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)

Adriamycin is a new anticancer antibiotic with a wide spectrum of activity against solid tumours. The results obtained with this agent in 159 patients with histologically confirmed advanced metastastic malignancies are reported. Encouraging results were obtained in patients with sarcomas of bone and soft tissue (12/22). Response was also seen in mesothelioma (3/9) and lung cancer (5/15). A variety of other neoplasms was also treated and results obtained in neuroblastoma, testicular tumours, stomach carcinoma, breast cancer and nephroblastoma are reported. Treatment is discussed, with reference to response rates and toxicity. Results in 72 patients with advanced breast cancer, who received adriamycin in combination with other chemotherapeutic agents, are presented. Seventeen patients with primary liver cancer were also treated with adriamycin. To date, this is the only chemotherapeutic agent that appears to significantly improve survival times in patients with this resistant form of cancer. The prophylactic use of adriamycin against osteogenic sarcoma is also discussed.
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PMID:Adriamycin in the treatment of cancer. 125 Dec 78

The reliability of a simple method evaluating the pattern of subcellular binding of Adriamycin (Adriamycin binding assay, ABA) as an index of sensitivity was demonstrated in different primary cultures and in sensitive and resistant cell lines of human osteosarcoma. After exposure to Adriamycin (10 micrograms/ml for 30 min at 37 degrees C), living sensitive cells showed selective intranuclear uptake of the drug, whereas in resistant cells no distinct subcellular distribution was observed. The binding pattern of Adriamycin in sensitive and in highly resistant cells was inversely related to the expression of P-glycoprotein. However, low levels of resistance in vitro, not detectable by increased levels of expression of P-glycoprotein, were revealed by ABA. The use of ABA in combination with the estimate of P-glycoprotein expression is recommended in clinical practice as an accurate means for predicting the sensitivity of osteosarcoma to Adriamycin.
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PMID:Adriamycin binding assay: a valuable chemosensitivity test in human osteosarcoma. 135 94

Osteosarcoma includes several distinct varieties. It is therefore essential to rely upon a very specialized pathologist. It is necessary to stage the tumor and to histologically define the oncologic quality of the surgical removal (surgical margins). The limb salvage surgery in osteosarcoma involves several areas of risk: the biopsy, the extension of the tumor in the marrow spaces and canal, the impingement or plugging of the vessels by the tumor, the invasion of the joint tissues, the contamination of the joint space and/or soft tissue compartments. The reconstruction after bone segmental resection involves many problems, including long-lasting prostheses, bone bank, microsurgical techniques--the preoperative chemotherapy dramatically reduced the need for amputation, in favour of conservative surgery. A good response to chemotherapy (almost total necrosis of the tumor), is the most important factor correlated with a favorable prognosis. The more recent protocols aim to increase the tumor response and the survival rate through a very intense primary chemotherapy, using Adriamycin, high-dose Methotrexate, Cisplatin and Ifosfamide.
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PMID:[Osteosarcoma]. 141 68

The chemotherapeutic approach to advanced sarcomas of bone and soft tissue is reviewed. The most active single agents against osteosarcoma are doxorubicin (overall response rate, 21%), methotrexate (30% to 40%), cisplatin (25%), and ifosfamide (28%). Current multimodality treatment for Ewing's sarcoma consists of combination chemotherapy with doxorubicin, vincristine, and cyclophosphamide (or ifosfamide in current trials) prior to and concurrent with radiation therapy for the involved bone. In soft tissue sarcomas, doxorubicin is the most active single agent, with overall response rates ranging from 15% to 35%. Dacarbazine has a single-agent response rate of 16%. Ifosfamide has documented activity in sarcoma patients who have failed treatment with doxorubicin-containing regimens. The combination regimen currently producing the highest response rates in soft-tissue sarcomas is doxorubicin/dacarbazine/ifosfamide. Doxorubicin and dacarbazine should be administered by continuous infusion to reduce the severity of nausea and vomiting and the risk of cardiotoxicity. Ifosfamide can be given by continuous infusion or in divided doses with mesna to mitigate urothelial toxicity.
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PMID:Chemotherapy of advanced sarcomas of bone and soft tissue. 148 69

Rothmund Thomson syndrome (RTS) is a rare autosomal recessive disorder characterised by poikiloderma, dermal atrophy, dystrophic nails, short stature and hypogonadism. An increased incidence of malignancy has been reported in patients with this syndrome secondary, it is postulated, to DNA repair defects. We report the occurrence of an osteogenic sarcoma in an 11-year-old Irish girl with RTS. Although fibroblast cultures demonstrated enhanced radiosensitivity, there was no undue toxicity associated with treatment, which included methotrexate, cisplatinum and Adriamycin. Following conservative surgery, she is currently off treatment and disease-free 2 years from diagnosis.
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PMID:Osteogenic sarcoma and Rothmund Thomson syndrome. 158 68

Adjuvant therapy is currently established in the treatment of osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma. Of the 12 reported randomized studies of adjuvant chemotherapy for soft tissue sarcoma, only 2 show a significant overall survival advantage for chemotherapy (the most important endpoint). In three randomized trials, the survival of the observation arm exceeds that of the chemotherapy arm. In two additional studies, subset analyses currently indicate a significant DFS advantage for adjuvant chemotherapy in extremity lesions, but no significant improvement in survival. Although initial NCI reports showed significantly prolonged survival for the subset of chemotherapy-treated extremity primaries, survival on longer follow-up is no longer significantly different. In the subset analysis of retroperitoneal sarcomas in the same NCI study, the survival of the control group is superior to the treatment group. Doxorubicin associated cardiotoxicity has occurred in about 10% of treated patients, occasionally contributing to treatment-related deaths. Based on these data, adjuvant chemotherapy should be considered investigational for adult soft-tissue sarcomas of any primary site. Future randomized trials should include patients at high risk for metastases (large, high-grade lesions) with a reasonable likelihood of local control by radical resection, or resection with uninvolved margins and subsequent radiotherapy. Low-grade sarcomas are currently cured by surgical resection in 80% of cases, and thus should not be included in adjuvant trials.
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PMID:Adjuvant therapy for sarcomas. 177 77

The Pediatric Oncology Group compared two regimens that employed involved field radiotherapy 3,500 rad and either MOPP + Bleo or A-COPP chemotherapy, given in a sandwich fashion, as treatments for stage III Hodgkin's disease in children under the age of 18 years. Eighty-four surgically staged children from the United States and Mexico who had been randomly assigned to treatment during the period from July 1976 through October 1982 were evaluated. Unfavorable disease characteristics were distributed equally between the treatment groups. The percentages of children achieving complete remission by regimen were 84% for MOPP + Bleo and 92% for A-COPP. For those continuing in complete remission, the percentages were 71% for MOPP + Bleo and 72% for A-COPP. For those surviving 9 years, the percentage was 84% for MOPP + Bleo and 85% for A-COPP. The presence of low abdominal disease at diagnosis did not adversely influence response to therapy or survival. All deaths among MOPP + Bleo cases occurred within 4 years of study entry; 3 late deaths in A-COPP cases at 8-10 years were due to osteosarcoma, cardiopathy, and recurrent Hodgkin's disease. The preferred treatment regimen for future use cannot be determined until the cardiotoxicity of Adriamycin is eliminated by the development of drug delivery techniques that reduce cardiotoxicity or anthracycline congeners that are not cardiotoxic.
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PMID:Comparative effectiveness of two combined modality regimens in the treatment of surgical stage III Hodgkin's disease in children. An 8-year follow-up study by the Pediatric Oncology Group. 178 72

A rapid, simple chemosensitivity assay, assessing tumor cell nuclear uptake of doxorubicin hydrochloride, was evaluated in 16 dogs with appendicular osteosarcoma. Doxorubicin was administered to dogs in 5 biweekly treatments, and surgical resection was performed after the second or third treatment. The chemosensitivity assay was performed on biopsy specimens from all dogs before chemotherapy. It was repeated on tissue from resected tumors, and tumors were evaluated histologically to determine the degree of necrosis resulting from chemotherapy. Disease-free and total survival time correlated significantly (P less than 0.05 in both cases) with the degree of postchemotherapy necrosis of the primary tumors. Significant correlation was not apparent between the percentage of tumor cells with nuclear uptake of doxorubicin (in either biopsy or resection samples) and disease-free or total survival time. The percentage of cells with nuclear uptake of doxorubicin in surgically resected tumors correlated significantly (P less than 0.05) with percentage of necrosis.
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PMID:In vitro assay of nuclear uptake of doxorubicin hydrochloride in osteosarcoma cells of dogs. 178 8

From January 1983 to August 1987, 29 evaluable patients with high-grade osteosarcoma were treated in our institution with preoperative intra-atrial cisplatin, 100 mg/m2 every 14 days for three courses. Surgery was done on day 42. Surgery consisted of limb salvage in six, amputations in 15, and disarticulations in eight. Postoperative chemotherapy included Adriamycin (ADR), 45 mg/m2 for 2 days every 6 weeks, alternated with cisplatin 120 mg/m2 every 6 weeks. The nephrotoxicity (18 out 29) was reversible in all cases. Cardiotoxicity was prominent; it was observed in 31% of patients. In six, there was congestive heart failure, but there were no fatal cases. The hematological toxicity was severe. There were three patients with fatal infections who had no evidence of disease after they had finished treatment. Seventeen of 29 patients (58.6%) were good responders and showed 60-100% tumoral necrosis after intra-atrial cisplatin. The 6-year, relapse-free survival rate was 58.6%--70.5% for the good responders and 41.6% for the poor responders (p less than 0.05). The size of the tumor was the other important prognostic factor. The rate of 6-year, relapse-free survival was 73.6% for small tumors (those measuring less than 100 cm2) and 33.3% for large tumors (p less than 0.05).
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PMID:Intra-arterial cisplatin given prior to surgery in osteosarcoma: grade of necrosis and size of tumor as major prognostic factors. 179 51

Preoperative intraarterial (IA) cisplatin (CDP) was administered to 92 patients with nonmetastatic osteosarcoma. The ages of the patients ranged from 4 to 28 years. Sixty-four patients (70%) received 2 or 3 preoperative courses and 28 (30%) received 4 or more. Sixty-two specimens were available for pathologic examination to assess the degree of tumor necrosis. More than 90% tumor destruction was observed in 16 of 42 patients (38%) who received 1 to 3 preoperative courses as opposed to 17 of 20 (85%) who received 4 or more courses. Patients who received 4 or more courses had a 2-fold probability of achieving more than 90% tumor necrosis, and 68% underwent conservative surgery. Of those who received 3 or less courses, 23% underwent conservative surgery. Postoperatively, patients were treated with intravenous (IV) CDP alternating with doxorubicin (ADR) (Adriamycin, Adria Laboratories, Columbus, OH). Pulmonary metastases developed in 36 patients, bone metastases in 2, and local recurrence in 6. Two patients died of cardiac failure without evidence of disease. Thus, 46 patients (50%) were continuously free of disease 18 to 78 months after diagnosis. Univariate and multivariate analyses showed that male sex, low grade preoperative chemotherapy-induced necrosis, and nonosteoblastic histologic condition were prognostic factors predictive of recurrence, while male sex and large tumor size were prognostic factors predictive of death. These results are comparable with those reported by other centers and are superior to our previous experiences that yielded survival rates of 5% to 10%. A substantial number of patients also had the opportunity to achieve tumor removal with conservative surgery.
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PMID:Increased survival, limb preservation, and prognostic factors for osteosarcoma. 185 72


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