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 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

A 44-year-old patient with histologically proven bilateral ulcerated lymph node metastases from a carcinoma of the penis was treated by sequenced combined chemotherapy and radical irradiation. Methotrexate and bleomycin were administered at weekly intervals for 5 weeks, followed by radiation with a split-course coning-down technique. The patient remains well and clinically disease-free 63 months after commencing therapy.
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PMID:The treatment of bilateral ulcerated lymph node metastases from carcinoma of the penis. A case report. 620 40

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

The randomized Radiation Therapy Oncology Group (RTOG) Methotrexate trial in advanced squamous cancers of the head and neck has reported no control or survival benefits when the chemotherapy adjuvant was administered to patients just prior to definitive irradiation. The required data collection and outcome reporting among 146 patients bearing oral cavity primaries and 354 patients with oropharyngeal cancers has allowed a multi-variate approach seeking answers to many unresolved questions. As anticipated, the ability to control these squamous cancers is largely a function of size (T & N stage) with a superior clearance among T3-4 primaries of the oropharynx (66%) contrasted to identically staged oral cavity tumors (48%). Adjusted median survival is more than doubled to 26.6 months or 19.8 months among oral cavity and oropharynx patients respectively, when compared to the 8 month median survival when neither primary nor cervical nodes are controlled. Lymph node deposits also impact upon survival, especially among oropharynx patients where the 17.6 month adjusted median survival among N0 patients declines to 11.0 months when the primaries are associated with N3 nodes. Surprisingly, the ability to control nodel deposits of all sizes (N1, N2, or N3) is superior among oropharynx patients when compared with identical oral cavity metastases (e.g. 71.4% adjusted clearance in N3 oropharyngeal deposits versus 46.1% in N3 nodes secondary to oral cavity primaries). Adjustments for maldistribution of advanced N-stages in association with T-4 primary stage eliminated an apparent T-stage effect upon nodal clearance within both anatomic regions. Finally, the association of T and N-stage upon distant metastases was investigated, with the surprising conclusion that neither initial T nor N-stage exerts any apparent influence on the observed 10-12% occurrence. The interrelationship of these various prognostic variables is explored using the Cox and logistic models.
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PMID:Tumor regression and other prognosticators in advanced head and neck cancers: a sequel to the RTOG methotrexate study. 634 89

Methotrexate osteopathy is an uncommon complication of long-term oral maintenance therapy for childhood neoplasms, most commonly acute lymphocytic leukemia. It is characterized by severe lower extremity pain and by osteoporosis particularly involving the lower extremities and thick dense provisional zones of calcification and growth arrest lines resembling scurvy. Fractures may occur. The appearance must be distinguished from recurrent or metastatic disease.
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PMID:Methotrexate osteopathy. 642 36

About 80 per cent of patients with breast cancer ultimately die of metastatic disease in the following twenty years. Distant metastases are more important as cause of death than loco-regional relapses, it is why adjuvant chemotherapy is necessary, especially in young patients and in those with extensive disease. Initial chemotherapy preceding any locoregional treatment is justified on the basis that both surgery and anesthesia lead to immuno-depression. Further, the value of initial chemotherapy has been demonstrated in many experimental and clinical trials of Nissen-Meyer, Bonadonna and Cooper. We have treated 145 patients, including 67 with inflammatory breast cancer (IBC), with 4 to 6 weeks of Velbe, Thiotepa, Methotrexate Fluorouracil and Prednisone with Adriblastine added for those patients with IBC or T greater than 7 cm, or N2 N3. Because of tumor regression of more than 50 per cent observed in 80 per cent of the patients, the majority (123 patients) then received radiotherapy alone (cobalt + iridium) and are in a complete remission in all these cases after curietherapy. Maintenance treatment with the same drugs was prescribed for 6 to 18 months depending on the initial staging. Tumor regression appears to be an important prognostic factor. Median follow-up is only 17 months, the longest one being 42 months. The overall survival at 2 years for IBC, is 90 per cent with a disease-free survival of 80 per cent. Cosmetic results are excellent. While these results are encouraging, longer follow-up is needed to confirm this improvement.
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PMID:[Breast cancer: chemotherapy preceding locoregional treatment with extension of the indications for conservative treatment]. 643 62

Primary chemotherapy in carcinoma of the breast is justified by the high risk of distant metastases, immunodepression related to surgery and the experimental studies and clinical trials of Nissen-Meyer in 1967, and Fisher in 1968. Chemotherapy was associated with loco-regional Patey-type surgery (20 patients) or radiotherapy with cobalt and irridium (43 patients) in 63 cases of breast cancer, 33 of which were T4 or in exarcerbation. Initial chemotherapy comprised 3 to 6 infusions of Velbe, Thiotepa, Methotrexate, 5-Fluoro-uracil, prednisone plus adriamycine in the severe forms. Over 50 p. 100 tumour regression was observed in 80 p. 100 of patients without major toxicity reactions. In all cases of radiotherapy alone, the tumour disappeared completely in the two months after the end of radiotherapy. Only one of the 63 patients relapsed at the 8th month and she died. The follow-up period now ranges from 3 to 29 months (average 12 months). These results are encouraging but only a larger series will allow definite conclusions to be drawn.
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PMID:[Primary chemotherapy in breast cancer. Preliminary results]. 647 66

The metastatic involvement of leptomeninges is an uncommon complication of systemic cancer, but there are evidences that its incidence is increasing, particularly for breast cancer. The two commonest primary sites are the breast and the lung and adenocarcinoma is the most frequent histologic type of carcinoma to metastasize to the leptomeninges. Clinical diagnosis is suggested by the simultaneous occurrence of symptoms and signs in more than one areas of CNS. Examination of cerebrospinal fluid is the most helpful diagnostic procedure. A combination of radiotherapy and intrathecal or intraventricular administration of Methotrexate seems to be the most successful treatment.
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PMID:[Leptomeningeal carcinomatous metastases]. 654 14

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

The Noble rat prostatic adenocarcinoma, Nb-Pr-A.I.-II, an androgen-insensitive tumor, is the subject of this experiment. Dose responses were carried out with treatment of these tumors with three doses of adriamycin and two doses of methotrexate. Adriamycin treatment resulted in decreased tumor volume and decreased number of metastases in the higher dosage. Methotrexate also decreased metastasis and tumor volume. No animal treated with either of these agents in this protocol had the tumor undergo complete tumor regression, a criteria used in evaluation of chemotherapies with this animal model.
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PMID:The Nb rat prostatic adenocarcinoma's dose response to methotrexate and adriamycin. 663 10


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