions were well tolerated, but 8.6% were associated with moderate or severe toxicity. Stomatitis and serum glutamic-oxaloacetic transaminase (SGOT) changes were the most frequent postinfusion findings. Three patients died from causes related to MTX toxicity. Dose, age, sex, and number of prior infusions were investigated by logistic regression analysis for prognostic effect on frequency of moderate to severe overall toxicity. Age and number of prior infusions had significant (P less than 0.06) effects on overall toxicity. Patients older than 15 years with greater than 10 prior infusions constituted the "high risk" group with a risk of moderate to severe toxicity 6.3 times that of the younger patients with fewer than 10 infusions.
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PMID:Evaluation of overall toxicity of high-dosage methotrexate regimens. 31 42

Methotrexate is now used widely for the treatment of acute leukemia, non-Hodgkin's lymphoma, osteogenic sarcoma, choriocarcinoma, breast carcinoma, pulmonary and epidermoid carcinoma, and intrathecal chemotherapy. It is also useful in bone marrow transplantation, severe psoriasis, rheumatoid arthritis, dermatomyositis, Wegener's granulomatosis and sarcoidosis. The recent dramatic intensification of methotrexate therapy can be attributed in part to advances in our understanding of the clinical pharmacology of the folate antagonists, as well as to the combination of positive results and their effective dissemination to medical oncologists. The review summarizes the pharmacologic findings and illustrates how they are currently being applied to the treatment of malignant disease.
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PMID:The clinical pharmacology of methotrexate: new applications of an old drug. 34 86

Methotrexate (MTX) has been implicated as a cause of interstitial pneumonitis and/or fibrosis, but the mechanism by which the drug causes these processes is not known. The purpose of this study was to determine whether patients receiving high-dose MTX developed a consistent decrease in pulmonary function, which would implicate a role for total dose of MTX received in the pathogenesis of the lung toxicity. Pulmonary function studies, including spirometry, plethysmography, and diffusing capacity at two levels of alveolar PO2, were performed in 38 adolescents treated for osteogenic sarcoma. The patients were divided into three groups including 12 patients (group 1) studied before and during therapy, 15 patients (group 2) studied during therapy, and 11 patients (group 3) studied after completion of treatment. While total dose received at the time of the study varied from 0 to 256 gm/sq m, pulmonary function showed no change, with one exception. A mild restrictive defect and decrease in diffusing capacity due to unilateral pleural and diaphragmatic disease, whose relationship to MTX therapy is uncertain, developed in one patient. MTX, when administered in high dose to young patients by the described protocol, causes no dose-related decrease in pulmonary function.
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PMID:Lung function in adolescents receiving high-dose methotrexate. 44 Aug 94

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

The development and application of the VCR-MTX-CF regimens for the treatment of osteogenic sarcoma have changed the biological behavior of the tumor. Recent results strongly project major advances for the future. Although the major effect of chemotherapy resides in the eradication of micrometastases, its application for treatment of the primary tumor may also be considered. However, careful experimental design and follow-up periods for several years will be required to determine the optimum approaches. For example, it is possible that the interaction between weekly VCR-MTX-CF and radiation therapy may assume increasing importance. Thus, with the effective application of VRC-MTX-CF, the management of osteogenic sarcoma has evolved into a multidisciplinary approach and future advances will be based on the collective judgement of specialists from many fields.
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PMID:Osteogenic sarcoma: state of the art with high-dose methotrexate treatment. 108 79


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