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)

A 29-year-old patient presented with bilateral pulmonary lesions following surgery for recurrent placental site trophoblastic tumor (PSTT). On day seven after institution of the 'EMA' regimen (etoposide, medium dose methotrexate with folinic acid rescue and actinomycin-D), complete pneumothorax occurred. Closed-system air drainage brought only transient lung expansion and subsequent talc pleurodesis was needed. During follow-up, complete regression of lung metastases was observed. A literature survey of post-chemotherapy pneumothorax in patients with lung metastases disclosed fourteen hitherto reported cases. Including the present PSTT case, non-epithelial gynecologic malignancy (3 patients) ranks second to osteogenic sarcoma (6 cases) with regard to the primary tumor involved.
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PMID:Pneumothorax following induction chemotherapy in patients with lung metastases: a case report and literature review. 132 77

An 18-year-old female patient receiving adjuvant chemotherapy for osteogenic sarcoma developed a pruritic erythematous rash during infusion of the eighth dose of methotrexate (8 g/m2) in the series. In other respects, the infusion proceeded normally but the 24-hour serum concentration of methotrexate was unexpectedly and extremely high, 574 mumols/L. Dosing error was excluded, as was the hypothesis that the high concentrations were due to the presence of methotrexate-specific antibodies. Acute oliguria and renal failure were the primary manifestations of the drug-induced toxicity and the high concentrations can be attributed to decreased renal elimination of the drug over the first 24 hours. Treatment consisted of folinic acid rescue, forced diuresis, sequential charcoal haemoperfusion and haemodialysis, and repeated oral doses of activated charcoal. After examination of the contribution of the extracorporeal procedures and the charcoal to the elimination of the drug, the relative lack of morbidity was attributed primarily to the folinic acid rescue and the intensive supportive care.
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PMID:Survival after unexpected high serum methotrexate concentrations in a patient with osteogenic sarcoma. 228 98

From January 1978 to May 1983, 41 patients with primary high-grade osteogenic osteosarcoma of a limb were treated with a combination of intensive chemotherapy and prophylactic lung irradiation (PLI) intercalated between the first two cycles of chemotherapy. The primary tumor was treated according to its size and location by amputation, resection, high-dose radiotherapy, and salvage amputation for a tumor progressing under radiotherapy. Two weeks after surgery or simultaneously with radiotherapy, a three-drug regimen (cycle A) consisting of mitomycin C on day 1, vincristine followed by a 6-hour infusion of methotrexate on day 2 was given. Folinic acid rescue was started 6 hours after the end of the methotrexate infusion. A PLI of 20 G was given from day 10 to 22. On day 28, a four-drug regimen (cycle B) combining doxorubicin on day 1, vincristine on day 2 and dacarbazine with cyclophosphamide on days 3 to 6 was administered. Thereafter, five additional cycles of A and B were administered provided that the absolute number of polymorphonuclear cells and platelets had recovered. When these values were not attained, treatment was delayed until recovery. After a mean follow-up of 60.6 months, 16 patients have developed distant metastases, associated in four cases with local recurrence. Sixteen patients have died: 15 with metastases, one with no evidence of disease (toxic death). The overall survival of the entire group is 66% and the continuously disease-free survival 58% at 5 years. Alopecia, nausea, vomiting, asthenia, anorexia, and infraclinical and reversible impairment of lung ventilatory function were universal. A noticeable hematologic toxicity also was seen. One toxic death occurred after a pulmonary infection. Two patients developed cardiomyopathy. A multiparametic analysis of prognostic factors shows the very significant influence of age on treatment outcome. The continuous disease-free survival among the 17 patients younger than 15 years is 41% compared to 79% in older patients. The prognostic influence of age was independent of other factors. The delay (for more than two cycles) of methotrexate administration was the second independent prognostic factor. These results raise the question of using different protocols of adjuvant chemotherapy for patients younger or older than 15 years in order to optimize the curability/toxicity ratio.
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PMID:Age and dose of chemotherapy as major prognostic factors in a trial of adjuvant therapy of osteosarcoma combining two alternating drug combinations and early prophylactic lung irradiation. French Bone Tumor Study Group. 312 57

The pharmacokinetics of 8 g/m2 methotrexate (MTX) was compared following short (6 h) and long (24 h) infusions of the drug to 11 children with osteogenic sarcoma (OS; 42 infusion) and 28 children with acute lymphoblastic leukemia (ALL: 118 infusions), respectively. No difference was observed in the first-phase half-life, in systemic clearance or in the volume of distribution of the drug (P greater than 0.05). The concentration of MTX at the end of the infusion was approximately 4-fold higher when the drug was given over only 6 h. However, patients receiving 24-h infusions had approximately 9-fold higher levels by 24 h after the beginning of the infusion. The area under the data curve from start of the MTX infusion until the beginning of folinic acid rescue administration was significantly higher in patients with osteogenic sarcoma (6-h infusions), while the area under the log-data curve was significantly longer in the ALL group (24-h infusions) for the same period. The latter parameter is considered to be characteristic for the concentration-time-effect relationship. The longer duration of MTX administration (with delayed rescue) is thought to be more beneficial from the pharmacokinetic aspect. Patients with osteogenic sarcoma had significantly lower concentrations of MTX at the end of their last treatment with MTX than at the end of the first infusion. Patients developing MTX toxicity had shorter half-lives of MTX in the beta phase. It is suggested that cisplatin induced tubular loss of MTX and folinic acid is responsible for these observations. A wider application of clinical pharmacologic findings in the practice of the administration of cytostatics is indicated.
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PMID:Methotrexate administered by 6-h and 24-h infusion: a pharmacokinetic comparison. 326 Aug 32

A conjugate of methotrexate-substituted human serum albumin (HSA) coupled to a monoclonal antibody (791T/36) recognizing osteogenic sarcoma cell lines has been reported previously to have good cytotoxicity and specificity in vitro (Garnett et al., 1983). Cytotoxicity was assessed by the median inhibition (IC50) of [75Se]selenomethionine uptake resulting from a 24-h incubation of conjugate with antigen-bearing 788T or 791T osteogenic sarcoma cell lines. In the present work, the properties of this conjugate have been investigated to determine whether cytotoxicity is optimal with respect to binding activity, and aspects of the mechanism of action investigated by the effects of specific inhibitors of biochemical processes on conjugate cytotoxicity. Conjugate cytotoxicity was reduced by ammonium chloride suggesting that endocytosis and an acidic internal compartment were involved in the mechanism of action. The specific inhibitors of proteinases leupeptin and E64 also reduced conjugate cytotoxicity, while the inhibitors pepstatin A and chymostatin had no effect, demonstrating that cysteine proteinases were involved. The inhibitor of methotrexate transport, folinic acid, reduced the cytotoxicity of conjugate more than that of free methotrexate whereas folic acid had no effect on either, indicating that the methotrexate transport system may still be involved but in a different manner to the free drug. The cytotoxicity of these conjugates is probably near optimal for maximum selectivity.
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PMID:Studies on the mechanism of action of an antibody-targetted drug-carrier conjugate. 387 60

Twenty-nine patients with osteogenic osteosarcoma of a limb underwent both pulmonary radiotherapy and chemotherapy immediately after treatment of the primary tumor, mainly by radical surgery or radiotherapy (80 grays/tumor). Chemotherapy consisted of alternate A and B cycles every four weeks and BCG scarifications between cycles. Cycle A combines vincristine, ameticine, methotrexate and folinic acid; cycle B consists of adriamycin, vincristine, imidazole carboxamide and cyclophosphamide. A 20 gray irradiation was delivered to the thorax between the first A and B cycles. 50% of patients had no local recurrence or metastases after three years. 70% are alive at three years. Toxicity of this protocol is mainly hematologic and bronchopulmonary (with one fatal infection). Alopecia and minor digestive toxicity were recorded in all patients. Severe cardiotoxicity was seen in only one case. Longer follow-up is needed to evaluate long-term toxicity, particularly bronchopulmonary side-effects.
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PMID:[Adjuvant therapy of osteogenic osteosarcomas of the limb: results of the SO4 78 trial]. 629 Nov 57

Nine patients, aged 9 to 27 years (median 16 years), with osteosarcoma were given high-dose methotrexate followed by folinic acid rescue before amputation. The dose of methotrexate was 12 g/m2 for children under 12 years of age and 8 g/m2 for those over 12 years. Amputation was done after two to five (median four) courses of the drug. Between 5% and 60% of tumour cells were nonviable on histologic examination. No renal or hematologic toxicity was encountered. Mild mucositis and abnormal liver chemistry were present, usually after the third dose of methotrexate. Patients who achieved higher serum methotrexate levels at 24 hours after administration also had greater tumour necrosis. Postoperatively, chemotherapy was changed to cis-platinum, doxorubicin, cyclophosphamide, actinomycin and bleomycin. Seven patients finished their medication 17 to 35 months after diagnosis. One patient died after refusing chemotherapy postoperatively and another is alive with pulmonary metastases. Preoperative chemotherapy is a novel approach to the treatment of osteosarcoma and further modification of the treatment protocol may improve results.
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PMID:Preoperative administration of high-dose methotrexate for osteosarcoma. 658 72

Studies in which high-dose methotrexate (HDMTX) is used for the treatment of osteosarcoma have utilized commercial formulations of d,l-leucovorin (leucovorin calcium) for rescue from potential methotrexate (MTX) toxicity. These formulations are racemic mixtures containing equal amounts of d and l isomers of leucovorin. All of the available data indicate that the l isomer is the pharmacologically active diastereomer. A clinical study was conducted to determine if l-leucovorin was as safe and efficacious as d,l-leucovorin in the rescue of patients with osteosarcoma who were treated with HDMTX (12.5 g/m2 over 6 h). Because d,l-leucovorin consists of equal proportions of d and l isomers, l-leucovorin was administered at half the usual dose of d,l-leucovorin. In patients with delayed methotrexate excretion, l-leucovorin doses were escalated from 7.5 to 50 mg every 3 h until the MTX level was 0.3 mumol/l or less. Due to the low incidence of osteosarcoma, a control group of patients previously treated with d,l-leucovorin was utilized for comparison. Efficacy of l-leucovorin was determined by its ability to prevent HDMTX-associated toxicity. Demographic and clinical toxicity data from three patients who received 22 courses of MTX rescued with l-leucovorin were compared with data from six patients who had received 42 MTX courses rescued with d,l-leucovorin. Some liver function abnormalities and leukocyte elevations were found in both groups and were attributed to MTX administration. No clinical toxicity attributable to l-leucovorin was observed. l-Leucovorin in half the d,l-leucovorin dose was (equally) effective as a rescue treatment.
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PMID:Substitution of l-leucovorin for d,l-leucovorin in the rescue from high-dose methotrexate treatment in patients with osteosarcoma. 829 13

We report on an 18.5-year-old woman with osteosarcoma and delayed methotrexate (MTX) elimination due to renal failure after high-dose MTX, in whom rescue with high doses of folinic acid caused intolerable side effects. In this life-threatening clinical situation, the patients was rescued by the administration of recombinant carboxypeptidase G2, a bacterial enzyme that rapidly hydrolyzes MTX into inactive metabolites. This is the first report on the successful clinical use of this alternative catabolic route for the elimination of MTX.
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PMID:Successful carboxypeptidase G2 rescue in delayed methotrexate elimination due to renal failure. 851 32

Since its discovery in 1948 the clinical applications of methotrexate have widened; and in order to overcome resistances to methotrexate, the concept of high-dose methotrexate has been proposed. The use of rescue by folinic acid, as well as rapid dosage of MTX coupled with pharmacokinetic studies, have permitted us to administer an optimum dose of drug, with maximum therapeutic effects, but with reduced toxicity. Individual adaptation of posology, calculated using the test dose or according to population pharmacokinetic with a Bayesian method of parameter estimation (which allows us to adjust the dose of high-dose methotrexate during its infusion) permits control of inter and intra-individual variations of this drug. After analysis of the different methods proposed, we now present the results of 778 courses of treatment by high-dose methotrexate (while separating 238 courses for osteosarcoma as these formed a homogeneous group of patients). Theoretical maximum concentration and length of infusion were decided by physicians, followed by individual adaptation of posology by pharmacologists at the sixth hour of infusion of methotrexate. This treatment unites maximum security for the patient with no serious side effects (no grade 4 toxicity according to WHO classification), while receiving an optimum dose of methotrexate. In courses of MTX for osteosarcoma, the dose of MTX can be further intensified without risk, by administering on average 65% more than the usual dose in adults (8 g/m2) and 10% more than the usual dose in children (12 g/m2).
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PMID:[Individual dose adjustment of high-dose methotrexate in clinical practice]. 888 Dec


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