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 the inception of adjuvant chemotherapy for osteogenic sarcoma (OS), 25 patients were treated for telangiectatic osteogenic sarcoma (TOS) from 1973 through 1980. This represented 12% of all patients with primary OS of an extremity seen during this time period. Tumors that demonstrated only focal areas of TOS with areas of other subtypes were designated not as TOS but as "mixed" subtypes of OS. In the 25 patients with pure TOS, surgery included 18 amputations and seven resections for the primary tumor. Ten patients were treated on the first chemotherapy protocol (T-4) including high-dose methotrexate (HDMTX) with citrovorum factor rescue (CFR), Adriamycin (ADR), and cyclophosphamide (CYC). Of those 10 patients, five have been free of disease for seven to ten years from the time of diagnosis. Nine patients were treated on the second protocol (T-7) including HDMTX with CFR, ADR, and the combination bleomycin, cyclophosphamide, and dactinomycin (BCD). Six of those nine patients are disease-free survivors 63 to 88 months (median, 63 months) from diagnosis. Six were treated on the third chemotherapy protocol (T-10) including HDMTX with CFR, ADR, BCD, and the substitution of cisplatinum for those not having a complete response to preoperative chemotherapy with HDMTX. All six of the latter are disease-free survivors 42 to 56 months (median, 49 months) from the start of treatment. Toxicity included two HDMTX-related drug deaths in patients started on treatment prior to 1977. Of the entire group, 17/25 (68%) have remained free of disease at a mean follow-up time of over five and one-half years. This study demonstrates that TOS is responsive to chemotherapy and is potentially curable. Some prior reports of the uniformly poor prognosis of this variant of OS should not discourage attempts of curative therapy by chemotherapy and surgery.
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PMID:Telangiectatic osteogenic sarcoma. Improved survival with combination chemotherapy. 242 60

Although chemotherapeutic drugs are frequently administered to patients with osteosarcoma, there has been little research into the effect of cytotoxic drugs on osteosarcoma cell biology. The effect of two drugs (Adriamycin and bleomycin) on cell cycle kinetics was investigated in vitro in an established line of human osteosarcoma cells and in vivo using the Dunn osteosarcoma model. The cell cycle changes were consistent with G2 arrest for both drugs in vivo and in vitro. The alteration in cell cycle distribution was correlated with inhibition of 3H-thymidine incorporation in vitro. In vivo, the greater change in cell cycle distribution caused by Adriamycin was reflected in the increased inhibition of tumor growth found with this drug.
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PMID:Kinetic effects of adriamycin and bleomycin on two osteosarcoma models. 244 44

From this review of chemotherapy trials, several observations can be made. Osteosarcoma is a complex disease involving multiple histologies, each with a different prognosis. Prognostic factors that have been shown to be important include anatomic location of the primary tumor, stage at presentation (patients with metastatic or local recurrent disease fair far worse than those with primary disease), age at onset (children fair worse than the teenager with osteosarcoma), and location within the extremity (patients with more distal tumors fairing better than patients with more proximal tumors). There is convincing evidence for the efficacy of chemotherapeutic agents such as methotrexate in high doses (at least 8 g/m2 for adults, 12 g/m2 for children), Adriamycin, and cisplatin. The combination of Adriamycin and cisplatin appears to be more beneficial relative to either one of these agents alone. The efficacy of the combination of BCD as a triple-drug regimen, although useful in several different trials, has not been convincingly shown. Finally, from several of the recent randomized trials, it appears, that chemotherapeutic regimens containing an Adriamycin and cisplatin combination appear to be superior to those that do not include this combination. However, these observations are made from a historical perspective and have not been conclusively proven by randomized prospective investigations. The observations concerning the natural history of the disease and the activity of various chemotherapeutic agents suggest certain clinical practice algorithms. Essential staging procedures would include a bone scan looking for multifocal or metastatic disease, and CT scans of the chest looking for metastases to the lung. From all studies, it is apparent that surgery is mandatory for the primary tumor and should be an integral portion of all treatment methods. Chemotherapy should be considered for all patients with osteosarcoma, and the essential drugs in the regimen appear at present to minimally include high-dose methotrexate, Adriamycin, and cisplatin. It would also appear from several of these reports that not only is the adjuvant use of these chemotherapeutic agents indicated, but that the preoperative use of these agents has had significant advantages. The neoadjuvant chemotherapy begins the essential systemic chemotherapy at a very early stage, allows histologic assessment of treatment effect, permits altering drug regimens postoperative, and in many reported trials has allowed less than amputative surgery (limb salvage) to be performed. Finally, close follow-up of patients with osteosarcoma has therapeutic value.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Adjuvant chemotherapy for osteosarcoma. 266 46

Because treatment with surgery and combination chemotherapy produces a high cure rate in young men with osteosarcoma, their subsequent reproductive function is an important concern. Semen analyses of osteosarcoma patients, therefore, were performed before, during, and after treatment with the PADIC regimen consisting of cisplatin, Adriamycin (doxorubicin), and dacarbazine or, in some cases, the PADIC regimen plus additional drugs. Results showed that semen volume was not affected and that sperm motility was reduced only during treatment. Although nearly all patients were rendered azoospermic during treatment, sperm production resumed in 30 of 32 patients examined at least 2 years after treatment. Analysis with correction for censored data indicates that, in 78% of treated men, sperm counts will return to more than 10 million/ml. The percentage of men whose sperm counts recovered to normal was lower for those receiving cisplatin dosages greater than or equal to 600 mg/m2; no trends were observed with Adriamycin and dacarbazine dosages. The inclusion of additional drugs such as methotrexate, bleomycin, dactinomycin, or cyclophosphamide (less than 4 g/m2) did not significantly affect the recovery of spermatogenesis. We conclude that the risk of long-term infertility from treatment with the PADIC regimen is low.
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PMID:Recovery of sperm production after chemotherapy for osteosarcoma. 272 May 62

The effects of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3), 1 alpha-hydroxyvitamin D3 (1 alpha(OH)D3), and dexamethasone on colony formation of Dunn osteosarcoma cells (TA 102 cells) were investigated. Concentrations of 1 alpha,25(OH)2D3, 1 alpha(OH)D3, and dexamethasone at which they exerted 50% reduction of the total area of TA 102 colony formation were 9 X 10(-9) M, 9 X 10(-8) M, and 5 X 10(-6) M, respectively. Effects of anticancer drugs on TA 102 cells were also investigated and concentrations needed for 50% growth inhibition (50% inhibitory concentration values) of cis-platinum, mitomycin C (MMC), methotrexate (MTX), and Adriamycin (ADR) against TA 102 cells were calculated to be 0.07 microgram/ml, 0.0008 microgram/ml, 0.0008 microgram/ml, and 0.0005 microgram/ml, respectively. The simultaneous treatment of TA 102 cells with 10(-8) M of 1 alpha,25(OH)2D3 and anticancer drugs significantly enhanced the respective inhibitory effects on colony formation. In this treatment, the IC50 value of MMC was calculated to be 6.4 X 10(-6) micrograms/ml, which was 1/160 of the expected IC50 value of MMC (8 X 10(-4) micrograms/ml). Similar synergistic effects were observed when the cells were treated with 1 alpha,25(OH)2D3 and low concentrations of cis-platinum, MTX, or ADR.
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PMID:1 alpha,25(OH)2D3 exerts cytostatic effects on murine osteosarcoma cells and enhances the cytocidal effects of anticancer drugs. 279 95

Preoperative chemotherapy for primary osteosarcoma has usually been accompanied by a prolonged delay between withdrawal before operation and resumption after. This is because animal studies showed impaired wound healing associated with perioperative chemotherapy. Clinical studies, however, have not shown this to be the case. The authors describe their experience in eight patients who had osteosarcoma and Ewing's sarcoma of the extremities and received one to three cycles of chemotherapy preoperatively. Chemotherapy consisted of Adriamycin, cis-platinum and vincristine. Definitive surgery on the primary tumour was done 1 to 4 days after the last dose. Amputation was performed on seven patients and tumour resection for limb salvage on one. No wound healing or infectious complications were encountered. The ensuing course of chemotherapy was not delayed by the surgical procedure. The authors conclude that it is feasible to combine neoadjuvant chemotherapy and early surgery in the management of high-grade primary bone sarcoma.
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PMID:Perioperative chemotherapy for primary sarcoma of bone. 291 Mar 79

The chest wall is an infrequent site of malignancy in infancy and childhood. Management of these tumors, however, is of particular concern because of their aggressive behavior and the functional impairment which may result from local treatment. From 1976 to 1987 we have treated seventeen infants and children with tumors of the chest wall. Askin's tumors and Ewing's sarcoma were considered as a single entity, malignant small round cell tumor (MSRCT), and account for the majority (11 of the 17 patients). Other tumors represented were infantile fibrosarcoma (1), undifferentiated spindle cell sarcomas (2), osteogenic sarcoma (1), large cell lymphoma (1), and synovial sarcoma (1). Nine of 17 patients have survived (median follow-up of survivors 5 years); six patients died of disease and two from complications of therapy. All four patients with MSRCT and metastasis at diagnosis died of disease despite chemotherapy and radiotherapy. Four of the seven patients with localized MSRCT, who received combined modality therapy including resection (two after initial chemotherapy), radiotherapy, and chemotherapy, were continuously disease-free 16 months to 10 years following diagnosis. One of the three patients who failed died of complications of surgery to her extensive primary. A second patient had a relapse of disease in a hilar node four years after finishing vincristine, actinomycin, and cytoxan (VAC) chemotherapy; she was retreated with Adriamycin (doxorubicin, Adria Laboratories, Columbus, Ohio), vincristine, and cyclophosphamide as well as radiotherapy to her hilum and remains in second remission 56 months following her recurrence. The third patient suffered a distant relapse in bone and, before succumbing to his MSRCT, developed acute monocytic leukemia and died during a remission induction attempt. Mixed results were obtained for the patients with other tumor types.
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PMID:Chest wall tumors in infancy and childhood. 291 83

Fifty-three patients who had a high-grade osteosarcoma had either a limb-salvage resection or an amputation. They all received adjuvant therapy that consisted of administration of Adriamycin (doxorubicin) and whole-lung irradiation. At the time of follow-up, the surgical margin was assessed by examination of the surgical specimen. Each patient was followed for at least three years or until death. The data suggested that a wide surgical margin is adequate to control a primary osteosarcoma. When a wide surgical margin can be used and a functional limb can be salvaged, an amputation probably is not required.
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PMID:Surgical treatment for osteosarcoma. 316 61

The purpose of these studies was to determine the effect of Adriamycin (ADR) on the ability of liposome-encapsulated immunomodulators to activate human blood monocytes to the tumoricidal state. We undertook these experiments because we envisioned using encapsulated activators in addition to chemotherapy to destroy pulmonary micrometastases in patients with osteosarcoma (OS). Prior to the initiation of such therapy, it was important to determine whether chemotherapy interferes with monocyte function. First, human peripheral blood monocytes were isolated from normal donors and preincubated with ADR (0.5-500 ng/ml) for 1 h and then washed prior to the addition of free or liposome-encapsulated activators. After 18-24 h incubation, the activating agents were washed off and [125I]IdUrd-labeled A375 melanoma cells were added. Lysis of radiolabeled tumor cells was quantified 72 h later. Monocytes were also incubated with ADR for 24 h in the presence of free or liposome-encapsulated activators and their cytotoxicity quantified. ADR had no effect on the ability of either free or liposome-encapsulated agents to activate monocyte tumoricidal function. We also studied the in vivo effect of ADR therapy on monocyte function in nine patients with OS. At the time of diagnosis and 1 month after ADR therapy (75 mg/m2) patient monocytes could be activated to the tumoricidal state by liposome-encapsulated agents at levels equal to or greater than pretherapy levels. Monocytes isolated from four patients with OS 1 day after ADR therapy and then activated by liposome-encapsulated agents also demonstrated tumoricidal activity. These studies indicated that the monocytes isolated from osteosarcoma patients treated with ADR can be activated in vitro to kill tumor cells and that additional therapy with liposome-encapsulated immunomodulators may be combined with ADR in the treatment of metastatic pulmonary OS.
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PMID:In vitro and in vivo effect of adriamycin therapy on monocyte activation by liposome-encapsulated immunomodulators. 326 32

Methotrexate (MTX) has demonstrated significant activity against relapsed and metastatic osteosarcoma. However, there is little published data to indicate the appropriate dose for MTX when given as a component of a multidrug regimen for the treatment of osteosarcoma. Therefore, the investigators at the Childrens Cancer Study Group undertook a randomized clinical trial that compared Adriamycin and vincristine given with either high-dose methotrexate or moderate-dose methotrexate as postoperation chemotherapy in the treatment of childhood osteosarcoma. We report here the results for 166 patients with completely resected nonmetastatic disease of an extremity. The two therapies demonstrated equivalent disease-free survival (DFS). Further, no therapy prejudices survival after relapse. Approximately 38% of patients remain disease free 4 years after diagnosis. Two relapses occurred in patients free of disease at least 36 months after initiation of treatment. Some factors found by other investigators to be prognostic of poorer DFS, namely, male sex, primary tumor in the humerus or femur, and larger primary tumors, demonstrated similar though not statistically significant trends. The presence of spontaneous necrosis in the tumor sample from the definitive surgery was associated with poor prognosis for DFS. We postulate that this feature represents rapidly growing tumors with increased potential for metastases.
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PMID:A randomized study comparing high-dose methotrexate with moderate-dose methotrexate as components of adjuvant chemotherapy in childhood nonmetastatic osteosarcoma: a report from the Childrens Cancer Study Group. 329 1


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