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 purpose of these studies was to determine whether chemotherapy interfered with the ability of peripheral blood monocytes from patients with osteosarcoma to respond to the liposome-encapsulated activating agent muramyl tripeptide phosphatidylethanolamine (L-MTP-PE). This was done in preparation of designing an adjuvant therapy protocol that includes L-MTP-PE combined with chemotherapy postoperatively for the treatment of primary osteosarcoma. The majority of patients who fail current adjuvant chemotherapy do so while on chemotherapy. Therefore, we believe it is important to combine L-MTP-PE with chemotherapy early in the treatment course rather than waiting until all chemotherapy cycles are completed. The tumoricidal properties of monocytes from patients with osteosarcoma could be activated by L-MTP-PE to levels equal to or greater than those expressed by normal control monocytes. No intrinsic monocyte defect could be demonstrated. Single-agent chemotherapy consisting of cisplatin (CPD), high-dose methotrexate (MTX), Cytoxan (CTX, cyclophosphamide; Bristol-Myers Co, Evansville, IN), or Adriamycin (ADR, doxorubicin; Adria Laboratories, Columbus, OH) did not interfere with this activation process. There was even a suggestion of enhanced activation potential following the administration of ADR. However, when both ADR and CTX were administered together on the same day, profound suppression in monocyte activation was observed. This suppressed function returned to normal by 3 weeks postcombination therapy. We therefore conclude that L-MTP-PE can be combined with ADR, CPD, MTX, or CTX as single agents but recommend that ADR plus L-MTP-PE is the most effective combination. By contrast, we discourage the use of L-MTP-PE when ADR and CTX are given together.
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PMID:Influence of chemotherapy administration on monocyte activation by liposomal muramyl tripeptide phosphatidylethanolamine in children with osteosarcoma. 198 74

The authors review the mean steps for the treatment of osteogenic osteosarcoma from the 1970's: 1), demonstration of the effectiveness of HDMTX and possibility of weekly administration, dose-response effect, interest of other drugs (BCD, ADR, CDDP, IFX); 2), use of the primary as chemosensibility witness; 3), extent of conservative surgery. In order to optimize the good results obtained by Rosen (more than 80% DFS at 5y) the authors studied the HDMTX pharmacokinetics, the value of the seric peak at the end of infusion as an effective test and individualized the HDMTX treatment in each patient following his own pharmacokinetics. This individual approach allows us to obtain more than 90% actuarial event-free survival at 4 years in patients treated by conservative surgery.
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PMID:Osteogenic osteosarcoma: a model of curable disease by multidisciplinary approach of treatment. 209 6

Ninety-eight pediatric patients were treated with three separate protocols (Treatment and investigation of Osteosarcoma [TIOS] I, II, and III) and 47 developed recurrent disease (metastases and/or local recurrence). Actuarial overall disease-free survival (hereafter designated survival) was 43%. Over 90% of the patients were treated initially with preoperative intraarterial cisplatin (CDP). Postoperative chemotherapeutic regimens comprised high-dose methotrexate with leucovorin rescue (MTX-CF), Adriamycin [( ADR] doxorubicin; Adria Laboratories, Columbus, OH), and cyclophosphamide. Primary definitive treatment comprised amputation or limb salvage (TIOS I and TIOS III). Patients treated with preoperative CDP and surgery (TIOS I and III) had a 62% survival. Patients in TIOS II refused surgical extirpation; they were treated exclusively with chemotherapy and had a 23% survival. Survival in patients treated with amputation was 55% and limb salvage 58%. Prognostic factors considered significant in relation to development of pulmonary metastases comprised tumor burden (P = .04) and the percentage of tumor necrosis induced by preoperative chemotherapy (P = .01). Histopathologic subtype was marginally significant: chondroblastic was more favorable as opposed to osteoblastic (P = .05). These findings are compared with results and prognostic factors published in the literature.
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PMID:Pediatric osteosarcoma: therapeutic strategies, results, and prognostic factors derived from a 10-year experience. 223 Aug 90

Local response of hyperthermia for soft tissue and bone tumors was investigated. Ten tumors were superficial tumors and 16 were deep seated tumors; 9 tumors were malignant fibrous histiocytoma, 5 were liposarcoma, 4 were neurogenic and 3 were myogenic sarcoma. The other five tumors were an angiosarcoma, a malignant mesenchymoma, an Ewing's sarcoma, a chordoma and an osteosarcoma. Some 23 tumors were heated in combination with radiation therapy, and 3 were combined with arterial infusion of ADR. Four of 10 superficial tumors disappeared (CR), and, 2 of 10 signified PR. Only one of 16 deep seated tumors showed CR, 3 were PR and 12 showed no response. But 4 of 12 tumors without regression in tumor volume indicated coagulation necrosis owing to histological examinations, and 5 of 12 were regarded as the same response from hypodensity area with CT examination after hyperthermia. Local response rate of of superficial tumors was 60% and that of deep-seated tumors was 81.4%.
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PMID:[Hyperthermia in bone and soft tissue tumors]. 283 94

Adjuvant chemotherapy mainly with ADR performed in 117 patients (pts) with primary osteosarcoma of the extremity for the purpose of preventing pulmonary metastasis after radical ablative surgery. The mean follow-up period for 117 pts was 51.7 months (range: 3 to 137), for 53 survivors, 90.1 months (range: 60 to 137) and for 64 decreased, 20.5 months (range: 3 to 73). ADR was administered intravenously with 0.6-0.8 mg/kg/day for 3 consecutive days at monthly intervals after surgery until reaching 600 or 500 mg/m2 of the total cumulative dose. Five-year overall and disease-free survival rate of all pts was 50.2% and 39.4%, respectively. Thirty-seven pts (multi-drug group) with the combination of ADR and HDMTX had a higher survival rate (63.1% in 5-year overall survival rate and 47.8% in 5-year disease-free survival rate) than that of 80 pts with ADR alone (ADR group) (44.4% in 5-year overall survival rate and 35.6% in 5-year disease-free survival rate). Five-year survival rate for 65 pts administered the greater than 500 mg of ADR was 59.3% compared to 36.9% for 52 pts the less than 500 mg (p less than 0.05). In 65 pts administered the greater than 500 mg of ADR, 5-year survival rate (76.5%) of the multidrug group (17 pts) showed superiority to that 52.1%) of the ADR group (48 pts) (p less than 0.01). Even in the multi-drug group, 5-year survival rate (76.5%) of 17 pts administered the greater than 500 mg of ADR was higher than that (41.3%) of 20 pts given the less than 500 mg (p less than 0.01). Distant metastases were recognized at lung in 52 pts (lung group), lung + extrapulmonary organs in 14 (+ extragroup), and only extrapulmonary organs in 3 (extra group). Five-year survival rate of 66 pts with pulmonary metastasis was 17.1% and 21.2% in the lung group compared with 0% of the extra group (P less than 0.01). Five-year survival rate for 23 pts treated with thoracotomy was 43.5% compared to 2.6% for 43 without it (p less than 0.01).
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PMID:[Evaluation of adjuvant chemotherapy of osteosarcoma with special reference to adriamycin (final report)]. 319 42

The authors evaluated a new protocol of neoadjuvant chemotherapy for osteosarcoma, easier to manage and different from T10. The good results obtained with the postoperative ADR-CDDP association led us to undertake a pilot study between 1982 and 1984, using ADR-CDDP as preoperative chemotherapy. The records of sixteen patients were available for follow-up. The average age of the patients was 19.9 years. Patients received two or three preoperative courses, and a total of six identical courses. Tolerance was good. Pain usually disappeared but this was often misleading because associated with radiological and/or clinical tumor progression, low histological necrosis or poor outcome. The continuous disease-free survival actuarial rate was less than 57 and 40% at 18 months and two years respectively. The actuarial survival rate was 87% at one year and 65% at two years respectively. Disappointing results of this preoperative protocol, compared to results with the SO4 78 or T10 protocols for example, led to publish these data early in order to underline their potential dangers. As a result, we stopped our study. The charter of pilot studies justifies this publication. As well, these data point out the necessity of very close follow-up of neoadjuvant chemotherapy by sophisticated medical imaging. Neoadjuvant chemotherapy, if ineffective, must be stopped early, and should lead to surgery, followed by adequate postoperative chemotherapy.
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PMID:[Pre and postoperative chemotherapy of osteosarcoma with an adriamycin-cisplatin combination. Risks of a neoadjuvant chemotherapy which is not sufficiently effective]. 346 71

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

A study on the effect of anti-tumor agents combined with caffeine on sarcoma cells was carried out by clonogenic assay. The materials used were an established line of human osteosarcoma cells (OST strain) and twelve surgically resected or biopsied specimens. Caffeine showed a marked synergistic effect on sarcoma cells with the DNA-damaging agents, ADR, CDDP, CPM and MMC in terms of colony inhibition. In particular, 0.2 micrograms/ml CDDP with 2 mM caffeine showed a considerable synergistic effect on human sarcoma cells. Among the 12 cases, more than 50% colony inhibition was observed in 7 cases which were treated with this combination of CDDP with caffeine. Furthermore, a combination of 0.02 micrograms/ml CDDP (1/100 of peak plasma concentration) with 2 mM caffeine also showed more than 50% colony inhibition. Therefore, we assumed that caffeine was able to reduce the necessary dose of anti-tumor agent in some way. We stress that caffeine seems to be a very useful synergistic drug for causing lethality in sarcoma cells in combination with various DNA-damaging agents which are not effective on sarcoma cells.
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PMID:[A study of the effect of anti-tumor agents combined with caffeine on established lines of human osteosarcoma cells and primary cultured human sarcoma cells by clonogenic assay]. 347 41

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

CI-994 [aka: acetyldinaline; PD 123654; 4-acetylamino-N-(2'aminophenyl)-benzamide] (Figure 1) is a novel antitumor agent with a unique mechanism of action. It is the acetylated metabolite of dinaline, a compound previously identified as having cytotoxic and cytostatic activity against several murine and human xenograft tumor models. CI-994 had activity against 8/8 solid tumors tested (log cell kills at the highest non-toxic dose): pancreatic ductal adenocarcinoma #02 (4.7); pancreatic adenocarcinoma #03 (3.0; 1/6 cures); colon adenocarcinoma #38 (1.6); colon adenocarcinoma #51/A (1.1); mammary adenocarcinoma #25 (1.7); mammary adenocarcinoma #17/ADR (0.5); Dunning osteogenic sarcoma (4.0); and the human prostate carcinoma LNCaP (1.2). CI-994 had the same spectrum of activity in vivo as dinaline. It also behaved similarly in schedule comparison/toxicity trials. Prolonged administration with lower drug doses was more effective than short-term therapy at higher individual doses. If doses were kept between 40 and 60 mg/kg/injection, prolonged administration (> 50 days) was tolerated with no gross toxicity. Doses > or = 90 mg/kg/injection caused lethality after 4-5 days of administration. The maximum tolerated total dose was also increased with smaller individual doses administered for prolonged intervals. Clinical Phase I trials are ongoing with this agent.
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PMID:Preclinical antitumor activity of CI-994. 915 69


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