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)

High-dose methotrexate with leucovorin rescue was used alone or in combination with Adriamycin and cyclophosphamide for the treatment of 27 osteosarcoma patients with measurable indicators of disease. Three patients developed complete responses of measurable lesions, two had partial responses, two had static disease, one had symptomatic improvement, and one had return to normal of physical findings following treatment of a flat bone primary osteosarcoma. While the doses and frequency of administration of high-dose methotrexate differed from those used by previous investigators, these results suggest that aggressive treatment with high-dose methotrexate must be attempted to further evaluate its efficacy as single-agent therapy for osteosarcoma patients not eligible for adjuvant chemotherapy trials.
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PMID:High-dose methotrexate used alone and in combination for measurable primary or metastatic osteosarcoma. 696 35

Eighteen patients with osteosarcoma, most of whom were adolescents, were examined for abnormalities of the brain by use of computed axial tomography. These studies were performed at 15-60 months (median 47 months) after the completion of adjuvant chemotherapy, which included high-dose methotrexate, cyclophosphamide, and Adriamycin. No abnormalities were found. The results of this study, together with the absence of brain lesions in published reports in children receiving high-dose methotrexate but no cranial irradiation, indicate that delayed neurotoxicity is not a major complication of this form of therapy in older children.
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PMID:Normal computed tomograms of the brain in osteosarcoma patients treated with high-dose methotrexate. 697 2

From 1975 through 1979, 25 patients with osteosarcoma received therapy with vincristine, high-dose methotrexate, citrovorum factor, and Adriamycin. Five patients had metastases prior to receiving chemotherapy, and 11 of the remaining 20 nonmetastatic patients received preoperative or preirradiation chemotherapy. Chemotherapy caused objective tumor regression in 1 of 5 patients with metastases and 1 of 11 with measurable primaries. All five patients with metastatic disease died 7-16 months from diagnosis. Of the 20 nonmetastatic patients, 4 did not have primary amputations: all died. Of 16 patients with primary amputations, 6 are alive relapse-free 24-86 months from diagnosis, and 10 are dead. The actuarial survival of 36% is not statistically different from that of historical control groups or from that of concurrent control groups treated with surgery alone. However, because most adjuvant chemotherapy studies have involved few patients, 36% survival is not statistically different from the 50-70+% survival reported in previous studies. Our data fail to demonstrate that the adjuvant chemotherapy has improved the survival rate of children with osteosarcoma. We support a randomized, controlled comparison of adjuvant chemotherapy and aggressive surgical resection.
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PMID:High-dose methotrexate and adriamycin in osteogenic sarcoma: the children's hospital of Philadelphia study. 697 38

A review of the steps by which the current adjuvant chemotherapy programs for osteosarcoma (COMPADRI-V) evolved over the past 19 years indicates that among the important concepts incorporated into the program are demonstration of antitumor activity of each component, adequate evaluation of patient tolerance of the treatment regimen, progressive improvement in documented treatment results, and concomitant utilization of pharmacokinetic information. The current program utilizes intensified high-dose methotrexate and Adriamycin courses and preoperative chemotherapy. The regimen has permitted ready amalgamation of limb-salvage programs. The success of these approaches is emphasized by the overall survival rate of 79% at three years for the patients with osteosarcoma treated at M. D. Anderson Hospital.
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PMID:Multidrug chemotherapy in osteosarcoma. 700 13

The Surgery Branch of the National Cancer Institute conducted two prospective trials on the effectiveness of adjuvant chemotherapy in the treatment of patients with sarcomas. Adriamycin and cyclophosphamide (Cytoxan) appeared to improve significantly the disease-free survival of 55 current protocol patients with sarcomas of soft tissue compared with historical controls (P less than 0.001). The high incidence of drug-induced cardiomyopathy associated with this regimen led us to begin a prospective randomized trial of this adjuvant chemotherapy in patients with sarcomas of soft tissue. The use of high-dose methotrexate following surgery in 50 patients with osteogenic sarcoma was associated with a small increase in disease-free survival (P = 0.028) compared with historical controls. Little if any effect was seen in patients with high-grade lesions (P = 0.11). Overall survival of patients with osteogenic sarcoma was dramatically improved (P less than 0.001), probably due to the introduction of frequent screening for pulmonary metastases and the surgical resection of these metastases as soon as they appeared.
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PMID:Treatment of soft tissue and bone sarcomas: review of studies at the National Cancer Institute. 702 92

A dose-intensive regimen of cyclophosphamide (140 mg/kg over 2 days), doxorubicin (Adriamycin, 75 mg/m2 over 3 days), and vincristine (1 mg/m2 on days 1, 2, and 3 and 1.5 mg/m2 on day 9) was tested in 18 children and adolescents with poor-prognosis recurrent or refractory solid tumors. Nine were affected by neuroblastoma, 3 by Ewing's tumors, 2 by rhabdomyosarcoma, 2 by synovial sarcoma, 1 by hepatocellular carcinoma, and 1 by osteogenic sarcoma. All enrolled patients were heavily pretreated, including 2 patients after bone marrow transplantation. Forty courses were applied (median, 2). The overall response rate was 33% (2 complete remissions and 4 partial remissions). Responses were obtained in children with neuroblastoma, Ewing's tumors, and hepatocellular carcinoma. Myelosuppression [World Health Organization (WHO) grade IV after all courses] and cardiac toxicity (3 WHO grade I, 5 WHO grade III, and 3 WHO grade IV) were the main side effects. Nephrotoxicity and hepatoxicity were not observed. With further therapy consisting of surgery, radiotherapy, and high-dose chemotherapy [cisplatin, carboplatin/etoposide (VP16), or ifosfamide/VP16 with or without autologous stem cell reinfusion after conditioning with melphalan/VP16/carboplatin], 3 complete remissions and 5 very good partial remissions were obtained. Ten of 18 patients are alive after a median follow-up of 16 months.
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PMID:High-dose cyclophosphamide, adriamycin, and vincristine (HD-CAV) in children with recurrent solid tumor. 785 84

Adjuvant chemotherapy is currently employed in the treatment of patients with osteosarcoma, but the drug regimens, although effective in improving disease-free survival, are unsuccessful in 20-40% of patients and very toxic. It would be useful to know whether tumor cells are sensitive to a given drug prior to its use. To this end, we developed a method of assessing Adriamycin (doxorubicin) binding to tumor nuclei as a possible means of detecting sensitivity to the drug. Adriamycin-sensitive murine osteosarcoma cells were used to develop the assay. The in vitro conditions (drug concentration, duration of incubation, and temperature) were optimized with use of the murine osteosarcoma cells in culture. After the cells had been incubated with Adriamycin, cell viability was determined and Adriamycin fluorescence intensity was measured with a cytofluorometer. The optimal parameters for Adriamycin binding were found to be a 30-minute incubation in a 10 micrograms/ml concentration of Adriamycin at 37 degrees C; the frequency of cells that emitted Adriamycin fluorescence from the nucleus compared with the total number of living cells reached 100% under these conditions. In a murine leukemia cell line with known sensitivity to Adriamycin, the cells emitted red fluorescence from the nucleus and cytoplasm, whereas in a resistant line the cells emitted Adriamycin fluorescence from only the cytoplasm. We demonstrated that it is possible to differentiate nuclear from cytoplasmic concentration of Adriamycin in a tumor cell with use of a fluorescent microscope and that resistant cell lines can be distinguished from sensitive cell lines by this method.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An assay to measure adriamycin binding in osteosarcoma cells. 793 78

Intratibial injection in nude rats of 1 x 10(6) OHS, MHMX, and LOX human tumor cells resulted in each case in progressively growing bone tumors. When the diameter of the affected leg had increased by 2-3 mm, the animals were examined for uptake of 99mTc-methylenediphosphonate. The OHS osteosarcoma tumors caused sclerotic lesions with high and uniform isotope uptake, and the MHMX unclassified sarcoma showed a mixed pattern with both sclerotic and lytic areas, whereas the LOX melanoma caused lytic bone lesions with low uptake of the radionuclide. These findings were compared with the results of analogous investigations previously performed in the patients from whom the tumor lines originated. Striking similarities in both the morphology and the scintigraphic images were observed between corresponding tumors in rats and humans, with results supporting the clinical relevance of the model systems. When the LOX model was used for therapy experiments, doxorubicin had no effect on the growth of the tibial tumors, which in the control group appeared after a latency of 13.5 days. The alkylating agent mitozolomide increased the median tumor-free latency to 47 days in 7 rats, and 5 animals did not develop tumors within the observation period of 60 days. Doxorubicin was ineffective also against the OHS tumor, whereas ifosfamide and the radionuclide 89Sr-chloride showed significant antitumor activity. The disease-free latency increased from 20 days, in the control animals, to 45 and 28.5 days, respectively, in the 2 treated groups, in which 2 of 7 and 2 of 10 rats were without tumors at 60 days. The data demonstrate that the tibial models discriminated between the action of the different therapeutic agents, and suggest that they may be useful in selecting compounds with clinical activity against skeletal tumors.
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PMID:Validity and usefulness of human tumor models established by intratibial cell inoculation in nude rats. 813 86

Liposomal muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) is a biological agent in phase I and II trials for osteosarcoma and melanoma. Its mechanism of action has been linked to its ability to activate monocyte tumoricidal function and to stimulate monocyte production of tumor necrosis factor (TNF) and interleukins(IL)-1, -6, and -8. Our ultimate goal is to combine L-MTP-PE with chemotherapy. The purpose of this study was to determine whether doxorubicin (Adriamycin) interfered with the ability of L-MTP-PE to activate monocyte cytokine production. Human monocytes were cultured with or without 5-500 ng/ml of Adriamycin for 3 h and washed before being exposed to 2 micrograms/ml L-MTP-PE for 16 h. Cultured supernatants were collected and assayed for TNF, IL-1, IL-6, and IL-8. The messenger RNA expression of IL-1 alpha, IL-1 beta, TNF alpha, IL-6, and IL-8 was quantified with northern blot analysis. Adriamycin did not suppress the up-regulation of any of these cytokines. We concluded that combination therapy with L-MTP-PE and Adriamycin is feasible and that this combination warrants further investigation in a clinical setting.
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PMID:Effect of Adriamycin on liposomal muramyl tripeptide's ability to up-regulate monocyte cytokine expression. 824 65

Twenty-nine patients with high-grade nonmetastatic osteogenic sarcoma of the extremities were treated with adjuvant chemotherapy following definitive surgery. Chemotherapy consisted of systemic intravenous Adriamycin and cisplatin in a sequential fashion given for six courses. Nineteen out of 29 patients are alive and continuously disease free over a follow-up period ranging from 9+ to 30+ months. The relapse-free survival was 72%, and overall survival for the entire group was 69%. Median survival is not reached yet. Six out of 29 patients relapsed, of which 1 patient is alive for 6+ months after relapse. Three patients died of chemotherapy toxicity. The results were superior to historical controls treated with surgery alone. The need for more aggressive treatment approaches is discussed.
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PMID:Adjuvant chemotherapy for osteogenic sarcoma of the extremity with sequential adriamycin and cisplatin. 844 Dec 77


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