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

Sixty postmenopausal patients with microscopically confirmed, progressive mammary carcinoma and local recurrence alone or in combination with distant metastases or with distant metastases only, not previously treated with cytostatics, were given tamoxifen (Nolvadex), 10 mg 3 times daily. The response rate in 37 evaluable patients was 48 per cent, with a median duration of the response of 26+ weeks. The effectiveness of the drug increased significantly with an increasing interval between primary treatment and the appearance of the first recurrence. No serious side effects occurred.
 ...
PMID:Tamoxifen treatment of advanced breast carcinoma. 9 2

The results obtained in 26 patients suffering from metastatic cancer of the breast no longer sensitive to hormone treatment are reported. The patients were treated with ciclophosphamide (CTX) (500 mg i.v.) once a week and triethylenethiophosphamide (20-30 mg i.m.) (TSPA) every 4 weeks associated with cyclophosphamide as follows: CTX--CTX--CTX--CTX+TSPA. 9 objective regressions (34.6%) were observed. Those with objective regression lived 28 months on average (SD 23.45) and those without lived on average 11.41 months (SD 9.89). The difference is statistically significant. Side effects of various types were observed in 7 patients (27%).
 ...
PMID:[Treatment of advanced breast cancer with alkylating agents]. 40 84

To gauge the impact of intensified therapy on the survival of infants (younger than 1 year, n = 129) and children (greater than or equal to 1 year of age, n = 275) with neuroblastoma, we analyzed the results of eight successive clinical trials comparing various combinations of antineoplastic drugs, surgery, and radiotherapy. Changes in treatment did not affect the survival of children with involved noncontiguous lymph nodes or distant metastatic disease until the combination of cisplatin and teniposide (CDDP/VM26) was added to a basic regimen of cyclophosphamide and doxorubicin (CTX/DOX). The resulting 4-year survival was 28% +/- 5% (SE) compared with 7% +/- 2% for previous treatments (P less than .001 by the log-rank test). The 4-year survival of infants with metastatic disease was improved by administering CTX/DOX to all patients, reserving CDDP/VM26 for those whose disease was resistant to the former combination: 82% +/- 6% versus 45% +/- 8% in earlier studies; P less than .001. In the subset of infants whose tumors had disseminated to bone or bone marrow at diagnosis, this therapeutic approach increased the probability of long-term survival from 48% +/- 10% to 85% +/- 9% (P = .01). The small group of children over 1 year of age with localized unresectable tumors also fared significantly better with the switch to CTX/DOX chemotherapy (4-year survival, 93% +/- 7% v 42% +/- 13%; P = .02). Multivariate analysis indicated that young age, limited-disease stage, nonadrenal primary site, and intensified treatment were independent predictors of a more favorable outcome. We conclude that substantial advances in the treatment of neuroblastoma have occurred over the past 25 years at this institution. The current overall 4-year survival probability of 57% +/- 4% compares favorably with estimates for most other common solid tumors of childhood.
 ...
PMID:Impact of intensified therapy on clinical outcome in infants and children with neuroblastoma: the St Jude Children's Research Hospital experience, 1962 to 1988. 183 94

Between 1968 and 1980, 107 consecutive patients with Ewing's sarcoma of bone were entered on three sequential combined modality treatment protocols (S2, S3, S4) at the National Cancer Institute (NCI). Protocol treatment involved 4 cycles of two drug [cyclophosphamide (CTX) and vincristine (VCR)] or three drug [CTX and VCR with either actinomycin-D (ACT-D) or doxorubicin (ADR)] regimens and local irradiation (50 Gy) to the involved bone. Eighty patients presented with localized disease and 27 patients had metastatic disease at presentation, including 11 patients with multiple metastatic sites. With a median potential follow-up of greater than 15 yrs (range 8-20 yrs), 28 pts (27%) remain alive. Disease-free (DFS) and overall survival (OS) decreased most rapidly during the initial 5 yrs of follow-up with 5-yr DFS of 29% and 5-yr OS of 39%. Only two patients with metastases at presentation are long term (greater than 5 yr) survivors. For localized disease patients, the 2, 5, 10, and 15 yr DFS and OS are 52%, 37%, 35%, and 33% DFS and 68%, 51%, 39%, and 34% OS, respectively. Eleven patients relapsed locally as the first site of failure. Using the Cox proportional hazards model, four significant variables for both DFS and OS were recognized, including metastatic disease at presentation, age greater than 25 yrs, high LDH in localized disease patients, and central primary tumor in localized disease patients in decreasing order of significance. We conclude that a majority of these patients with Ewing's sarcoma of bone relapsed within 5 yrs of presentation although late relapse (5-15 yrs) did occur. Local failure occurred in 20% of patients using these combined modality treatments but had no impact on overall survival.
 ...
PMID:Long-term follow-up of Ewing's sarcoma of bone treated with combined modality therapy. 199 54

Eighty-seven postmenopausal patients have been randomised to receive either radiotherapy or Nolvadex (tamoxifen) as first line treatment for locally advanced (stage III) breast cancer. After a median follow-up of two years no significant differences have been found in the rate of progression of local disease, the time to development of overt metastases or survival.
 ...
PMID:The early results from a randomised study of radiotherapy versus Nolvadex (tamoxifen) as initial treatment for stage III breast cancer. 337 76

The Christie Hospital Tamoxifen Trial was a randomised trial to assess the efficacy of tamoxifen (Nolvadex) as an adjunct to surgical treatment for operable breast carcinoma. From 1 November 1976 to 1 June 1982 1005 patients were registered, of whom 961 are evaluable. Following surgery, premenopausal women were randomly allocated to either tamoxifen (TAM) 20 mg/day for 1 yr or to have an irradiation menopause. Postmenopausal women had TAM 20 mg/day for 1 yr or no further treatment (controls). The analysis at 7 yr shows that there is no statistically significant difference in the overall survival for premenopausal women between those given TAM and those given ovarian irradiation. Similarly for the postmenopausal women there was no significant difference in overall survival between the TAM and control groups. However, if the series of 961 patients is analysed as a whole and allowance is made for node status then the TAM-treated patients show a significant survival benefit (P = 0.05). There was also a statistically significant delay in first relapse for the TAM-treated patients (P = 0.04); with a particularly marked reduction in distant metastases in postmenopausal patients (P = 0.06). TAM was extremely well tolerated, with very few side-effects.
 ...
PMID:The Christie Hospital tamoxifen (Nolvadex) adjuvant trial for operable breast carcinoma--7-yr results. 389 66

The hormone-dependence of malignant melanoma is brought to mind by some epidemiological facts (rarely found in children, more frequently in females, higher frequency in case of prolonged use of oral contraceptives from an early age). On the other hand, estrogen receptors can be found in about 30 p. 100 of malignant melanomas. Starting from this hypothesis of a sub-population of hormone-dependent malignant melanomas, it seemed of interest to us to study the efficiency of an anti-estrogen, namely Tamoxifen (Nolvadex) in the management of metastatic malignant melanoma. It was used at a 40 mg daily dose-regimen on four patients (three post-menopausal females, one male) with multiple estrogen positive cutaneous metastases. In post-menopausal women, two cases of total regression were observed, associated with a distinct increase in progesterone receptors while under treatment and with a return to the initial stage when the treatment was stopped. This phenomenon can be explained by a double self-contradictory effect of the drug, already well known in other hormone-dependent cancers such as those of the breast or the endometrium, namely an anti-estrogen result on the tumoral growth and an estrogen result as attested by the synthesis of progesterone receptors. Certain malignant melanomas therefore behave as endocrine-dependent tumours and may so answer an anti-hormone treatment through a competitive fixation on estrogen-receptors. Our clinical results are in agreement with such a theory since Tamoxifen is at best effective on cutaneous metastases of post-menopausal women. The overall efficiency on all metastases is of the order of 10.6 p 100 (complete or partial regression).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Role of an anti-estrogen, tamoxifen, in the treatment of metastatic malignant melanoma]. 402 32

Resistance of mouse M5076 (M5) ovarian reticular cell sarcoma to cyclophosphamide (CTX) was obtained in vivo by repeated drug treatment followed by transplantation of the regrowing tumor. After 16 passages, we obtained an M5 subline resistant to CTX (M5-CTX-16R). Median survival times were approximately 29 and 39 days for M5 and M5-CTX-16R, respectively. Survival of M5-bearing mice given a single i.p. dose of 200 or 300 mg/kg was 160 and 168% of controls, respectively, whereas in M5-CTX-16R it ws 103 and 123%, respectively. The resistance was not reversible after 14 additional passages with no further CTX treatment. M5 and M5-CTX-16R appear similar in histological features, pattern of metastasis formation, and DNA content, as assessed by flow cytometry (hypotetraploid). Metastases of M5-CTX-16R were also resistant to CTX. Flow cytometry studies 12 and 24 hr after CTX treatment revealed a block in S and G2-M phases in both tumors. After 48 hr and at subsequent times, no cytokinetic pertubation was evident in M5-CTX-16R, whereas in M5 marked accumulation of cells in G2-M was observed at 48, 72, 96, and 120 hr. Cross-resistance was found between CTX, L-phenylalanine mustard, chlorambucil, and hexamethylmelamine. M5-CTX-16R was sensitive, but less so than M5, to cis-platinum, 1,3-bis(2-chloroethyl)-1-nitrosourea, and imidazole-4-carboxamide,5-(3,3-dimethyl-1-triazene). Adriamycin was equally active on M5 and M5-CTX-16R, while 4'-demethylepipodophyllotoxin-9-(4,6-O-ethylidine-beta-D-glucopyranoside) was inactive. This model appears to be suitable for studies on the mechanism of resistance to CTX and alkylating agents and for screening new, non-cross-resistant drugs.
 ...
PMID:Ovarian reticular cell sarcoma of the mouse (M5076) made resistant to cyclophosphamide. 635 29

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.
 ...
PMID:Effect of cyclophosphamide or x-rays on spontaneously occurring metastases from tumors transplanted into the tails of mice. 721 47

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.
 ...
PMID:Phase II trial of high-dose epirubicin and cyclophosphamide in advanced breast cancer. 799 14


1 2 3 4 5 Next >>