Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper evaluates the influence of pharmacokinetics monitoring of HDMTX in the treatment of localized operable previously untreated high grade osteosarcoma. 44 patients (group 1) received a T10 protocol with dose adapted only to age. 27 other patients (group 2) had a pharmacokinetics monitored dose adaptation of MTX. The pharmacokinetics monitoring leads to higher dosage, higher area under the concentration/time curve and permits higher toxicity to be avoided. The higher dose intensity of MTX gave higher histologic response rate (66% compared to 45%) and higher 5 year disease free survival (92% compare to 76%). HDMTX treatment of osteosarcoma should be dose adapted to indivi-dual pharmacokinetics.
 ...
PMID:Dose escalation with pharmacokinetics monitoring in methotrexate chemotherapy of osteosarcoma. 776 28

Temporary neurologic abnormalities were observed in one out of 23 patients undergoing chemotherapy with high-dose methotrexate (HD-MTX) for osteogenic sarcoma. This patient developed sequential symptoms including alternative hemiparesis, dysarthria and altered consciousness 5 days after the second course of HD-MTX (8 gm/m2 by 6 h continuous infusion) with leucovorin rescue. Laboratory evaluations disclosed normal electrolytes, hemograms and non-toxic serum MTX levels at the onset of the symptoms. Computed tomography of the brain was normal but electroencephalography showed focal theta and delta slow waves over the right temporal-parietal-occipital area. The neurological symptoms resolved completely within 72 h.
 ...
PMID:Transient neurological disturbances induced by the chemotherapy of high-dose methotrexate for osteogenic sarcoma. 794 55

A retrospective investigation was performed on the significance of dose intensity in preoperative chemotherapy for osteosarcoma. In this paper, we studied 29 patients, who had classical stage II-B osteosarcoma and received preoperative treatment consisting of high dose methotrexate (HD-MTX) and/or cisplatinum (CDDP) between 1985 and 1991. Preoperative dose intensity was calculated in the following two ways. 1. Total dose of MTX and CDDP administered during initial five weeks: MTX (g)/10/m2 + CDDP(mg)/100/m2 2. Dose intensity of MTX and CDDP from initiation of treatment (I) to resumption of postoperative chemotherapy (R): MTX (g)/10/m2 + CDDP (mg)/100/m2 / days from (I) to (R)/ideal period of new regimen (63 days) Continuous disease free survival rate (CDFR) was significantly higher in the group receiving preoperative chemotherapy at higher dose intensity (> 3.0). Supplementary administration of adriamycin (ADR) to CDDP/MTX was not favorable in the preoperative stage, because it put off the following therapy and diminished the dose intensity. Since July 1989, we have tried a short intensive preoperative chemotherapy regimen: weekly two cycles of CDDP 100 mg/m2 intravenously, followed by weekly two cycles of HD-MTX 10g/m2. Surgery was scheduled six weeks after beginning treatment, and postoperative chemotherapy was started three weeks after surgery. Twenty patients have been treated by this regimen to date. All patients remain disease free, and six are CDF beyond 24 months.
 ...
PMID:[The importance of dose intensity in preoperative chemotherapy for osteosarcoma--retrospective analysis of a short intensive chemotherapy regimen preoperatively using high-dose methotrexate and cisplatinum]. 812 86

Therapy for osteosarcoma has changed considerably over the last two decades. We reviewed 49 cases of osteosarcoma treated in our department after 1970 and examined the present status of chemotherapy, results and the side effects. We classified the 49 cases according to treatment policy into 4 groups by age. 1) 11 cases before 1977 did not receive systematic therapy with high dose-methotrexate (HD-MTX) and such. 2) 10 cases between 1977 and 1982 were basically given HD-MTX therapy alone. 3) 15 cases between 1977 and 1982 were given preoperative HD-MTX therapy, and cisplatin (CDDP) after surgery, if necessary. 4) After 1988, patients received MTX together with CDDP before surgery and ifosfamide (IFO) or newly developed drugs, if necessary. The results for those treated after 1988 were superior to those for patients treated earlier. Further efforts to develop a more effective therapy are being made, since even present therapies have many problems.
 ...
PMID:[Chemotherapy for osteosarcoma--trends in recent years]. 821 62

Recent advances in adjuvant chemotherapy for malignant bone tumor have been improving the survival rate and making limb-salvage surgery a reliable technique. Ewing's sarcoma is treated by multiple agent chemotherapy. We treat Ewing's sarcoma by Rosen's T-11 protocol (CYT.ADM.MTX.VCR.ACT-D.BLM). This protocol is very effective, but results are poorer than for osteosarcoma. Newly developed protocols such as EICESS (European Intergroup Cooperative Ewing's Sarcoma Study)-92, including new drugs, should be investigated. The results with malignant fibrous histiocytoma are comparable to those for osteosarcoma. We have performed an original chemotherapy protocol, called "K-1 protocol." Patients were treated with three courses of intraarterial infusion of cisplatin (120 mg/m2) and caffeine (1.0-1.5 mg/m2/day for three days continuously) at two-week intervals. If the effect was insufficient, ADM (30 mg/m2/day for two days continuously) is added to this protocol. We treat malignant lymphoma in collaboration with a hematologist and radiologist. The 5-year survival rate of non-Hodgkin's lymphoma in our series was 56% in clinical stage III and 34% in clinical stage IV. We are trying third-generation chemotherapy to improve the survival rate.
 ...
PMID:[Chemotherapy for Ewing's sarcoma, malignant fibrous histiocytoma and malignant lymphoma]. 821 63

The results of two sequential studies of neoadjuvant chemotherapy for osteosarcoma of the extremities performed at Rizzoli Institute between 1986 and 1991 in 228 patients are presented. In both studies preoperative chemotherapy consisted of two cycles of high dose methotrexate (HDMTX), cisplatinum (CDP) and adriamycin (ADM). Postoperatively the good responder patients were treated with the same drugs used before surgery while in the poor responder patients ifosfamide was added to these three drugs. The preoperative treatment was the same in both studies while after surgery in the second protocol either the cumulative dose of ADM (270 mg/m2 instead of 360 mg/m2) or the single dose per cycle of this drug (60 mg/m2 instead of 90 mg/m2) was reduced. These changes in the last protocol were done to reduce the cardiotoxicity of ADM that was high in the first study (2 deaths and 1 heart transplantation). Since in the last protocol--in comparison with the first protocol--after surgery chemotherapy was restarted earlier and ADM was administered not as a single drug but in combination with the CDP the dose intensity of ADM was unchanged while the dose intensity of MTX, CDP and ifosfamide was higher than in the first study. The preliminary results of the 84 patients treated in the second study show a 2-year disease free survival significantly lower than that achieved in the 144 patients treated in the first study (37/51--73% vs 123/144--85%: P < 0.008). In addition, even if in the last study there were no cases of clinical cardiotoxicity due to ADM, there was a significantly higher percentage of severe myelodepression that led to two deaths for infectious complications. These results suggest that in neoadjuvant treatment of osteosarcoma the total dose of ADM and/or the single dose per cycle of the same drug are an important determinant of outcome and that increasing the dose-intensity of less toxic but less active agents, MTX, CDP and ifosfamide, at the expense of the more active and more toxic agent, ADM, can lead to a poorer outcome without reducing toxicity.
 ...
PMID:Influence of adriamycin dose in the outcome of patients with osteosarcoma treated with multidrug neoadjuvant chemotherapy: results of two sequential studies. 822 52

One of the major complications after high-dose methotrexate (HDMTX) infusions is renal damage. We investigated the occurrence of proteinuria after HDMTX administration in children with pediatric malignancies (acute lymphoid leukaemia, osteosarcoma Burkitt's lymphoma). In the period 1989-1990 we gave 52 HDMTX courses to 24 children. During this period, prehydration and extra urinary alkalisation were performed only if the urinary specific gravity was over 1010 or if the urinary pH fell below 7. Using this schedule the mean values obtained for protein extraction were: before the therapy, 0.12 +/- 0.03 g/m2; on day 1 after MTX treatment, 0.38 +/- 0.06 g/m2; and on day 2 after the MTX infusion, 0.39 +/- 0.11 g/m2 (P < 0.01). A significant increase in proteinuria (> 0.2 g/m2 post- vs pretreatment) was detectable in 54% of the patients. In the period 1991-1992 we modified the hydration-alkalisation schedule to include i.v. prehydration for 18-24 h at 3 l/m2/day with a 0.45% NaCl-5% glucose solution along with sodium bicarbonate and posthydration for 72 h with the same solution. On this protocol the mean values determined for the urinary protein content were all in the normal range (pretreatment, 0.03 g/m2/day; day 1, 0.05 g/m2/day; and day 2, 0.08 g/m2/day). These findings were significantly different from the previous results (P < 0.05).
 ...
PMID:Proteinuria due to suboptimal hydration with high-dose methotrexate therapy. 826 9

32 cases of postoperative osteogenic sarcoma treated by chemotherapy combined with Chinese medicinal herbs were compared with 26 similar cases as control group. The drugs used in chemotherapy consisted of two regimens, DDP and high-dose MTX plus VCR. The results showed that the side effects of chemotherapy in control group were consistent with literatures; while the group treated with Chinese medicinal herbs suffered less toxic effects, the difference between two groups was statistically significant. The medicinal herbs used to reduce the side effects induced by DDP was Pinellia ternata, Amomum cardamomum, Bambusa textilis, Citrus reticulata etc.; while the herbs used to alleviate the adverse effects of high-dose MTX plus VCR was Gypsum, Anemarrhena asphodeloides, Rehmannia glutinosa, Ophiopogon japonicus, Scrophularia ningpoensis, etc.
 ...
PMID:[32 cases of postoperative osteogenic sarcoma treated by chemotherapy combined with Chinese medicinal herbs]. 833 32

The relationship between the serum concentration of methotrexate and the prognosis has been studied in 108 patients with osteosarcoma of the extremities treated from September 1986 to December 1989 at the Chemotherapy Department of Rizzoli Hospital. The protocol of neoadjuvant chemotherapy included high doses of methotrexate (HDMTX) adriamycin, cisplatinum, ifosfamide and VP-16. After a median follow-up of 40.4 months (range 24-62), 84 (77.7%) of the patients studied remained continuously disease-free (CDF) and 24 relapsed. Significantly higher mean serum MTX concentrations were observed in the patients who remained CDF (669.5 mumol/l) than in the patients who relapsed (571.9 mumol/l) (p < .004). The breaking point of prognostic significance for the serum MTX levels seems to be 700 mumol/l. In fact, according to the mean MTX concentrations, the patients with less than 700 mumol/l showed a significantly lower disease-free survival than the patients with higher mean MTX concentrations (68.12% vs 94.87% p < .0013). The distribution of prognostic variables between the two groups was the same in terms of site and histological type of tumor and alkaline phosphatase serum levels at diagnosis. In the group which had more than 700 mumol/l MTX, a higher percentage of good histological response after primary chemotherapy was observed. This is probably independent from the MTX because no significant preoperative MTX serum levels between good and partially responding patients were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Serum methotrexate (MTX) concentrations and prognosis in patients with osteosarcoma of the extremities treated with a multidrug neoadjuvant regimen. 851 97

To improve the final treatment results in children with osteosarcoma, we applied after French DD-11 protocol HD MTX increasing with the younger age of patients, modified next on the basis of maximal serum drug concentrations (Cmax) as feed-back dosing. Toxic side effects were analysed according to WHO grading correlated with MTX elimination. We administered 39 HD MTX courses in 13 patients with osteosarcoma: aged 7-20 yrs (median 12 yrs). We performed 301 measurements of MTX concentration using the method of fluorescence polarisation. Therapeutic Cmax of 1000 microM/L and higher were obtained in 20 courses, the mean of lower values was 770 microM/L. We modified the next MTX doses in 23.7% of courses. Drug elimination was good in the majority of cases: in 34 of 39 courses at 24 hrs, in 36 of 39 at 48 hrs. Nevertheless, III and IV degree toxic side-effects accompanied about half of the courses and could not be predicted by MTX serum level measurements. HD MTX therapy with monitoring MTX serum levels proved feasible with acceptable toxicity. Therapeutic MTX levels were obtained in about 60% of cycles in patients with a favourable course of the disease in comparison with 25% in patients with an unfavorable course but the beneficial effect of age-tailored MTX and feed-back dosing on the treatment results will be possible to assess in the next 3 years.
 ...
PMID:[Preliminary evaluation of individualized use of large doses of methotrexate for treatment of osteosarcoma in children and adolescents]. 867 59


<< Previous 1 2 3 4 5 6 7 8 9 Next >>