Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since January 1976 high-dose methotrexate (HDMTX) therapy has been used in the management of patients with osteogenic sarcoma at the Orthopaedic Department, University of Vienna. 7500 mg MTX/sqm body surface is administrated in a four-hour infusion with citrovorum factor rescue. This therapy is combined with dactinomycin, adriamycin, bleomycin, cyclophosphamide and vincristine in a multi-drug chemotherapeutic program as a prophylactic regimen after surgical treatment of the primary tumour, as well as in the management of metastases. So far, 12 patients have received a total of 46 infusions with HDMTX at montly intervals (6 patients already had widespread metastases). The use of several precautions such as adequate hydration 3 l/sqm body surface fluid), systematic alkalinization of the urine and regular control of the serum MTX level renders HDMTX therapy less hazardous. Five out of the 46 infusions were followed by mild toxic reactions consisting of mouth ulceration, fever and/or bone marrow depression. One out of the 6 patients with metastases and 5 out of the 6 patients receiving HDMTX as a prophylactic measure are without evidence of disease at present. In view of the short observation period, this report is limited to clinical observations only.
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PMID:[Clinical observations on the use of high-dose methotrexate treatment in osteogenic sarcoma (author's transl)]. 7 Aug 89

Vincristine-high-dose methotrexate-citrovorum factor (VCR-MTX-CF) was administered preoperatively at weekly intervals to eight patients, four with primary tumors and four with pulmonary metastases. These patients had not received prior VCR-MTX-CF treatment. A similar treatment program was administered to five patients with pulmonary metastases who had received prior VCR-MTX-CF. Among the eight patients who had not received prior VCR-MTX-CF, complete responses were obtained in three with primary tumors (this was followed by surgical excision) and two with pulmonary metastases. Partial responses occurred in two additional patients. Partial responses were also obtained in two patients who had received VCR-MTX-CF. Chemotherapy and surgery in one patient with an extremity lesion resulted in preservation of the limb and useful function. The major toxicity was anorexia and weight loss. Other side effects included stomatitis, myelosuppression, hepatitis and transient renal impairment. The weekly program was highly effective when compared to responses obtained with the tri-weekly schedule utilized in previous studies.
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PMID:Weekly high-dose methotrexate-citrovorum factor in osteogenic sarcoma: pre-surgical treatment of primary tumor and of overt pulmonary metastases. 29 28

From January 1984 to June 1990, we observed 42 patients with meningeal carcinomatosis, 20 men and 22 women, aged 21 to 80 years (median age, 53 years). The two most common primary malignancies were lung cancer (50%) and breast cancer (31%). Sixty-four per cent was adenocarcinoma. On the first lumbar puncture, 86% had malignant cells in the cerebrospinal fluid. The findings of brain computed tomography were hydrocephalus (62%), contrast enhancement in the cerebral sulci or basal cisterns (31%), concomitant parenchymal metastases (15%) and normal scan (18%). In five out of seven cases, myelography showed irregular filling defects over the spinal cord or cauda equina. Treatment results were evaluated in 24 patients. Eight received radiation therapy (RT) alone, and 16 had combined therapy with RT plus intrathecal methotrexate (IT MTX). Of the patients who received RT alone, only one patient with lung carcinoma was stabilized clinically. Of the cases receiving combined therapy, seven improved clinically. Six of these were patients with breast carcinoma who received IT MTX via Ommaya reservoir. The latter had a median survival of 23 weeks. The follow-up period of the entire group of patients ranged from one day to 50 weeks. The median survival was four weeks. Based on this study, combined therapy with RT and IT MTX is indicated for breast carcinoma with meningeal carcinomatosis, but the therapeutic effects are uncertain for lung carcinoma and other malignancies.
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PMID:Meningeal carcinomatosis from solid tumors: clinical analysis of 42 cases. 135 92

The study comprised 97 patients treated by the Scandinavian Sarcoma Group for high-grade, extremity-localized osteosarcoma. Chemotherapy was according to the T-10 protocol, with four courses of high-dose methotrexate (HDMTX) given preoperatively at weekly intervals. Seventeen percent of the patients obtained a good (grade III or IV) histologic response, 62% a moderate (grade II) response and 21% a poor (grade I) response. Grade II-IV responders had significantly higher serum MTX levels than grade I responders. Good responders had significantly better survival than moderate/poor responders, and had a trend towards both lower recurrence rate and longer time to recurrence. Five-year overall and relapse-free survival for all patients was 63% and 53%, respectively. Within a group of patients with similar primary tumour response, there was a trend for better survival with increasing serum MTX levels, indicating that individualization of MTX doses according to renal excretion rates may be indicated. The present results underline the importance of introducing effective chemotherapy from the start of osteosarcoma treatment, and that HDMTX alone seems to be insufficient preoperative therapy. The toxicity of HDMTX is generally mild, but we have by cerebral MRI found signal changes in white matter in 14/22 patients; changes that may represent subclinical MTX CNS toxicity. In the subsequent SSG osteosarcoma protocol, cisplatin and doxorubicin has been added to HDMTX from the start of treatment. Our data also suggest that an aggressive approach involving second-line chemotherapy and surgery is indicated for metastatic disease and that such an approach may lead to long-term survival in up to 30% of patients.
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PMID:The treatment of osteosarcoma: present trends. The Scandinavian Sarcoma Group experience. 162 72

Ninety-eight pediatric patients were treated with three separate protocols (Treatment and investigation of Osteosarcoma [TIOS] I, II, and III) and 47 developed recurrent disease (metastases and/or local recurrence). Actuarial overall disease-free survival (hereafter designated survival) was 43%. Over 90% of the patients were treated initially with preoperative intraarterial cisplatin (CDP). Postoperative chemotherapeutic regimens comprised high-dose methotrexate with leucovorin rescue (MTX-CF), Adriamycin [( ADR] doxorubicin; Adria Laboratories, Columbus, OH), and cyclophosphamide. Primary definitive treatment comprised amputation or limb salvage (TIOS I and TIOS III). Patients treated with preoperative CDP and surgery (TIOS I and III) had a 62% survival. Patients in TIOS II refused surgical extirpation; they were treated exclusively with chemotherapy and had a 23% survival. Survival in patients treated with amputation was 55% and limb salvage 58%. Prognostic factors considered significant in relation to development of pulmonary metastases comprised tumor burden (P = .04) and the percentage of tumor necrosis induced by preoperative chemotherapy (P = .01). Histopathologic subtype was marginally significant: chondroblastic was more favorable as opposed to osteoblastic (P = .05). These findings are compared with results and prognostic factors published in the literature.
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PMID:Pediatric osteosarcoma: therapeutic strategies, results, and prognostic factors derived from a 10-year experience. 223 Aug 90

From Jan. 1979 to Nov. 1987, 38 patients with invasive mole and 5 patients of choriocarcinoma were primarily treated with methotrexate and citrovorum factor (MTX-CF) rescue. Thirty-two patients had non-metastatic disease (stage I) and 11 had metastatic disease (stage IIA in 5 cases, stage IIB in 3 cases and stage IIIA in 3 cases). Complete remission was achieved in 28 (87.5%) of 32 patients with non-metastatic disease and in 9 (81.8%) of 11 patients with metastatic disease. Six patients with MTX-CF resistant tumors subsequently achieved complete remission with intravenous infusion of KSM and/or AT 1258. All patients were followed up periodically, 22 of them have been followed up for over 2 years, the longest duration of follow-up being 7 years. Seven of the 14 patients with preserved uterus became pregnant after recovery. All children grew up normally.
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PMID:[Treatment of gestational trophoblastic neoplasms with methotrexate and citrovorum factor rescue: analysis of 43 cases]. 256 Oct 92

With the combined osteosynthesis of pathological fractures in association with tumors and/or metastases in mind, E. Merck (Darmstadt, FRG) developed a bone cement containing a cytostatic agent, methotrexate-Palacos flow y (MTX-Pf). The animal-experimental study presented here investigates the tolerability of MTX-Pf in the femurs of rabbits with lateral comparison. In these investigations we used both the concentration of 0.63% MTX, as is currently used in standard clinical surgery, as well as a much higher concentration of 2.5% MTX. The histological sections were investigated using microradiographic methods and provided no indication of any significant differences between the femora with the MTX-Pf implantation and those into which standard Palacos flow y had been implanted.
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PMID:Reaction of the bone structure to methotrexate-Palacos flow y. Experimental investigations in animals. 261 23

Five different types of anticancer drugs were individually entrapped into fibrin clots using our own material, "G.T.XIII" to provide an "anticancer drug-fibrin clot" for regional cancer chemotherapy. Anticancer drugs used in the present study were ADM, MMC, MTX, 5-FU and cDDP. The release of drugs from fibrin clots was studied in vitro. Each fibrin clot was intraperitoneally administered to cancer (AH-130)-bearing rats to evaluate the oncolytic effects. The activities of anticancer drugs delivered from the clots were maintained for more than two weeks. Survival terms of cancer bearing rats were remarkably prolonged with the anticancer drug-fibrin clots. Neither recurrence of ascites nor metastases of malignant cells was observed in the rats treated with such clots. Our newly devised anticancer drug-fibrin clots showed a sustained release of oncolytic drugs and favorable antineoplastic effects. This newly devised drug delivery system suggested a clinical potential for regional cancer chemotherapy.
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PMID:[Loco-regional cancer chemotherapy with a new drug delivery system, "anticancer drug-fibrin clot"]. 278 91

Between January 1980 and October 1987, 115 evaluable patients were treated in Sheffield for persistent gestational trophoblastic disease (GTD) with a low dose methotrexate regimen (LD-MTX). Each course comprised MTX 50 mg given by i.m. injection for 4 doses on alternate days. Courses were repeated every 2 weeks and serum beta-hCG was used to monitor response. Overall, 80/115 (70%) of patients attained durable complete remissions (CR). Twenty-nine patients received the 'AVC' salvage combination of actinomycin-D 0.5 mg i.v. for 5 days, sequenced with cyclophosphamide 500 mg i.v. and vincristine 1 mg i.v., both given for 3 doses on alternate days. Sixteen (55%) patients attained a durable CR but 11 (38%) required further measures, 7 ultimately requiring hysterectomy. Two (7%) died during treatment. With 4 deaths overall (3 from metastatic GTD and 1 from infarction of the bowel), actuarial survival is 94% at over 7.5 years. A new Charing Cross prognostic scale weighted especially for hCG levels, number and sites of metastases, interval between pregnancy and start of treatment (score 0-6 each factor), was applied retrospectively to obtain a total score for each patient. Thus, 21/26 (81%) patients who scored greater than 8, required additional treatment after LD-MTX, compared with 18/89 (20%) of lower scoring patients (p less than 0.001). Because of the frequent morbidity associated with prolonged chemotherapy as well as the development of drug-resistant GTD, it is concluded that the 'high-risk' patients should receive more intensive combination chemotherapy at the outset.
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PMID:Results of low-dose methotrexate treatment of persistent gestational trophoblastic disease in Sheffield 1980-1987. 284 67

From 1971 to 1981, twenty patients with poor-prognosis metastatic gestational trophoblastic neoplasia (GTN) were treated with moderate-dose methotrexate (1 g) and folinic-acid rescue (MD-MTX-FAR) as initial therapy. Seven (35%) were cured with MD-MTX-FAR, and salvage chemotherapy was successful in an additional seven, for a total cure rate of 70%. The ultimate outcome is similar to that reported for MAC triple therapy during this era. Hematologic and mucosal toxicity were negligible and no serious complications were encountered. We now use combination chemotherapy in patients with poor-prognosis GTN as first-line treatment. However, these results suggest that there may be advantages to the incorporation of MD-MTX-FAR in combination regimens in place of low-dose methotrexate, because of reduced toxicity and potential benefits for the prophylaxis and treatment of cerebral metastases.
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PMID:Poor prognosis metastatic gestational trophoblastic disease: experience with moderate dose methotrexate plus folinic acid rescue as initial therapy. 302 4


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