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)

The primary site of metastasis of osteosarcoma is the lung. In the past, even if the primary lesion was completely removed by radical surgery, more than 90% of patients of died pulmonary metastasis with in one to two years. Control of osteosarcoma therefore depends upon the prevention and treatment of its pulmonary metastasis. The introduction of chemotherapy consisting mainly of Adriamycin and high-dose methotrexate with Leucovorin rescue, dramatically improved the prognosis of osteosarcoma. In the past where systemic chemotherapy was not available, the five-year survival rate was around 19%. The majority of patients developed bilateral pulmonary metastasis within one year after onset, and died. These patients exhibited numerous micro-metastases as well. In patients receiving surgical adjuvant chemotherapy with current combination of chemotherapeutic agents (ADM, HD-MTX, VCR, CPM, CDDP), the incidence of pulmonary metastasis was low, and the five-year survival rate increased to 65%. In patients who receive chemotherapy, pulmonary metastasis may be either delayed, a single metastasis appearing after the termination of treatment, or early and multiple, appearing resistant to treatment. Surgery is indicated in the former situation while some therapeutic system must be devised for the latter. Recently, preoperative chemotherapy for limb-saving is given to patients with osteosarcoma of the extremities (NSH-3, 4, 5). The adjuvant of chemotherapy proved to be of great significance for improving the survival rate of osteosarcoma and for achieving limb salvage.
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PMID:[Surgery and adjuvant chemotherapy of osteosarcoma]. 346 May 27

The patient was a 26-year-old male. He was admitted to our hospital with a chief complaint of hemoptysis, cough and left scrotal mass on May 9,1984. Chest X-ray film, LAG and CT revealed multiple lung, lymph node and cerebral metastases. Based on a diagnosis of testicular neoplasm, orchiectomy was performed on May 14,1984. PVB chemotherapy (Cis-diamminedichloro-platinum, Vinblastine and Pepleomycin) was administered. Because he got worse, however, he was treated with another combination chemotherapy, consisting of Methotrexate (MTX, 100 mg/m2 intravenous push (i.v.), 200 mg/m2 12-h infusion, day 1. The dose of MTX was increased with each course. Maximum dose of MTX was 900 mg/m2/day), Vincristine (1.0 mg/m2 i.v. day 1.) Actinomycin D (10 micrograms/kg i.v. days 3.4.5), Cyclophosphamide (600 mg/m2 i.v. day 3.), Adriamycin (30 mg/m2 i.v. day 8.) and Melphalan (6 mg/m2 p.o. day 8.). After 6 courses of this regimen, distant metastases disappeared or were reduced to under one tenth, and complete remission was obtained without severe side effects. The patient was in good health on March 30, 1985.
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PMID:[Case report of choriocarcinoma of testicular origin indicating marked efficacy of a combination chemotherapy of methotrexate, vincristine, actinomycin D, cyclophosphamide, adriamycin and melphalan]. 375 9

The remarkable improvement has been recently made in the treatment of choriocarcinoma, about 80% of survival rate has been achieved. This improvement was acquired according to appearance and betterment on administration method of MTX and ACTG, surgical treatment for pulmonary and cerebral metastases and irradiation for cerebral metastases. Recent died cases were analysed and divided into two groups; one group consisted of recurrent cases and the other consisted of those who, at first showed good response to therapy resulted in drop of hCG value and reduction of tumor, however, then showed gradual reincrease of hCG and expired at latt. Therefore for achieving the 0% of mortality rate, it is a important subject to exterminate the death from recurrence and clarify more aggressive treatment method at the time when reduction of the tumor is obtained.
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PMID:[Multidisciplinary treatment of choriocarcinoma]. 384 May 42

High-dose methotrexate with citrovorum factor "rescue" (MTX-CF) produced an apparent complete response of the primary tumor in three patients with osteosarcoma. The response was sustained with MTX-CF, intra-arterial cis-diamminedichloroplatinum II (CDP) and Adriamycin (doxorubicin) for 18 months. Treatment was then electively discontinued. Local recurrence occurred in two patients, 6 and 4 months later, respectively. MTX-CF was reinstated and a complete response was again achieved in one patient. This has been maintained for 15+ months with MTX-CF and intra-arterial CDP administered for 13 of the 15+ months. Reinduction with MTX-CF failed in the second relapsed patient but an apparent remission was again achieved with radiation and intra-arterial CDP. This has been maintained with intravenous CDP, cyclophosphamide and phenylalanine mustard for 14+ months. A complete response in the primary tumor was still present in the nonrelapsed patient, 42 months from diagnosis. All patients have remained free of pulmonary metastases, 40+ to 42+ months from diagnosis.
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PMID:Control of primary osteosarcoma with chemotherapy. 387 85

Over a 10 year period, between 1974-1984, 257 adult cases of tissue sarcoma have been evaluated in the Department of Medical Oncology, Christie Hospital, Manchester. At registration locally advanced or metastatic diseases was present in 162 (63%). The male/female ratio was 1.5:1 and median age 54 years (range 14-85). The commonest sites were lower limb (33%), visceral (21%), trunk (13%), retroperitoneum (12%) and upper limb (10%). Leiomyosarcoma (27%), liposarcoma (14%) malignant fibrous histiocytoma (10%) and neuro plus fibrosarcomas (15%) were the most frequent histological subtypes. A high proportion of uterine sarcomas (17%) is a point of distinction from many other series. Histological grade was specified in 72% of cases and the distribution (Grade I--27%; II--6%; III--67%) reflected a referral bias towards advanced disease. Local resection of the primary tumour was performed in 76% of cases. In many instances this only amounted to 'shelling out' and true compartmental excisions were rare. Amputation was performed in 31% of patients with limb sarcomas. Ninety-eight patients (38%) had experienced one or more local recurrences prior to referral and the overall local recurrence rate was 56%. Suitable patients (78%) received chemotherapy, 50% entering multicentre trials in collaboration with the EORTC. The commonest regime used in patients with advanced disease was CYVADIC which produced an overall response rate of 37%. Ifosfamide, used as a single agent in 16 patients, induced 3CR and 5PR for an overall response rate of 50%. When used in combination with MTX and VADIC, there was no difference in response rate, but numbers in these pilot studies were small. Seventeen high risk patients received adjuvant chemotherapy with VAC, but the results (11 relapses) were disappointing. An EORTC trial, comparing adjuvant CYVADIC chemotherapy with control has accrued 307 patients, 49 of these from the Christie Hospital. Preliminary results within this centre - 13/25 relapses in the control arm, 5/23 in the chemotherapy arm-suggest an advantage for chemotherapy but the data are statistically not significant. Post-operative radical radiotherapy after resection of the primary tumour or local recurrence was performed in 51 patients, with local control in 65% of cases, although metastases developed in 41%. At the time of analysis (1st April 1984) 98 (38%) were alive, of whom 72 showed no evidence of disease and 52 had never relapsed. Malignant disease was the cause of death in 92%. Overall survival was not influenced by sex, but patients less than 40 years of age fared significantly better (P less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Combined modality management of local and disseminated adult soft tissue sarcomas: a review of 257 cases seen over 10 years at the Christie Hospital & Holt Radium Institute, Manchester. 397 Aug 10

The methotrexate concentrations in the lungs or cutaneous metastases of patients with osteogenic or soft-tissue sarcoma were determined at different times after a high-dose methotrexate therapy. The levels in the metastases were 0.964 to 2.96 X 10(-7) molar six to nine days after the end of MTX infusion. They were thus 7.8 to 28 times higher than the corresponding serum levels. At the same time, an appreciable rise of dihydrofolate reductase activity was observed in the metastases. After chromatographic separation over Sephadex G15, MTX polyglutamates could be demonstrated in all tumor samples investigated so far; these amounted up to 68.3% of the total MTX. Taking into account the slower efflux of MTX polyglutamates compared to unchanged MTX, a new hypothesis for the principle of action of high-dose methotrexate therapy is discussed: the very high MTX doses lead to such high intracellular MTX concentrations even in transport-resistant tumor cells that at least part of the MTX is converted into MTX polyglutamates. Unchanged MTX flows relatively rapidly out of the cells, whereas the MTX polyglutamates only break down very slowly and thus can be cytostatically effective over a long period of time.
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PMID:Methotrexate and methotrexate polyglutamates in human sarcoma metastases after high-dose methotrexate therapy. 619 16

Human breast cancer cells in tissue culture can be growth inhibited by tamoxifen, an inhibition that can be reversed by estrogen. The question of whether tamoxifen inhibition of breast cancer followed by estradiol reversal would increase the efficacy of chemotherapy was asked. One hundred ten patients were prospectively randomized to chemotherapy consisting of cytoxan (750 mg/m2) and Adriamycin (30 mg/m2) on day 1 plus 5-fluorouracil (5-FU) (500 mg/m2) and methotrexate (MTX, 40 mg/m2) on day 8 versus the same chemotherapy plus tamoxifen (20 mg/m2) on days 2-6 and premarin (0.625 mg every 12 hours for three days) on day 7. Chemotherapy was given in 21-day cycles. The first 55 patients were randomized to a regimen in which 5-FU preceded MTX by 24 hours; thereafter, all patients received MTX followed in one hour by 5-FU. No difference in any response parameter was seen between these two 5-FU/MTX schedules. A limited number of patients with inflammatory breast cancer had a significantly higher response rate (93% versus 61%; p = 0.03) than patients with recurrent metastatic disease. Time to progression (13 versus 17 months) and survival (17 versus 23 months) of responders significantly favored the treatment arm including tamoxifen and premarin. Whereas an additive effect of hormones plus chemotherapy cannot be entirely excluded as the explanation for the improved results with the addition of tamoxifen for four days plus one day of premarin, results suggest that further efforts to increase the efficacy of chemotherapy by perturbing tumor growth rates may be worthwhile.
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PMID:A randomized attempt to increase the efficacy of cytotoxic chemotherapy in metastatic breast cancer by hormonal synchronization. 632 86

9 patients with osteosarcoma were treated with a total of 122 infusions of high-dose methotrexate (MTX; 140-350 mg/kg) followed by leucovorin rescue. Plasma kinetics of MTX and 7-hydroxymethotrexate (7-OH-MTX) has been routinely monitored. Due to inadequate hydration and alkalinization, 1 of the 122 high-dose MTX infusions was followed by delayed disappearance of MTX and 7-OH-MTX from plasma with subsequent development of severe mucositis. Serious hepatotoxicity repeatedly developed in another patient with inconspicuous MTX kinetics. The benefit of monotherapy with high-dose MTX for adjuvant treatment of osteosarcoma remains questionable, since 6 of 8 patients with primary osteosarcoma developed pulmonary metastases within 4-12 months (median 5 months), 2 have been disease-free and alive for 25 and 53 months.
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PMID:High-dose methotrexate for osteosarcoma: toxicity and clinical results. 660 Aug 27

Twenty year's (1959-1979) experience in the treatment of osteosarcoma at the Bone Tumor Center of the Istituto Ortopedico Rizzoli is presented. During this period 433 cases were recorded, but only 266 were considered. All the patients underwent surgery but after 1970 whole-lung irradiation (1971), immunotherapy (1971), and chemotherapy (1972 onward) were added as adjuvant therapies on a nonrandomized basis. In the group treated with surgery alone the prognosis was very poor: 10% survived nine years or more after the diagnosis, an average disease-free interval of 7.7 months and an average survival time of 13 months. Monolateral whole-lung irradiation had negative results and was abandoned after six cases. Adjuvant immunotherapy with irradiated autologous tumor cells gave moderately positive results in 16 patients, but only by delaying the appearance of first metastases, therefore increasing the time of survival. Adjuvant chemotherapy was performed with three different protocols: one protocol with ADM only and two protocols using VCR + MTX (at medium dose) + ADM, administered according to two different schedules. Superimposable results were obtained with these three regimens. With equal follow-up, the percentage of continuously disease-free patients treated with adjuvant chemotherapy was significantly higher than that of patients treated with surgery alone (P less than 0.001). The patients in the chemotherapy group who had relapses showed a prolonged time (mean = 12.3 months) to the onset of the first metastasis. Adjuvant chemotherapy caused virtually no morbidity and no deaths. Reference is made to the advantages of a large and homogeneous caseload deriving from a single institution to avoid preselection bias and evaluate the effectiveness of new therapeutic approaches when patient randomization has not been employed.
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PMID:The treatment of osteosarcoma of the extremities: twenty year's experience at the Istituto Ortopedico Rizzoli. 694 43

Forty-three patients, ranging in age from 7 to 30 years (median age, 17 yr), with primary osteogenic sarcoma (OS), confirmed by biopsies and with no evidence of metastatic disease at the time of diagnosis, received T-7 chemotherapy for an average of 4 months before surgery, including high-dose methotrexate (HDMTX) and citrovorum factor rescue (CFR) (median, 7 courses), and 1 course each of bleomycin, cyclophosphamide, and dactinomycin, and adriamycin. At the time of definitive surgery, the surgical specimen showed a good histologic response to chemotherapy (grade III or IV response) in 29 (67%) of 43 patients and a poor histologic response (grade I or II response) in 14 (33%) of 43 patients. Among those who responded well, no patient relapsed, as all received a complete course of preoperative and postoperative chemotherapy for more than 5 to over 28 months after the initiation of treatment (medium, 13 mo). Among those who responded poorly, 6 of 14 patients relapsed with pulmonary metastases (a thoracotomy was beneficial to 1), 4 of 6 patients are alive with disease, and 1 patient died of progressive disease. On retrospective analysis, we observed that good and poor responders did not differ in the distribution of sex, age, race, primary site of disease, or histologic subtype of OS. An elevated alkaline phosphatase level that returned to normal under preoperative chemotherapy indicated a good response. Neither the 24-, 48-, and 72-hour serum MTX levels nor the fluid intake and urinary output during 3 days that followed HDMTX with CFR correlated significantly with tumor response. Based on our studies with this form of therapy, we concluded that the response of OS to preoperative chemotherapy is of prognostic value.
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PMID:Prognostic factors in the response of primary osteogenic sarcoma to preoperative chemotherapy (high-dose methotrexate with citrovorum factor). 697 39


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