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)

The rationale of preoperative chemotherapy for osteosarcoma requires: eradication of microscopic metastatic foci which have already occurred in many patients with osteosarcoma, determination of a more effective form of postoperative adjuvant chemotherapy and easier and safer limb-salvage procedures through clearer marginal definition with reduction of primary lesions. In this paper, chemotherapeutic effects on the 5-year survival rate were analyzed for 49 patients with primary non-metastatic osteosarcoma of the extremities treated with radical surgery. The efficacy of preoperative chemotherapy was assessed in 11 cases of osteosarcomas treated with systemic chemotherapy as a preliminary study. As to the 5-year cumulative survival rate, the systemic group (20 cases) showed a level of 56.7%, which was significantly higher (p less than 0.05) than the figure of 13.8% in a historical retrospective group (29 cases). In assessing the effective tumor response to preoperative chemotherapy, a close correlation between the tumor necrotic ratio and the ratio of decrease of serum alkaline phosphatase was revealed. Seven (63.6%) of 11 cases showed correlation of the tumor necrotic ratio with the ratio of decrease of serum alkaline phosphatase. The tumor necrotic ratios calculated were relatively definite (50-60%) in the CDDP group (3 cases), varied (10-70%) in the HDMTX group (4 cases), and low (less than 40%) in the ADR group (4 cases), regarded as a control group in further studies.
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PMID:[Rationale of preoperative chemotherapy of osteosarcoma]. 347 75

"Neo-adjuvant therapy" with preoperative high-dose methotrexate (HD-MTX) and CF rescue therapy was investigated in four children with osteogenic sarcoma. Immediately after the diagnosis of osteogenic sarcoma from biopsy, the patients were treated with three to five courses of weekly HD-MTX (300 mg/kg) with CF rescue. Three patients had en bloc tumor resection and one patient underwent disarticulation of the hip joint after the pre-operative HD-MTX. The effect of HD-MTX was evaluated on the basis of pathological changes between the specimen of the primary tumor taken at biopsy and that during surgery. Two out of four patients showed marked tumor cell reduction (greater than 50%) of the specimen upon surgery. Two patients who responded to the preoperative HD-MTX were further treated with HD-MTX on a post-operative adjuvant therapy basis for 18 months. Both of these patients survived with no evidence of disease for 35.6+ and 20.9+ months. Two patients who responded poorly to HD-MTX were treated with a multi-drug postoperative adjuvant therapy including cis-platinum, adriamycin, cyclophosphamide, actinomycin D, and bleomycin. One patient had a solitary lung metastasis at 12.2 months after amputation. Wedge resection of the metastatic tumor was performed and adjuvant therapy with cis-platimum has been given for 20 months. He has remained with no evidence of disease for more than 30 months. Another patient has been receiving multi-drug neo-adjuvant therapy without any evidence of disease for 11.9 months after surgery. These data suggest that neo-adjuvant chemotherapy based on the response to preoperative HD-MTX is more useful for increasing the cure rate of childhood osteogenic sarcoma.
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PMID:[Neo-adjuvant therapy in childhood osteogenic sarcoma: a pilot study of selective postoperative chemotherapy based on response to preoperative high-dose methotrexate]. 348 34

During the use of a therapeutic regimen of high-dose methotrexate (HD-MTX) with leucovorin rescue in two cases of osteogenic sarcoma and malignant lymphoma without central nervous system (CNS) involvement, serial EEG monitoring before and after MTX infusion was performed with special reference to occipital basic activity. The EEGs were analyzed as to the power average spectrum using an ATAC-450 (NIHON KOHDEN). At 48 hours after the initiation of MTX, there was a transient but statistically significant slowing, such as a drop in the dominant frequency and a decrease in the alpha/theta ratio. Complete recovery of EEG changes occurred within one week. No clinical symptoms suggestive of CNS impairment were noted in either case. These data suggest that EEG alterations might be a reflection of subclinical CNS impairment. Therefore, serial EEGs might be a good early indicator for the detection of leukoencephalopathy in high-risk patients.
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PMID:[Spectral EEG analysis in children treated with high-dose methotrexate]. 349 31

Adjuvant chemotherapy comprising Adriamycin (ADM) and Methotrexate (MTX) with Citrovorum Factor (CF) was administered on a randomization basis to 2 groups of patients with osteosarcoma after surgical ablation of the primary tumor. One group received high dose MTX (regimen I) and the other moderate dose MTX (regimen II). In both groups a short period of heparin treatment was also administered to prevent neoplastic emboli during surgery. All patients were free of metastasis at the beginning of therapy. The efficacy of therapy was determined by recording the percentage of continuously disease-free patients. This was compared to the disease-free survival in 132 patients previously treated with other ADM or ADM-MTX regimens and to a group of 39 patients treated during this period with amputation only. The latter did not receive adjuvant chemotherapy for a variety of reasons and are equated to a concurrent control group. Over the ensuing 27-66 months, 31 of 56 patients (55%) treated with regimen I and 25 of 50 (50%) treated with regimen II were disease-free. The overall disease-free survival in both regimens was 53%. This is similar to the 132 patients treated with previous adjuvant chemotherapy protocols (45-50%). However, the percentage of continuously disease-free patients treated with adjuvant chemotherapy was significantly better than the 39 patients (12%) treated contemporaneously with surgery only (P less than 0.0005). Survival in the latter is similar to that of historical control patients. These results do not suggest any change in the natural history of osteosarcoma and reveal benefits which may accrue with adjuvant chemotherapy. These results also demonstrate that in adjuvant treatment of osteosarcoma performed with ADM and MTX the high and the moderate doses of MTX are equally efficacious.
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PMID:Adriamycin-methotrexate high dose versus adriamycin-methotrexate moderate dose as adjuvant chemotherapy for osteosarcoma of the extremities: a randomized study. 349 3

The primary site of the metastasis of osteosarcoma is the lung. More than 90% of patients have died of pulmonary metastasis in one to two years. Control of osteosarcoma depend upon the prevention of its pulmonary metastasis. The introduction of chemotherapy consisting mainly of Adriamycin, high-dose methotrexate with Leucovorin rescue and Cisplatinum, dramatically improved the prognosis of osteosarcoma. In the past, when systemic chemotherapy was not available, the five-year survival rate was around 19%. In patients who receive chemotherapy with the current combination of chemotherapeutic agents (ADM, HD-MTX, VCR, CPM, CDDP), the incidence of pulmonary metastasis was low, and the five-year survival rate increased to 65%. In patients who receive chemotherapy, pulmonary metastasis may be either delayed, with a single metastasis appearing after termination of treatment (late isolated type), or early and multiple, emerging in reaction to treatment (early multiple type). It is generally accepted that post-operative chemotherapy can inhibit pulmonary micro metastasis and prove to be of great significance in improving the survival rate of patients with osteosarcoma of extremities and achieve limb salvage operation. On the other hand, effective control of the side effects of drug administration such as nausea, vomiting, alopecia, cardio (ADM) and renal (CDDP) toxicity and bone marrow suppression, is a problem that must be solved as soon as possible.
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PMID:[Significance of surgical adjuvant chemotherapy in osteosarcoma]. 349 46

Chemotherapeutical treatment with high dose methotrexate (HD-MTX) of osteogenic sarcoma has been performed at the Orthopaedic University Clinic of Vienna since 1975. In accordance with the cooperative study for osteosarcoma (Coss) which has been in use in Germany and Austria since 1977, HD-MTX has been used in larger quantity beside other cytostatic drugs. The total of 4259 g MTX has been applied to 36 patients who were suffering from malignant bone tumors. We report about the toxicity and compatibility of MTX. Within 231 cycles of treatment in 8 cases a high toxicity (grade IV after modified WHO-Score) was found. One patient died in consequence of the chemotherapy by fungal infection.
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PMID:[Compatibility and toxicity of methotrexate in the treatment of bone tumors]. 349 91

High-dose methotrexate (MTX) therapy with subsequent leucovorin (LV) rescue (HDMTX-LV) in the treatment of osteosarcoma is based on the assumption that this tumor has a deficient uptake system for MTX and reduced folates. To simulate features of HDMTX-LV therapy protocols in vitro, sensitive and MTX-resistant human osteosarcoma cell lines and a lymphoblastoid cell line were exposed to MTX and/or LV at various dosages and time schedules and the effects on DNA metabolism and on cell growth were evaluated. The data show that in osteosarcoma cells and in lymphoblasts the cytotoxic effects of 10(-6) M to 10(-7) M MTX can be substantially reversed by LV if the antidote is applied within the first 12 h of MTX exposure. The results are not consistent with the assumption mentioned above and should be taken into consideration when designing new therapeutic regimens. An alternative hypothesis for the efficacy of HDMTX-LV is discussed. It is concluded that HDMTX-LV therapy may be effective in the treatment of osteosarcoma, even when subpopulations of the tumor cells exhibit different mechanisms of resistance to MTX, such as elevated levels of dihydrofolate reductase or a deficient transport system for MTX, if high doses of MTX are applied long enough to ensure lethal intracellular MTX levels and low-dose LV schedules instituted after a long delay are used.
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PMID:High-dose methotrexate therapy with leucovorin rescue: in vitro investigations on human osteosarcoma cell lines. 349 51

The improvement of bone sarcomas prognosis during the last fifteen years (60% disease free survival at 4 years for osteogenic sarcoma, 50% for Ewing's sarcoma) is due in a large measure, to introduction of chemotherapy. ADR is a very effective agent in the treatment of those tumors but its use is limited by its cardiotoxicity. In the current chemotherapy protocols, the best results are obtained with the combination of intensive ADR-HDMTX, ADR-CDDP in osteogenic sarcoma, and ADR-ACD-CTX in Ewing's sarcoma. The ADR-Ifosfamide association seems also to be promising.
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PMID:[Role of adriamycin in the therapy of bone sarcomas]. 355 Jun 18

7-Hydroxy-MTX production after consecutive high-dose MTX therapy (12 g/m2) was measured in 7 patients with osteosarcoma by HPLC. 7-Hydroxy-MTX serum values in the last cycle were found to be significantly lower compared with the first high-dose MTX treatment of the adjuvant chemotherapy protocol (COSS 80). Moreover, in another patient highly reduced 7-hydroxy-MTX production was correlated with severe clinical toxicity. As 7-hydroxy-MTX is a 200 fold less potent dihydrofolic acid reductase inhibitor compared with MTX decreased production of the metabolite may lead to enhanced clinical toxicity which may not be predictable monitoring MTX serum levels alone.
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PMID:7-Hydroxy-methotrexate and clinical toxicity following high-dose methotrexate therapy. 385 53

High-dose methotrexate with citrovorum factor "rescue" (MTX-CF) produced an apparent complete response of the primary tumor in three patients with osteosarcoma. The response was sustained with MTX-CF, intra-arterial cis-diamminedichloroplatinum II (CDP) and Adriamycin (doxorubicin) for 18 months. Treatment was then electively discontinued. Local recurrence occurred in two patients, 6 and 4 months later, respectively. MTX-CF was reinstated and a complete response was again achieved in one patient. This has been maintained for 15+ months with MTX-CF and intra-arterial CDP administered for 13 of the 15+ months. Reinduction with MTX-CF failed in the second relapsed patient but an apparent remission was again achieved with radiation and intra-arterial CDP. This has been maintained with intravenous CDP, cyclophosphamide and phenylalanine mustard for 14+ months. A complete response in the primary tumor was still present in the nonrelapsed patient, 42 months from diagnosis. All patients have remained free of pulmonary metastases, 40+ to 42+ months from diagnosis.
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PMID:Control of primary osteosarcoma with chemotherapy. 387 85


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