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)

Twelve patients with telangiectatic osteogenic sarcoma (TOS) of the extremities were treated with neoadjuvant chemotherapy, according to two different protocols. Preoperatively the patients received high-dose methotrexate(HD-MTX)/cisplatinum(CPD) or HD-MTX/CPD/adriamycin(ADM). CPD was delivered intra-arterially, the other drugs intravenously. Limb salvage surgery was performed in eight instances and four patients underwent amputation. Post operative chemotherapy was tailored according to the grade of necrosis determined by preoperative treatment on the primary tumor. In ten cases (83%) the grade of necrosis resulted higher than 95%. The mean length of follow-up was 3.5 years with a range of 18 to 72 months. Ten patients (83%) remained continuously disease-free, while two patients developed lung metastases and died of uncontrolled disease. No local recurrences were observed. These results are better than those observed in 167 contemporary cases of conventional osteosarcoma treated with the same protocols. This study confirms that TOS is not always a lethal tumor as suggested by prior reports. Employing neoadjuvant chemotherapy a high percentage of patients with TOS can be cured and in most of them, limb sparing surgery is possible and safe.
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PMID:Primary chemotherapy and delayed surgery (neoadjuvant chemotherapy) for telangiectatic osteogenic sarcoma of the extremities. 247 10

Three therapeutic protocols were used successively for the treatment of osteogenic osteosarcoma since 1978. The first protocol associated initial surgery and 12 months of chemotherapy and was applied to 41 patients with good results in adults but poor results in children. A protocol introducing adjuvant chemotherapy based on the association of adriamycin-cisplatinum gave very disappointing results first in children and then in adults. The protocol based on HD MTX gave much more encouraging results: the long version (3 months preoperative chemotherapy) was effective in good responders but did not influence the course of poor responders. The shortened version of this protocol, derived from the T 10 Rosen protocol (1 month preoperative chemotherapy conservative surgery and appropriate peri- and postoperative chemotherapy) seems to transform the prognosis of osteosarcoma. Our current results indicate a complete primary remission rate of 89% at one year, and 83% at 33 months.
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PMID:[Comparative study of 3 successive treatment protocols of osteogenic osteosarcoma in children, adolescents and young adults. Apropos of 100 cases]. 273 37

Three adolescents and one child with osteosarcoma were studied during multiple courses of high-dose methotrexate, citrovorum factor rescue (HDMTX-CFR), with one adolescent treated intermittently over a period of 6 years. Plasma phenylalanine (Phe) and tyrosine (Tyr) were measured immediately before the infusion of MTX and then daily until serum MTX fell below 10(-7) M. At 24 hours, all showed marked increases in Phe and in the Phe/Tyr ratio. This suggests inhibition of dihydropteridine reductase (DHPR) which, in association with hepatic Phe hydroxylase, controls plasma concentrations of Phe. Inhibition of this enzyme system is not relieved by CFR. In the adolescent patients, although MTX levels in plasma declined steadily, Phe concentrations, which fell between 24 and 48 hours, rose to a new peak at 4-7 days. Possible reasons for this secondary increase are discussed. The patient with the longest exposure to HDMTX showed an increase in pretreatment Phe/Tyr ratios with time, suggesting damage to liver parenchymal cells not indicated by standard tests of liver function. Evaluation of plasma Phe during the course of HDMTX-CFR may permit assessment of intracellular concentrations of MTX or its metabolites in the liver without interference by CFR.
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PMID:Daily profiles of plasma phenylalanine and tyrosine in patients with osteogenic sarcoma during treatment with high-dose methotrexate-citrovorum rescue. 278 70

In this study we reviewed cases of osteosarcoma, malignant lymphoma of bone and Ewing's sarcoma. Historically, osteosarcoma was unresponsive to chemotherapy. Most patients were treated by radiation or amputation alone and 80% of them died from pulmonary metastasis within 2 years. Five-year survival rate was 13%. Introduction of ADM, HD-MTX and CDDP improved dramatically the prognosis of these cases. Five-year survival rate was 60%. On the other hand, 11 cases of malignant lymphoma of bone and 4 cases of Ewing's sarcoma were treated by radiation with no local recurrence. VEPA or CHOP chemotherapy was used for the former with a five-year survival rate of 45%. For the latter, T-11 protocol (Rosen) was applied, and all patients survive with no metastasis. Other organ injuries circulatory disturbance, bone necrosis and growth-disturbance of bone in radiotherapy, myocardiopathy caused by ADM and renal toxicity of CDDP are all problematic.
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PMID:[Efficacy and problems of radio- and chemo-combination therapy for malignant bone tumors]. 316 80

The bone density of two groups of patients with osteosarcoma treated with high and low doses of MTX is compared with that of a group of healthy subjects of the same age. Bone density was measured in the radius at the mid point and at the trabecular distal point. In the patients treated with low doses there were differences in bone density as compared with the controls. In those treated with high doses the bone mineral content values were significantly lower than those for the controls (p greater than 0.01) at the trabecular distal point but not at the mid point. The significant reduction in BMC in patients treated with high doses indicated that the osteopaenic effect is dose-dependent. The decrease in density only at the site at which trabecular bone is prevalent shows that MTX acts mainly at the level of this type of bone in accordance with the proven greater sensitivity of trabecular bone to the action of other osteopaenic agents.
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PMID:The effects of methotrexate (MTX) on bone. A densitometric study conducted on 59 patients with MTX administered at different doses. 322 Jul 28

From 1977 to 1982, 62 patients with various advanced malignant solid tumors were treated by HD-MTX-CFR therapy and totally 129 courses were given. Majority of the patients suffered from malignant lymphoma (10), osteogenic sarcoma (11), lung cancer (16), esophageal cancer (3), breast cancer (3) and malignant melanoma (4). All were confirmed by cytology or pathology except one primary liver cancer. There were clinically measurable lesions in 59 patients for evaluation of the treatment, and 3 osteogenic sarcoma patients without metastasis were given a postoperative adjuvant chemotherapy. 33 out of 62 had received chemotherapy and/or radiotherapy before. Dose of MTX ranged from 2 to 3 gm per course in most patients and dose of CF, from 9 to 12 mg every 6 hours for 3 days. 2 (3.4%) patients achieved complete remission (1 osteogenic sarcoma and 1 malignant lymphoma) and 8 (13.6%), partial remission (1 osteogenic sarcoma, 5 malignant lymphoma, 1 esophageal cancer and 1 breast cancer) with a total response rate of 15.9%. No response was observed in all 16 lung cancers. The main side effects of HD-MTX-CFR therapy were leukopenia, thrombocytopenia, elevation of SGPT, nausea, vomiting, mucositis, skin rash, fever and fatigue. All patients were followed more than 3 years. 4 patients are still alive (9, 9, 4 and 7 years, respectively), including 3 osteogenic sarcoma patients who received postoperative adjuvant chemotherapy and 1 mycosis fungoides.
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PMID:[High-dose methotrexate with citrovorum factor rescue (HD-MTX-CFR) in the treatment of malignant solid tumors--clinical analysis of 62 patients]. 326 85

There are still some controversy on the role of adjuvant chemotherapy in the treatment of osteogenic sarcoma, and no relevant report has been published in Chinese medical literature. In this paper 15 patients with osteogenic sarcoma treated from March 1982 to March 1986 by high dose MTX with citrovorum factor rescue after surgery are reported. Another 15 patients treated by surgical amputation alone during the same period served for comparison. The sex, age and site of the tumor in the two groups were comparable. In the treated group, MTX 0.7-1.4 g/m2, averaged 0.92 g/m2 were given intravenously, followed by citrovorum factor rescue, once a month for 2-12 injections. 12 patients (80%) in this group were given more than 4 injections. All patients tolerated the treatment well and no death was ascribed to the treatment. The patients were followed for 7-48 months, in the HD-MTX treated group, 1 patient was lost in the follow up, 9 died and 5 were still alive (35.7%). In the comparison group, 2 were lost, 11 died and only 2 were still alive (15.4%). The 2 year survival rate for the treated group was 57.1% and 30.8% for the comparison group (P greater than 0.05). The authors suggest that the dose of MTX be increased and combined with other cytostatic drugs like doxorubicin and cisplatin when necessary for better results. Adjuvant chemotherapy has definite value in the treatment of osteogenic sarcoma if adequate dose and protocols are used. However, the best adjuvant chemotherapy program for Chinese patients still remains to be studied.
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PMID:[Postoperative adjuvant chemotherapy of high dose MTX for osteogenic sarcoma]. 326 74

High-dose methotrexate (HDMTX) with leucovorin (LV) rescue has been used as a therapeutic strategy in oncology for more than a decade. Administration of HDMTX results in tumoricidal plasma concentrations of the drug without significant host toxicity, provided that plasma MTX levels are monitored and LV rescue is properly administered. The original premise of LV rescue was that the provision of reduced folate to normal cells would circumvent the metabolic block produced by MTX and allow resumption of DNA synthesis, although the presumed therapeutic selectivity of leucovorin has not yet been adequately explained. Despite a strong pharmacologic rationale and a vast clinical experience, HDMTX with leucovorin rescue has not been shown to be unequivocally superior to conventional doses of MTX in any clinical situation except, perhaps, for treatment of osteogenic sarcoma and childhood acute leukemia. While HDMTX is an important component of effective treatment regimens for these diseases, its precise contribution to the success of these regimens remains undefined. Although HDMTX can theoretically overcome all known mechanisms of MTX resistance, no data exist to suggest that this can be accomplished in the clinic. Thus, this well-known but poorly understood treatment regimen must remain a subject of clinical investigation rather than a part of routine clinical practice.
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PMID:High-dose methotrexate: a critical reappraisal. 331 19

Thirty-two patients with osteosarcoma of the femur and the tibia were treated with systemic chemotherapy and radical surgery between 1976 and 1984. Adriamycin (ADR) alone, ADR plus high-dose methotrexate with citrovorum factor (HD-MTX-CF) (protocol A) and ADR plus HD-MTX-CF plus cis-platinum plus bleomycin, cyclophosphamide and actinomycin-D (BCD) (protocol B) were given as chemotherapeutic regimens. Twenty-nine out of 32 patients received chemotherapy both preoperatively and postoperatively, and eleven of 29 patients had a good response. Amputation was performed on 19 patients and en bloc resection on 13 patients. No local recurrence was detected in any of the 32 patients. The disease-free survival rate was 35%. Disease-free survival rate of patients treated with protocol A and protocol B was 25% and 91% respectively. Fourteen out of 17 patients who developed pulmonary metastasis underwent thoracotomy. Survival rate after thoracotomy was 50%. The overall survival rate of 32 patients with osteosarcoma was 56%.
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PMID:Treatment for osteosarcoma--a study of thirty-two patients treated with systemic chemotherapy and radical surgery. 345 79

The primary site of metastasis of osteosarcoma is the lung. In the past, even if the primary lesion was completely removed by radical surgery, more than 90% of patients of died pulmonary metastasis with in one to two years. Control of osteosarcoma therefore depends upon the prevention and treatment of its pulmonary metastasis. The introduction of chemotherapy consisting mainly of Adriamycin and high-dose methotrexate with Leucovorin rescue, dramatically improved the prognosis of osteosarcoma. In the past where systemic chemotherapy was not available, the five-year survival rate was around 19%. The majority of patients developed bilateral pulmonary metastasis within one year after onset, and died. These patients exhibited numerous micro-metastases as well. In patients receiving surgical adjuvant chemotherapy with 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, a single metastasis appearing after the termination of treatment, or early and multiple, appearing resistant to treatment. Surgery is indicated in the former situation while some therapeutic system must be devised for the latter. Recently, preoperative chemotherapy for limb-saving is given to patients with osteosarcoma of the extremities (NSH-3, 4, 5). The adjuvant of chemotherapy proved to be of great significance for improving the survival rate of osteosarcoma and for achieving limb salvage.
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PMID:[Surgery and adjuvant chemotherapy of osteosarcoma]. 346 May 27


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