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)

Cyclophosphamide and prednisolone therapy was given to 83 patients with hormone-resistant disseminated carcinoma of the prostate. In 7 cases there were objective signs of regression of metastases. Significant reduction of elevated acid phosphatase activity was recorded in 11 cases, in 2 of them to normal range. 55 patients experienced pain relief, 26 of them very good. In the majority of cases duration of the remission was shorter than 6 months, in 2 cases it lasted more than a year.
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PMID:Cyclophosphamide-prednisolone therapy in advanced prostatic carcinoma. 693 21

The Surgery Branch of the National Cancer Institute conducted two prospective trials on the effectiveness of adjuvant chemotherapy in the treatment of patients with sarcomas. Adriamycin and cyclophosphamide (Cytoxan) appeared to improve significantly the disease-free survival of 55 current protocol patients with sarcomas of soft tissue compared with historical controls (P less than 0.001). The high incidence of drug-induced cardiomyopathy associated with this regimen led us to begin a prospective randomized trial of this adjuvant chemotherapy in patients with sarcomas of soft tissue. The use of high-dose methotrexate following surgery in 50 patients with osteogenic sarcoma was associated with a small increase in disease-free survival (P = 0.028) compared with historical controls. Little if any effect was seen in patients with high-grade lesions (P = 0.11). Overall survival of patients with osteogenic sarcoma was dramatically improved (P less than 0.001), probably due to the introduction of frequent screening for pulmonary metastases and the surgical resection of these metastases as soon as they appeared.
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PMID:Treatment of soft tissue and bone sarcomas: review of studies at the National Cancer Institute. 702 92

A spontaneous metastases model in mice is being used to test the efficiency of various treatments in eliminating metastases. Solid tumors were transplanted into the tails of mice and removed by tail transection when they had grown to a 4- to 5- or 6- to 7-mm mean diameter. Subsequently, 70 to 95% of mice not given other treatment developed metastases in the lungs or in regional lymph nodes (lumbar sacral region), or in both sites. The present paper reports the effects of whole-body or partial-body treatment on these metastases. The treatments, which started at the time of surgical transection of the tail, included a range of single or fractionated doses of cyclophosphamide (CTX) or X-rays given either to the whole body or locally to the lungs only. CTX reduced the incidence of metastases in both sites although the incidence of lung metastases was reduced by smaller doses of CTX than that of the lumbar sacral metastases. Whole-body irradiation of 6 grays (600 rads) had no effect on the incidence of metastases, whereas local irradiation of the lungs with single doses of 14.5 or 20 grays reduced the number substantially, as did 95 mg or more of CTX per kg. Thus, CTX or radiation reduced the incidence of lung metastases in a system where metastases developed from cells seeded from a primary tumor rather than from a cell suspension injected into the tail vein.
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PMID:Effect of cyclophosphamide or x-rays on spontaneously occurring metastases from tumors transplanted into the tails of mice. 721 47

The effects of two selective antimetastatic agents, 1-p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK), and (+/-)-1,2-di(3,5-dioxopiperazin-1-yl)propane, have been examined in comparison with those of a cytotoxic agent, cyclophosphamide, in mice bearing Lewis carcinoma. Cyclophosphamide at the two highest dosages causes a strictly related and pronounced inhibition (to less than 10%) of the weight of the s.c. tumor, spontaneous metastases, and lung colonies formed after i.v. injection of tumor cells (artificial metastases); this behavior is consistent with a purely cytotoxic mechanism. At the three dosages used, (+/-)-1,2-di(3,5-dioxopiperazin-1-yl)propane reduces the weight of spontaneous metastases to less than 3%. A dose-dependent reduction of artificial metastasis weight is also observed. At the highest dose, artificial metastasis weight is reduced to about 5%, and s.c. tumor mass is significantly lowered to 40%. These effects are consistent with the combined occurrence of cytotoxic and selective antimetastatic action, although the latter appears to be predominant. At the three dosages used, DM-COOK markedly depresses the weight and number of spontaneous metastases to about 10%, leaving the formation of artificial metastases unaffected and causing no significant effect on primary tumor growth. The effects of these agents on the fractional incorporation of [3H]thymidine in tumor cells further indicate that only DM-COOK is devoid of cytotoxic effects for pulmonary and s.c. tumors. In hosts pretreated with DM-COOK, no reduction in the formation either of spontaneous or of artificial metastases is observed. These data indicate that DM-COOK acts directly on tumor cells and that it presumably inhibits their release from the primary tumor into the bloodstream.
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PMID:Selectivity of the antimetastatic and cytotoxic effects of 1-p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (+/-)-1,2-di(3,5-dioxopiperazin-1-yl)propane, and cyclophosphamide in mice bearing Lewis lung carcinoma. 723 46

Because of the high incidence of pulmonary and skeletal metastases after only local treatment adjuvant systemic chemotherapy is mandatory in Ewing's sarcoma. The drugs most often used thereby are Actinomycin D, Cyclophosphamid, Anthracyclines and Vincristine. In polychemotherapeutic trials two year disease-free survival rates of 80% and more have been accomplished. The rate of local tumour control after radiotherapy is enhanced by chemotherapy but untoward reactions of bone and soft tissue are also. The extent of radiation portals and time indispensable dose of radiation therefore have to be reviewed again. But in view of debilitating side effects of radio-chemotherapy surgical procedures have to be considered individually.
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PMID:[On the chemotherapy of Ewing's sarcoma (author's transl)]. 726 93

The purpose of this study was to determine whether methotrexate, vinblastine, doxorubicin, and cisplatin, each individually active in metastatic breast cancer (MBC), could, in combination, produce an overall response rate, median survival, and long-term survival sufficiently promising to merit its consideration for phase III trials in MBC and as induction therapy prior to autologous bone marrow transplant. From July 1986 through February 1990, 30 patients with stage IV, measurable breast carcinoma received M-VAC: methotrexate--30 mg/m2 days 1, 15, 22; vinblastine--3 mg/m2 days 2, 15, 22; doxorubicin--30 mg/m2 day 2; cisplatin--70 mg/m2 day 2. Cycles were repeated at 4-week intervals for up to six courses. Median age was 53 years (range 34-64 years). Prior treatment included adjuvant cyclophosphamide, methotrexate, and 5-Fluorouracil in 12 patients, radiotherapy in 13 patients, and hormonal therapy in 14 patients. Eleven patients were ER (+) at the time of initial diagnosis. Five patients had disease restricted to bone and/or nodes; the other 25 had visceral-dominant sites of metastases, with or without bone involvement, or evidence of rapid, inflammatory chest wall relapse. Twenty-nine of 30 patients were evaluable for toxicity and response; all were evaluable for survival. The major overall response rate was 83%, with a 21% complete remission rate. The chief toxicity was bone marrow suppression, with grade 4 granulocytopenia in 20 patients, grade 3 in 7 patients, and grade 3 and 4 thrombocytopenia in 5 patients. Grade 3 stomatitis occurred in 9 patients. Renal insufficiency was clinically insignificant, and neurotoxicity mild, with 7 patients sustaining grade 1 or 2 paresthesias. Median time to progression was 9 months and median survival 19 months (range, 5-84+ months) with 4 patients still alive at least 45+ months or more from the start of treatment and 2 presently free of progressive disease. Although highly toxic, M-VAC produces a response rate and survival duration in visceral-dominant MBC competitive with, if not superior to, conventional regimens such as CAF (Cytoxan, doxorubicin, 5-fluorouracil); it therefore merits further investigation in conjunction with hematopoietic growth factors and as cytoreductive therapy prior to autologous bone marrow transplantation.
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PMID:Phase II evaluation of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) in advanced, measurable breast carcinoma. 787 68

Between February 1990 and December 1991 high-dose epirubicin (Epi)(120 mg/m2) plus cyclophosphamide (CTX)(600 mg/m2) were given every 3 weeks to 52 patients with locally advanced and metastatic breast cancer. 26 patients with locally advanced disease received four courses of this regimen before and after local treatments. 26 patients had metastatic disease: they received eight courses unless progression or unacceptable toxicity occurred. Responses were seen in 37/48 (77%) evaluable patients including 14 complete responses (CR), 23 partial responses (PR), nine stable disease, two progressive disease. Among the 25 evaluable patients with locally advanced disease, 9 had a CR and 11 a > 80% decrease in tumour volume. 6 patients (24%) had a pathologically confirmed complete response. 18 patients (72%) had a tumour reduction to 0-2 cm. The 3-year disease-free survival was 60%. Of the 23 evaluable patients with metastatic disease, 5 obtained a CR and 10 a PR, yielding an overall response rate of 65%. Myelosuppression was substantial with a grade 3-4 leucopenia in 76% of the patients even if neutropenic fever occurred in only 7% of the courses. A clinical congestive heart failure occurred in 1 patient following a total Epi dose of 960 mg/m2 and a bilateral quadrantectomy and radiotherapy. We conclude that (1) high-dose Epi + CTX is a very active regimen, in particular for the patients with locally advanced breast cancer; (2) breast conservation after this regimen in some of these patients may be considered; (3) neutropenia is the dose-limiting toxicity. Currently, a phase II study using the same combination given every 2 weeks together with r-methuG-CSF is ongoing.
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PMID:Phase II trial of high-dose epirubicin and cyclophosphamide in advanced breast cancer. 799 14

DN-9693, c-AMP: phosphodiesterase inhibits platelet aggregation induced by metastasizing tumor cells and blood-borne metastases of these tumors. Effects of this drug on pulmonary metastases was studied in wKA rats, which were sc implanted with 4-dimethylaminoazobenzene (DAB) induced KDH-8 tumor cells. KDH-8 cells (10(5)) were sc inoculated on day 0 and excised on day 20. DN-9693 was ip injected at a dose of 150 micrograms twice a day for 7 days pre operatively (-7 - 0) or perioperatively (-3 - +3) or postoperatively (0 - +7). The rats were sacrificed on day 20 after surgery, and lung weight and the number of surface pulmonary nodules were measured. Both were significantly decreased in the group of perioperative and postoperative administration of DN-9693. The survival of these rats were furthermore prolonged when Cyclophosphamide (40 mg/kg) was sc injected 3 days after surgical resection. KDH-8 tumor cells (10(4)) were iv inoculated on day 0, and DN-9693 was ip injected at a dose of 150 micrograms twice a day for 7 days on day 0 approximately 7. Rats were sacrificed on day 20, and same studies as above were done. In this artificial pulmonary metastases, the decrease of the number of lung nodules was observed in WKA rat treated with DN-9693. Platelet aggregation induced by KDH-8 tumor cells was inhibited by ADP inhibitor (apyrase, CP/CPK) and thrombin inhibitor (heparin, MD-805); KDH-8 tumor cells induced platelet aggregation by two different mechanisms: ADP-mediated aggregation and thrombin-mediated aggregation. This platelet aggregation by KDH-8 tumor cells was inhibited by DN-9693 with dose-dependency. DN-9693 had no direct anti-tumor effects either in vivo or in vitro. The results indicates that this drug prevents pulmonary metastases by inhibiting platelet aggregation.
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PMID:[Effects of platelet aggregating inhibitor on pulmonary metastases of tumor cells after surgical resection]. 822 73

A model was established whereby C57BL/6 (B6) blood injected i.v. into C3H mice 7 days prior to i.v. injection of syngeneic UV-2237 tumour cells significantly increased the number of pulmonary metastases counted 21 days later as compared with levels observed in mice treated with saline, C3H or NZW blood or SRBC. This regimen of B6 allogeneic blood transfusion of C3H mice also significantly depressed splenic and pulmonary NK activity as assayed by lysis of 51Cr YAC-I in vitro and by clearance of 111In YAC-I in vivo respectively. Anti-asialo GMI treatment, which depletes NK activity in vivo, and Poly I:C treatment, which enhances NK activity in vivo, were associated with significantly increased and decreased pulmonary metastasis of UV-2237, respectively, in C3H mice. Depletion of CD4+ and CD8+ T cells had no effect. Cyclophosphamide pretreatment which, among other effects, depletes NK cells, significantly increased pulmonary metastasis of UV-2237 in C3H mice. This was corrected by adoptive transfer of normal C3H spleen cells but not spleen cells from anti-asialo GMI-treated C3H mice or B6-blood-transfused C3H mice. Furthermore, a 1:1 mixture of normal C3H spleen cells with spleen cells from B6-blood-transfused C3H mice also failed to reconstitute the cyclophosphamide-pre-treated C3H mice. We conclude that allogeneic blood transfusion augments pulmonary metastasis of the UV-2237 sarcoma in C3H mice and that the mechanism involves suppression of NK activity.
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PMID:Allogeneic blood transfusion reduces murine pulmonary natural killer (NK) activity and enhances lung metastasis of a syngeneic tumour. 825 37

60 patients with metastatic breast cancer were entered in a phase II study using folinic acid, 5-fluorouracil bolus and infusion and mitoxantrone with or without cyclophosphamide. 47 had measurable visceral metastases and 13 had exclusively bone metastases. 36 had received previous adjuvant or metastatic treatment (33/36 with anthracycline-based regimens). Overall response rate in visceral metastatic patients was 57.1% [95% confidence interval (CI) 35.4-78.8%]; 45.5% and 70% in previously and non-previously treated patients, respectively; duration of response was 9 and 13 months, respectively. 10 out 13 patients with exclusive bone metastases improved for a median time of 18 months. Median survival was 22 months for the 60 patients; 18 and 31 months for previously and non-previously treated patients, respectively. Cyclophosphamide was scheduled only in the absence of nadir grade 4 neutropenia. However, this toxicity occurred in the first 7 patients. For this reason, we chose to avoid cyclophosphamide in patients over 60 years, or with a performance status of 1-2, or who had received previous chemotherapy. Overall, cyclophosphamide was stopped due to nadir grade 4 neutropenia in 17/24 patients for whom this drug was planned. When mitoxantrone, 5-fluorouracil and folinic acid were used at the doses scheduled, the addition of cyclophosphamide appeared feasible in only about 25% of the patients. Furthermore, survival was identical for patients receiving or not receiving cyclophosphamide. Therefore, cyclophosphamide does not contribute substantially to this regimen. This study confirms the value of folinic acid, 5-fluorouracil and mitoxantrone in metastatic breast cancer.
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PMID:Folinic acid, 5-fluorouracil bolus and infusion and mitoxantrone with or without cyclophosphamide in metastatic breast cancer. 826 Feb 36


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