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-Dichlorodiammineplatinum(II) (cis-platinum) has no more than additive, and often much less than additive, lethal toxicity for mice when given in combination with other anticancer agents representing several of the major functional classes of clinically useful anticancer drugs. The previously reported broad spectrum of anticancer activity of cis-platinum against tumors in laboratory animals has now been extended to promisingly useful therapeutic synergism in combination with other active anticancer drugs, including advanced-staged tumors in mice; eg, cis-platinum plus cyclophosphamide against advanced Ridgway osteogenic sarcoma and advanced P388 leukemia, and as surgical adjuvant chemotherapy against advanced colon tumor 26; cis-platinum plus Adriamycin against advanced P388; and cis-platinum plus VP-16-213 against advanced P388. Therapeutic synergism was also seen with cis-platinum plus carminomycin (an Adriamycin analog) against early colon tumor 26. Resistance and cross-resistance studies using sublines of L1210 and P388 selected for resistance to various alkylating agents (cyclophosphamide, melphalan, BCNU, or cis-platinum) indicate a variety of resistance and cross-resistance patterns which further support the growing body of evidence that wide differences in mechanism of cytotoxic activity exist among alkylating agents having experimentally and clinically useful anticancer activity. These data support the observed therapeutic synergisms with combinations of alkylating agents seen against a broad spectrum of murine tumors, and they suggest other drug combinations that might be considered for experimental and clinical trial based on a growing number of logical differences in biochemical mechanism of action of alkylating agent anticancer drugs that have been reported.
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PMID:cis-Dichlorodiammineplatinum(II): combination chemotherapy and cross-resistance studies with tumors of mice. 29 80

cis-Dichlorodiammineplatinum(II) (cis-platinum) was evaluated in three separate studies at Roswell Park Memorial Institute in children and adolescents with cancer. In the first study, 16 patients with a variety of solid tumors were treated. Objective responses were seen in patients with neuroblastoma, osteogenic sarcoma, seminoma, and medullary carcinoma of the thyroid. In the second study, five of eight patients with far-advanced osteogenic sarcoma showed objective responses to cis-platinum. In the third study, cis-platinum and Adriamycin were employed as primary adjuvant chemotherapy along with surgery in osteogenic sarcoma. Nine of ten patients have remained disease-free from 8 to 31 months (mean, 19 months). cis-Platinum is an active agent in pediatric tumors.
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PMID:cis-Dichlorodiammineplatinum(II) in childhood cancer. 29 83

cis-Dichlorodiammineplatinum(II) (DDP) was studied in 16 children with far-advanced malignancies. Three dosage schedules were tried: regimen A, 20 mg/m2/day x 5 days for 3-4 weeks (11 patients); regimen B, 50 mg/m2 once a week (four patients); and regimen C, 60 mg/m2/day x 2 days every 3-4 weeks (one patient). Four of 16 patients (25%) showed partial response, including one with osteogenic sarcoma, one with neuroblastoma, one with seminoma, and one with medullary carcinoma of the thyroid. Two patients showed clinical improvement. The major toxic manifestations included nausea and vomiting (16 of 16), renal toxicity (three of 16), transient pancytopenia (six of 12), and hearing loss (two of 16). It is apparent that DDP has activity in pediatric tumors; however, a more precise response rate must be delineated in a larger series of patients.
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PMID:Clinical response and toxicity with cis-dichlorodiammineplatinum(II) in children. 89 Jun 92

We attempted to ascertain renal, hematologic, and neurologic tolerance to ifosfamide (IFX) in pediatric patients previously treated with large single and cumulative doses of cis-Diamminedichloroplatinum-II (CDP) for osteosarcoma (OS). Twenty OS patients were treated with CDP: initially 150 mg/m2 was administered every 2 weeks for a maximum of seven courses. Later, other agents, including additional CDP, were also administered. Twelve patients were treated with intra-arterial CDP, one with intra-arterial, and later intravenous CDP, and seven with intravenous CDP. Patients who relapsed were treated with IFX. Renal function was monitored by measuring creatinine clearance, serum electrolytes, total protein, albumin and CO2 content, and urine analysis during IFX therapy. Prior to initiation of IFX, creatinine clearance was above 60 ml/min/m2 in all except one patient who had developed a hemolytic uremic syndrome (HUS). Cumulative CDP doses ranged from 300 to 22,500 mg/m2, and cumulative IFX doses 12 to 128 gm/m2. Myelosuppression was monitored by obtaining routine hemograms midway between each course of treatment. Neurologic tolerance was assessed by reviewing the medical records for any abnormality. The interval between CDP and IFX ranged from 1 to 64 months. All patients experienced a progressive reduction in creatinine clearance with CDP. The reduction in creatinine clearance, measured from base-line after three to four courses varied from 10 to 53.7%, after four to seven courses from 19 to 78%, and after seven courses from 12 to 80.5%. In all patients except five, including the HUS patient, creatinine clearance remained above 60 ml/min/m2 during IFX therapy. Twelve patients developed hypo-magnesemia in the vicinity of 1.4 to 1.6 mg/dl during CDP treatment and required magnesium supplementation. They were asymptomatic and the abnormality did not affect IFX tolerance. Fourteen patients intermittently displayed variable degrees of glycosuria, phosphaturia, and/or proteinuria during IFX therapy. This was considered to be a forma frustre type of Fanconi's syndrome. Approximately 80% of courses of IFX were associated with reversible myelosuppression. No neurologic abnormalities were detected. The abnormalities detected during IFX treatment were not major, did not give rise to symptomatology, and did not require discontinuation of therapy. Renal abnormalities were considered a forma frustre type of Fanconi's syndrome. Provided a creatinine clearance of 60 ml/min/m2 is accepted as a prerequisite for treatment, and no major preexisting renal disease is present, IFX is well tolerated by most patients previously exposed to very high cumulative doses of CDP.
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PMID:Ifosfamide tolerance in osteosarcoma patients previously treated with cis-diamminedichloroplatinum-II: renal, hematologic, and neurologic observations. 749 10

Intravenous cis-Diamminedichloroplatinum-II (CDP) was administered to 10 patients with osteosarcoma to treat the primary tumor in 8 and bone metastases in 2. Three patients also had pulmonary metastases. The intent was to deliver 7 courses (150 mg/M2 q 2 weeks) over 3 months (total cumulative dose 1050/mg/M2). However, this was only accomplished in 2 patients; in the remaining 8 the full course was not administered because of temporary renal insufficiency (3), tumor escape (1) and apparent response after 4-6 courses suggesting that no further benefit would accrue (4). Overall, clinical and/or radiologic responses were observed in 9 patients. In 6 of 9 tumors subjected to surgical resection (66%), necrosis in excess of 65% was observed. Optimum results were achieved with a cumulative dose of 600 mg/M2 administered over 6 weeks. These results suggest that intravenous CDP may be as efficacious as intra-arterial CDP which has produced similar responses.
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PMID:Pediatric osteosarcoma - treatment of the primary tumor with intravenous cis-diamminedichloroplatinum-ii (cdp) - comparison of the results with the reported efficacy of intraarterial cdp. 2157 59