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)

Cis-diamminedichloro platinum (II) (cis-DDP) and cis-diamminediaquo platinum (II) nitrate (cis-aq) were complexed to a macromolecular carrier carboxymethyl dextran (CM-dex). Two carriers were used in this study, one derived from dex-T-10 (Mr-10000) and the other from dex-T-40 (Mr-40000). The two platinum (II) drugs formed soluble complexes with both carriers. Uncomplexed and complexed drugs were tested and found to be cytotoxic in vitro against 5 murine and 2 human derived tumor cell lines. The two free platinum (II) drugs were cytotoxic against these cells to a similar extent. In comparison to the free drugs the complexes were somewhat less active, up to 3 fold, against murine 38C-13, L1210, EL-4 and RDM-4 leukemias, as well as against human HeLa and osteogenic sarcoma, and as active as the free drugs against murine F9 embryonal carcinoma. There were no major differences in the in vitro cytotoxic activity between CM-dex T-10 and CM-dex T-40 complexes. Differences due to the molecular size of the carrier were observed in vivo: The CM-dex T-10 complexes were significantly less toxic than the free drugs, whereas the reduction of toxicity by complexing to CM-dex T-40 was less profound. As for the efficacy, when tested in vivo against a cis-DDP sensitive tumor (F9) the T-40 complexes were equally or even more effective than the respective free drugs. The T-10 complexes were less effective than the free drugs at equal drug doses but their effectivity increased at increasing drug levels. These complexes were, however, very effective in inhibiting tumor growth upon repeated injections, leading to 100% survival.
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PMID:Cis-platinum (II) complexes of carboxymethyl-dextran as potential antitumor agents. II. In vitro and in vivo activity. 243 22

Following observation of the predictive value of the histologic extent of tumor cell destruction after preoperative chemotherapy for metastasis-free survival (MFS) in osteosarcoma, a randomized study was undertaken with the aim of (1) sparing some patients the unpleasant side effects of highly toxic drugs like doxorubicin (DOX) and cisplatin (CPDD) by administering these drugs postoperatively only after poor response with a milder preoperative regimen, and (2) improving the prognosis of patients responding poorly to the initial treatment by use of a salvage chemotherapy postoperatively. The available patients were divided into two groups. Those in the study arm received a preoperative chemotherapy consisting of high-dose methotrexate (HDMTX) and the triple drug combination of bleomycin, cyclophosphamide, and dactinomycin (BCD) and were switched to DOX/CPDD postoperatively in case of poor response. DOX/CPDD was used besides HDMTX for initial treatment in the control arm, and BCD alternatively with CPDD/ifosfamide (IFO) for postoperative salvage treatment. The response rate of the study arm was significantly inferior to the control arm (26% v 60%; P less than .001). The actuarial 4-year MFS rate of poor responders after salvage chemotherapy also was poorest in the study arm (41%); it was unchanged in the control arm (53%) as compared with that of poor responders from the COSS-80 study without salvage chemotherapy (52%). The actuarial 4-year MFS rate of good responders was 73% in the study arm, 79% in the control arm, and not significantly different from that of the COSS-80 study (84%), although postoperative chemotherapy of good responders had been markedly shortened as compared with the COSS-80 study. The actuarial 4-year MFS rate of the study arm as a whole was inferior to that of the control arm (49% v 68%; P less than .1) and also inferior to the COSS-80 study (68%; P less than .01), indicating a failure of the employed salvage strategy in general and especially of the effort to restrict the use of the very effective but highly toxic drugs DOX and CPDD to patients resistant to a less toxic initial treatment.
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PMID:Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response. 244 28

Cisplatin was used in 14 bone and soft tissue sarcomas. Severe vomiting developed in all cases, but the duration was relatively short. Renal function was disturbed in cases with a higher total dose. This side effect was considered to be the dose-limiting factor of cisplatin. Seven cases showed high-frequency deafness but they did not complain of disturbance during conversation. In seven metastatic osteosarcomas, one was evaluated as a partial response and one as a minor response. No response was observed among three soft tissue sarcomas. Three cases of osteosarcoma receiving cisplatin in adjuvant chemotherapy have been disease-free for 4 and 46 months after resection of pulmonary metastases and for 50 months after resection of the primary tumor. We consider cisplatin to be the first-choice drug in cases resistant to adriamycin or methotrexate, but there are some problems when cisplatin is used in adjuvant chemotherapy, because of its side effects.
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PMID:[Chemotherapy using cisplatin in bone and soft tissue sarcoma]. 346 52

The effectiveness of cis-diammine-dichloroplatinum (cisplatinum, platidiam, DDP) alone or as a component of combined treatment was evaluated in 85 patients with osteogenic sarcoma. The said drugs were used as adjuvants following radical surgery (group I-18 cases), in combined treatment of solitary and single lung metastases (group 2-7 cases) and in 60 patients with advanced tumors (group 3). An analysis of long-term results showed response in 30.8% in group 3. In group 2, application of chemotherapy plus surgery was followed by remissions of 2-46+-month duration (mean-13.9 months). In group I, 78.7% are expected to survive metastasis-free more than 12 months. Toxicity was moderate, with nausea and vomiting (87.1%), myelosuppression (52.8%), nephrotoxicity (48.6%) and alopecia (75.7%) being the most common side-effects.
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PMID:[Experience with and outlook for the use of cisplatin in the combined therapy of osteogenic sarcoma]. 347 57

Eighteen children with refractory malignant tumors were treated with cis-DDP. They included 10 neuroblastomas, 2 rhabdomyosarcomas, and one each of hepatoblastoma, yolk sac tumor, osteosarcoma and pinealoma. Of 7 cases treated only with cis-DDP, 2 were NC, 6 PD and none were CR or PR. Of 11 cases treated with cis-DDP combined with other agents, 7 were PR, 2 NC, 2 PD and none were CR. The major side effect of cis-DDP was renal toxicity, but this was not serious and only transient. Three cases were treated with the continuous intra-arterial infusion method. These included 2 neuroblastomas and one yolk sac tumor. This treatment was therefore highly effective for children with malignant tumors, and few side effects were observed.
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PMID:[Effects of cis-DDP in children with refractory malignant tumors]. 395 83

Eleven patients with osteogenic sarcoma (9), Hodgkin disease (1), and mesenchymal sarcoma (1), were treated with 5-fluorouracil (5-FU) and cisplatin (DDP). Myelosuppression and vomiting of variable degrees occurred in all. No responses were seen.
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PMID:5-fluorouracil and cis-platinum in the treatment of refractory solid tumors: a pediatric oncology group phase I-II study. 694 Oct 70

A total of 114 children with solid tumors refractory to conventional therapy were evaluated for response and/or toxic effects after receiving cisplatin at doses of 3.0-4.5 mg/kg with aggressive hydration and mannitol diuresis every 3 weeks; a minimum of two courses was required for evaluation of response (110 patients). Objective responses were noted in 18 patients: rhabdomyosarcoma (three), Wilm's tumor (three), osteogenic sarcoma (three). Ewing's sarcoma (two), neuroblastoma (one), undifferentiated sarcoma (one), hepatoblastoma (one), ovarian teratoma (one), hepatocellular carcinoma (one), embryonal carcinoma of the mediastinum (one), and thymoma (one). Twenty-six patients had some evidence of renal toxicity. Asymptomatic hearing loss was commonly found when audiometry was performed (eight of 18 patients tested). Eight additional patients had symptomatic hearing problems--tinnitus or hearing loss. Myelosuppression was mild. Hypomagnesemia and/or hypocalcemia were common but only one patient had symptoms. Cisplatin, administered at a dose of 3.0 mg/kg with aggressive hydration and mannitol diuresis, is reasonably well-tolerated. Its role in the therapy for those tumors against which it shows activity remains to be determined.
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PMID:Phase II trail cisplatin in refractory childhood cancer: Children's Cancer Study Group Report. 694 56

From December 1973 to november 1978, 31 patients with osteosarcoma were treated with combination chemotherapy consisting of cyclophosphamide, vincristine, adriamycin and DTIC. 11 out of 19 patients with localized osteosarcoma are alive with no evidence of disease, 14+ to 40+ months after initiation of adjuvant postoperative chemotherapy. The probability of relapse-free survival for this group was calculated as 62% at 2 years and 48% at 3 years. Considering the 15 patients with osteosarcoma of the limbs relapse-free survival will be 79% at 2 years and 62% at 3 years. In 10 of 11 patients with no relapse the primary tumor has been located in the metaphysis of the proximal tibia or the distal femur. All patients with osteosarcoma of the trunk have died from metastases. Most of the 12 patients with metastasizing osteosarcoma died within one year after onset of chemotherapy. In none of these patients a complete remission could be achieved. For patients receiving adjuvant chemotherapy results are comparable with those reported by other investigators. In patients with disseminated osteosarcoma alternative chemotherapy regimens including adriamycin, cis-dichloro-diammine-platinum and ifosfamide may prove superior. In a pilot-study using vincristine-adriamycin-DDP or ifosfamide-DDP response to chemotherapy was noted in 4 out of 7 patients with two continuing complete remissions for 13+ and 5 1/2+ months, respectively.
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PMID:[Results of cytostatic therapy with cyclophosphamide, vincristine, adriamycin and DTIC (CYVADIC) in localized and metastasized osteosarcoma. A retrospective analysis]. 699 10

A total of 48 patients with non-metastatic osteosarcoma of the extremities were treated with a new neoadjuvant chemotherapy protocol which, prior to surgery, included the use of high dose methotrexate, cisplatin, adriamycin and ifosfamide. Cisplatin was administered intra-arterially, whereas the other drugs were given intravenously. In all of the cases response to this chemotherapy protocol was very good, allowing for conservative treatment in 46 out of 48 patients. Histological evaluation of chemotherapy response showed good (> 90%) and total necrosis in 87 and 54% of the cases, respectively. Drug toxicity was acceptable. Results were significantly better than those previously obtained in our and in other institutes when only three drugs were used (methotrexate, cisplatin, and adriamycin) in the preoperative treatment scheme. Since it has been demonstrated that grade of histological response to preoperative chemotherapy, and prognosis are closely related in osteosarcoma of the extremities treated with neoadjuvant chemotherapy, in addition to allowing for the use of conservative surgery in the majority of cases, this new protocol may also lead to a significant increase in the patient cure rate.
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PMID:Neoadjuvant chemotherapy for the treatment of osteosarcoma of the extremities: excellent response of the primary tumor to preoperative treatment with methotrexate, cisplatin, adriamycin, and ifosfamide. Preliminary results. 764 34

Human osteosarcoma cells, that were cultured to confluence and maintained under low nutrient conditions, showed potentially lethal damage repair after cisplatin treatment. This repair was inhibited by a non-toxic dose of caffeine. Flow cytometric analysis indicated that cisplatin-treated cells accumulated in the S phase by 24 hr, followed by accumulation in the G2/M phase. Caffeine inhibited the initial accumulation in the S phase and the release of cells from the G2/M block. DNA synthesis was also inhibited by the cisplatin treatment. The addition of caffeine significantly reversed this inhibition. The content of DNA-bound platinum decreased over time after cisplatin treatment. Caffeine did not influence platinum content, nor did it directly affect the DNA excision repair. Cisplatin inhibits DNA synthesis in the S phase, but caffeine reduces this inhibition. Caffeine-treated cells that pass through S phase are incapable of recovery.
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PMID:Inhibitory effect of caffeine on potentially lethal damage repair in cisplatin-treated human osteosarcoma cells. 764 67


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