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)

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

The cytostatic action of Adriblastin on the accumulation of 99mTc-MDP by a transplantable osteogenic sarcoma in the mouse was investigated. The quantitative determination of the activity concentration in the tumor showed a concentration value 8 days after the administration of the cytostatic which was nearly twice that found in the untreated animals. This could be clearly observed in scintigrams obtained with a gamma-camera using a pinhole-collimator. The histoautoradiography likewise showed a higher concentration of the radiopharmaceutical which can be attributed to higher ossification within the tumor due to the application of the cytostatic agent. Our results indicate that scintigraphy with 99mTc-MDP is a good follow-up method during treatment with cytostatics.
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PMID:[The effect of chemotherapy on the retention of 99mTc-methylenediphosphonate by the osteogenic sarcoma of the mouse (author's transl)]. 693 74

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

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

Osteosarcoma is one of the most common juvenile malignant tumors in Korea. Combined modality treatment (pre-operative chemotherapy + limb salvage surgery + adjuvant therapy) improved the patients' overall survival and quality of life. We evaluated the efficacy and feasibility of pre-operative chemotherapy with intra-arterial (IA) cisplatin plus continuous intravenous infusion (CI) of adriamycin. We assessed the rate of limb salvage, recurrence pattern and the survival impact based on the histologic response of pre-operative chemotherapy. Fourty-one patients with histologically-proven high grade osteosarcoma of the extremities were enrolled from January 1990 to June 1995. Pre-operative chemotherapy, cisplatin 120 mg/m2 IA and adriamycin 75 mg/m2/72 h CI was administered every 3 weeks for 3 cycles, followed by limb salvage surgery if possible or by amputation. According to the histologic tumor response, if the tumor necrosis was >90%, the same regimen was administered for 3 cycles as an adjuvant therapy. A salvage regimen (Ifosfamide 7.5 gm/m2/5 d IV + high dose MTX 10 gm/m2 IV+VP-16 360 mg/m2/3 d IV) was administered every 3 weeks for 6 cycles if the tumor necrosis was <90%. Of 41 patients, 37 patients were evaluable for efficacy and toxicities, because 4 patients refused chemotherapy after 1 or 2 cycles. Twenty-one patients were male and 16 were female with median age of 16 years (range 8-41). The tumor locations were: distal femur 20, proximal tibia 8, humerus 6, distal tibia 2 and 1 in proximal femur. All but one patient, who died of neutropenic sepsis, completed the planned pre-operative therapy. Of the 36 patients who received surgery, limb salvage surgery was possible in 30 patients (83.3%) and 27 patients (75%) showed a good response (grade III 10; 27.8%, grade IV 17; 47.2%). With a median follow-up of 23 months, 3-year disease-free survival rate was 54.7% and overall survival rate was 78.3%. Of the 15 patients who recurred, the major metastatic site was the lung. No operation-related mortality was observed. Most patients experienced grade III-IV nausea, vomiting and hematologic toxicities, which were reversible with supportive cares. Pre-operative chemotherapy with IA DDP+CI ADR followed by surgery showed 75% histologic tumor response rate, 83% limb salvage rate and 54.7% 3-year disease-free survival rate with tolerable side effects. To improve the survival rate, the possible role of good salvage chemotherapy with a non-cross resistance regimen in poor responders should be evaluated.
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PMID:Combined pre-operative chemotherapy with intra-arterial cisplatin and continuous intravenous adriamycin for high grade osteosarcoma. 1020 5

Neoadjuvant chemotherapy plays a significant role in improving the prognosis of malignant bone tumors such as osteosarcoma and Ewing's sarcoma. Doxorubicin, cisplatin and high-dose methotrexate are key drugs in the chemotherapy for osteosarcoma. Intraarterial administration of the drugs is very effective in local control, so that wide resection of the tumor may be performed safely. The efficacy of preoperative chemotherapy is evaluated by the histological necrosis rate of the resected tumor after which postoperative drugs will be chosen. Limb salvage is becoming more and more common, and an excellent limb can be reconstructed using an artificial joint. In soft tissue sarcomas, brachytherapy can make the surgical resection margin narrower, resulting in good function of the extremities. Fragility of bone caused by metastatic bone diseases is reversed by surgical intervention.
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PMID:[Recent advances in management of musculoskeletal tumors]. 1041 Jun 73


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