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)

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

The neoadjuvant study COSS-86 was undertaken aiming at (1) improving the cure rate in osteosarcoma by early intensification of chemotherapy in high risk patients and (2) investigating the effect of intraarterial (i.a.) versus intravenous (i.v.) administration of cisplatinum. (1) Ifosfamide was added to the well proven drugs in osteosarcoma such as doxorubicin, high-dose methotrexate and cisplatinum in patients with large tumor size or/and high portion of chondroid groundsubstance or/and scintigraphic nonresponse after 4 weeks of preoperative chemotherapy. It was given in combination with cisplatinum. (2) The same patients were allocated to either the intraarterial study arm or the intravenous control arm of the study. The response rate (greater than 90% tumor necrosis) of all patients was 75% (88/118). No advantage in response rate was achieved by i.a. infusion of cis-platinum within this highly efficient 4-drug regimen (i.a. 75% (33/44) vs. i.v. 74% (35/47)). The significantly improved response rate in this study results in a better metastasis free survival (MFS) of 77% (+/- 4) at 4 years.
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PMID:[Neoadjuvant chemotherapy of osteosarcoma. Preliminary results of the cooperative COSS-86 osteosarcoma study]. 194 29

Ifosfamide is an analogue of cyclophosphamide that has been extensively investigated in sarcomas. Like doxorubicin and dacarbazine, it belongs to the class of drugs active against advanced soft tissue sarcomas; its optimal use in combination regimens has not been identified. In the treatment of osteosarcoma and Ewing's sarcoma, ifosfamide has been identified as an effective drug. Nonetheless, in these diseases, too, its optimal place in combination therapy has not yet been determined.
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PMID:The role of ifosfamide in the treatment of adult soft tissue sarcomas, Ewing's sarcoma, and osteosarcoma: a review. 218 47

A phase-II study of ifosfamide with mesna, given intravenously daily for five days by bolus injection, has demonstrated the activity of ifosfamide against a spectrum of childhood malignant solid tumors. Ifosfamide presently is being investigated in alternative phase-I schedules, daily times three or every other day times three with the aim of delivering comparable amounts of ifosfamide without increasing toxicity--specifically, neurotoxicity. Additionally, response following ifosfamide treatment is being evaluated for previously untreated children with osteosarcoma and rhabdomyosarcoma after 6 weeks of treatment, and for previously untreated patients with Ewing's sarcoma after 9 weeks of treatment with ifosfamide/VP-16 (etoposide) given in combination.
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PMID:Clinical studies of ifosfamide/mesna at St Jude Children's Research Hospital, 1983-1988. 249 67

Ifosfamide/mesna was given to 97 patients who had malignant solid tumors diagnosed before they were 21 years of age. Patients received 1.6 g/m2 ifosfamide daily x 5, given i.v. over 15 min, followed by 400 mg/m2 i.v. mesna at 15 min and 4 and 6 h after ifosfamide. Responses were noted in patients with osteosarcoma, Ewing's sarcoma, rhabdomyosarcoma and other soft-tissue sarcomas, rhabdoid tumor, neuroblastoma, Wilms' tumor, primitive neuroectodermal tumor, retinoblastoma, germ-cell tumors, and B-cell lymphoma. Toxicity included mild to moderate nausea and vomiting, transient, reversible myelosuppression, transient elevations of serum blood urea nitrogen (BUN) and creatinine and liver enzymes, infections, and self-limiting neurotoxicity characterized by changes in mental status, motor dysfunction, cranial nerve palsy, cerebellar dysfunction, and seizures. Neurotoxic symptoms were generally seen in patients who had previously received cisplatin. Ifosfamide is an important alkylating agent that should be combined with other agents in phase II and III trials. Alternate dose schedules should also be investigated.
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PMID:Ifosfamide in pediatric malignant solid tumors. 250 57

Ifosfamide was given to 61 patients with malignant solid tumors diagnosed before the age of 21 years. In this phase II study, all patients received 1.6 g/m2/day X 5 iv over 15 minutes followed by mesna at a dose of 400 mg/m2 iv at 15 minutes and 4 and 6 hours after ifosfamide. Responses were observed in five of 15 patients with osteosarcoma, two of ten with neuroblastoma, two of six with Wilms' tumor, two of five with rhabdomyosarcoma, four of eight with other soft tissue sarcomas, one of one with retinoblastoma, one of two with germ cell tumors, one of one with B-cell lymphoma, and one of one with a primitive neuroectodermal tumor. Fifty-nine of 61 patients had received prior alkylating agent therapy which included cyclophosphamide, cisplatin, mechlorethamine, melphalan, or dacarbazine. Fourteen of 19 responses developed in patients whose tumors were resistant to treatment with cyclophosphamide. A patient with malignant Schwannoma who had received no prior chemotherapy developed a complete response which lasted 12 months. A patient with brain metastases of osteosarcoma has had complete response for greater than 2 years. Complete response was also observed in a patient with B-cell lymphoma. Toxicity consisted of mild to moderate nausea and vomiting, transient reversible myelosuppression, occasional elevation of serum BUN or creatinine, and transient neurotoxicity characterized by somnolence, confusion, weakness, tremor, hallucinations, or seizures. We conclude that ifosfamide is an important alkylating agent without apparent complete cross-resistance with cyclophosphamide, and as such should be further investigated for determination of its activity in patients with pediatric neoplasms and considered for incorporation into phase II-III trials for certain tumors.
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PMID:Phase II trial of ifosfamide in children with malignant solid tumors. 310 34

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

We have evaluated the activity of ifosfamide in 75 patients with recurrent sarcomas and pediatric solid tumors. All patients had previously received cyclophosphamide in combination with other chemotherapeutic agents. Ifosfamide was administered as a continuous 5 day infusion at a dose of 1800 mg per M2, except in the last 14 patients who received the drug as a daily one hour infusion at the same dose level. Partial response was observed in 9 of 20 patients with Ewing's sarcoma, 2 of 9 patients with rhabdomyosarcoma, 3 of 17 patients with osteogenic sarcoma and 4 of 29 patients with various other neoplasms. A further 6 patients had stable disease, defined as the absence of progression for at least 6 cycles of therapy. Thus overall response rate was 24%, with the highest response rate of 45% being observed in Ewing's sarcoma. Toxicity was acceptable, although there was quite marked leucopenia (median nadir 700) with less profound thrombocytopenia (median nadir 87,000). Sepsis occurred in 3 patients but no patient died as a result of infection. Hematuria occurred in 43% of patients who did not receive mesna, and in 26% of patients who did, although prior pelvic irradiation was found to be a significant risk factor for hematuria. Only 1 of 14 patients without prior pelvic irradiation or hematuria developed hemorrhagic cystitis when treated with ifosfamide and mesna. Confusional states developed in 6 patients. We conclude that ifosfamide is an active agent in patients with relapsed sarcomas and childhood solid tumors, even when such patients have been previously treated with cyclophosphamide.
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PMID:A phase II study of ifosfamide in the treatment of recurrent sarcomas in young people. 381 17

Ifosfamide given to 42 patients iv at 2-2.5 g/m2/day X 4 resulted in partial responses in ten of 28 (36%) evaluable patients with adult soft tissue sarcomas, including two of two with chondrosarcoma; none of nine with pediatric sarcomas (Ewing's sarcoma, osteogenic sarcoma, or rhabdomyosarcoma) achieved partial response. All of the pediatric patients had failed to respond to complicated three- to six-drug regimens of up to 18 months in duration. The response rates in patients with and without prior cyclophosphamide (32%; seven responses among 22 patients; and 20%, three responses among 15 patients) were not significantly different, supporting in vitro evidence of a lack of cross-resistance between the two related compounds. Myelosuppression was dose-limiting. Hemorrhagic cystitis was not observed in patients treated with 400-500 mg of mesna iv every 4 hours during ifosfamide treatment. Nausea and vomiting were generally mild or moderate. Alopecia was universal but reversible. Of the first 11 patients, five became somnolent or developed visual hallucinations (during six of the 12 total courses administered to the five patients). Only one patient had two episodes of neurotoxicity. After reduction of the use of iv antiemetics and major narcotics, single episodes of neurotoxicity were seen in five of the next 27 patients. An asymptomatic acidosis developed in most patients, requiring bicarbonate replacement in one. Ifosfamide appears to be active in previously treated patients with sarcomas and should be evaluated in patients with less extensive prior treatment.
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PMID:Phase II trial of ifosfamide with mesna in previously treated metastatic sarcoma. 392 1


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