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)

Children with malignancies resistant to conventional therapy were treated with cis-diamminedichloroplatinum (PDD), 15 to 20 mg/m2, given daily by rapid intravenous infusion for 5 days at 3-wk intervals. Eleven of 24 children with acute lymphocytic leukemia (ALL) received two or more courses; among these no remissions occurred. Fifty-four children with solid tumors were treated: 25 neuroblastoma, 9 rhabdomyosarcoma, 4 Ewing sarcoma, 2 testicular embryonal carcinoma, 2 retinoblastoma, and 12 miscellaneous tumors. One complete remission, 3 partial remissions, and 2 improvements were observed in children with neuroblastoma. One girl with metastatic osteogenic sarcoma achieved a partial remission. One child with metastatic testicular embryonal carcinoma showed improvement. The side effects were vomiting controlled by antiemetics in 26 children and transient elevations of serum creatinine and BUN in 14 children. Nineteen of 39 children with solid tumors, who received more than one course of PDD, had moderately severe myelosuppression caused by PDD. In summary, PDD is a promising agent in neuroblastoma, osteogenic sarcoma, and testicular embryonal carcinoma, and an ineffective agent in ALL. The effect of PDD on other types of solid tumors should be evaluated in the future.
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PMID:Cis-diamminedichloroplatinum (NSC-119875) in childhood malignancies: a Southwest Oncology Group study. 27 32

Two schedules of cis-dichlorodiammineplatinum(II) (cis-platinum) were evaluated for therapeutic efficacy and toxicity in children with malignant diseases resistant to standard therapy. Initially, cis-platinum was given as a rapid iv bolus injection at a dose of 15 mg/m2/day for 5 days every 3 weeks. The second schedule of cis-platinum was a dose of 1 mg/kg/week administered as an 8-hour infusion with mannitol. furosemide, and hydrating fluids. Using the daily schedule, no responses were seen among 23 children with acute lymphatic leukemia and only eight responses were noted among 47 children with solid tumors. Using the weekly schedule, three responses were noted among 25 children with solid tumors. Responses were observed in seven children with neuroblastoma, two with osteosarcoma, one with embryonal testicular carcinoma, and one with an endodermal sinus tumor. With one exception (a 4-year-old child with neuroblastoma), all responses were of short duration. The most common side effects with both schedules were nausea and vomiting which were usually controlled with antiemetics. The dose-limiting toxicity, especially on the 5-day schedule; was renal function impairment. Only one child who received cis-platinum weekly as an 8-hour infusion with diuresis had elevation of the serum creatinine level. Protocols are being initiated to determine the therapeutic effectiveness and toxicity of combination therapy with cis-platinum in children with neuroblastoma and osteosarcoma.
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PMID:Evaluation of cis-dichlorodiammineplatinum(II) in children with advanced malignant diseases: Southwest Oncology Group Studies. 29 82

In 22 patients with osteogenic sarcoma, treated with 103 high-dose methotrexate infusions (6-8.5 g/m2 in 4-6 h) plasma methotrexate levels were measured with a specific and rapid radioimmunoassay. Nontoxic infusions were associated with methotrexate concentrations below 8.0 X 10(-6) mol/l at 24 h, 8.0 X 10(-7) mol/l at 48 h and 4.25 X 10(-7)/mol/1 at 72 h. All patients with 48 h methotrexate levels above 1 X 10-6 mol/l manifested severe toxicity with myelosuppression and stomatitis due to delayed methotrexate excretion. Rise of serum creatinine was not reliable to predict oxicity. Determination of 48- and 72-h methotrexate concentrations proved to be a valuable method for identifying patients at high risk for toxic side effects. Additional citrovorum factor may thus be given in time.
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PMID:[High-dose methotrexate therapy in osteogenic sarcoma: plasma pharmakokinetics to predict toxicity (author's transl)]. 31 78

Sixty times of high dose methotrexate (MTX) with citrovorum factor rescue (HDMTX-CF) therapy were applied for 15 patients with osteosarcoma. The serum level of MTX was measured at every 24 hr. by FPIA (Fluorescence Polarization Immuno Assay) method and blood analysis was performed at the same time. Fourtysix parameters were measured in each HDMTX-CF therapy and examined by multiple parameter statistical analyses by a personal computer. In the results, the number of performed chemotherapy, rescue time, serum GOT and creatinine level at 24 hr. were the most relative factors for the change of serum MTX level.
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PMID:[The influence of liver and renal functions on the changes in serum methotrexate (MTX) level in high-dose MTX therapy]. 226 Aug 74

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

We measured urinary levels of total protein, N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase, and adenosine deaminase-binding protein in ten children with osteogenic sarcoma who were receiving combination chemotherapy that included 12 doses of methotrexate (12 g/m2). Analysis of the changes in these sensitive markers of renal tubular damage permitted detection of subclinical methotrexate-induced nephrotoxicity. In the absence of cisplatin, methotrexate therapy was associated with significant but transient increases in each of the four markers. Irreversible nephrotoxicity, indicated by persistent rises in NAG and alanine aminopeptidase as well as increased serum creatinine levels, was associated with doses of methotrexate that followed the administration of cisplatin (400 mg/m2). The biphasic pattern of total protein and NAG excretion observed in all patients suggests more than one mechanism of methotrexate-induced nephrotoxicity. Monitoring renal tubular damage in patients who are receiving methotrexate in combined-drug regimens would provide useful information for scheduling nephrotoxic drugs in clinical trials.
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PMID:Enhancement of methotrexate nephrotoxicity after cisplatin therapy. 287 29

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

Nineteen dogs were treated for osteosarcoma of the appendicular skeleton. Eleven dogs treated by amputation and adjunctive cisplatin chemotherapy had a significantly longer (P less than 0.003) median survival time of 43 weeks (range, 20 to 108 weeks) than did 8 dogs whose median survival time was 14.5 weeks (range, 8 to 46 weeks) after amputation alone. All 11 dogs given cisplatin were evaluated for signs of drug toxicosis. Transient episodes of vomiting were recorded in 9 of 11 dogs. Additional toxic effects included gradual decreases in endogenous creatinine clearance in 3 dogs and thrombocytopenia in 1 dog. On the basis of prolonged survival times and minimal adverse effects, we concluded that cisplatin has promise as an effective and relatively nontoxic agent, when combined with amputation, for treatment of dogs with osteosarcoma of the appendicular skeleton.
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PMID:Use of cisplatin for treatment of appendicular osteosarcoma in dogs. 316 84

We determined the risk of impaired excretion of methotrexate (MTX) in children with osteosarcoma, who also were receiving cisplatin, by analyzing urinary markers of renal tubular damage, as well as serum creatinine measured before each dose of MTX. MTX clearance was impaired in seven of the ten patients studied after cisplatin therapy. Patients with a urinary N-acetyl-beta-D-glucosaminidase (NAG) concentration of greater than 1.5 U/mmol creatinine or a greater than 50% increase in serum creatinine relative to the pretherapy level were approximately 30 times more likely to have MTX half-lives greater than 3.5 hours than were patients with lower values for these markers; MTX clearance was always impaired if both markers were elevated. If neither urinary NAG nor serum creatinine concentrations increased, the risk of impaired MTX excretion was negligible. Our findings demonstrate that urinary NAG and serum creatinine levels, measured before MTX administration, can be used to identify patients who will have difficulty in clearing the drug.
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PMID:Urinary N-acetyl-beta-D-glucosaminidase and serum creatinine concentrations predict impaired excretion of methotrexate. 347 66

A phase I study of carboplatin (CBDCA) was performed in 40 children with advanced cancer. A single course of CBDCA consisted of 4 weekly 1-hour infusions followed by a 2-week rest. The starting dose of 100 mg/m2/week was 66% of the maximum tolerated dose in adults. Escalated dose levels given were: 125, 150, 175, and 210 mg/m2. Myelosuppression was dose limiting, with thrombocytopenia more pronounced than leukopenia. There was no evidence of cumulative toxicity. The maximum tolerated dose for children with solid tumors was 210 mg/m2/week X 4. Other side effects included transient nausea and vomiting at the higher dose levels and non-dose-related, reversible changes in creatinine clearance. One patient developed hives. No hepatic toxicity was seen. Among the 28 evaluable patients with solid tumors, one of ten with osteogenic sarcoma had complete disappearance of a lung nodule for 15+ months. Two of four patients with medulloblastoma had partial responses by clinical and computerized tomographic scan for 4 and 10 months. All three responders had received prior cisplatin therapy. CBDCA has major advantages over cisplatin in terms of reduced toxicity. Responses observed in patients previously treated with cisplatin are encouraging. The recommended phase II dose for children with solid tumors is 175 mg/m2/week X 4 with a 2-week rest.
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PMID:Phase I study of carboplatin (CBDCA) in children with cancer. 352 46


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