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)

Ifosfamide (Z 4942) is an alkylating agent with the structure of a cyclophosphamide analog. Preliminary studies performed in our hospitals demonstrate the releasing effect of Ifosfamide for persistent pain caused by metastases of the prostatic cancer at various regions. Ifosfamide was given 2 grams a day intravenously with hydration and alkalization for consecutive 5 days. The regimen was performed every 3 or 4 weeks. Pain has disappeared in 7 of 10 cases within 2 or 3 courses. Pain of other 3 cases has also greatly reduced. The effective rate for the primary lesion of the prostatic carcinoma in stage C and D is 30.7%. Side effects were nausea, vomiting, hair loss and leukopenia.
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PMID:[Treatment of pain caused by metastases of reactivated prostatic cancer with ifosfamide]. 663 95

The antitumor activity and toxic effect of AMSA were studied in Lewis lung carcinoma (3LL) at various stages of growth. The total dose of drug injected IP was 15 mg/kg, which is equivalent to the LD10. Different administration schedules were tested, these being single-injection schedules (day 1, 7, or 10 after tumor implantation) and repeated low-dose-injection regimens (days 1, 4, and 7 and days 1-7 after tumor implantation). Tumor weight inhibition, retardation of growth, reduction in the number of metastases, and median survival time of treated mice over controls were analyzed as end-points to evaluate the antitumor activity of AMSA. Early deaths and changes in white blood cell count were considered as parameters of toxicity. Our findings can be summarized as follows: (1) AMSA is only minimally effective against primary 3LL tumor at all the growth stages examined and no schedule-dependency is detected; (2) a greater reduction in metastases (70%-77%) is found when the drug is administered fractionally than when it is given in a single dose (39%-60%); (3) irreversible leukopenia is induced by the single-dose schedule of AMSA administration while after repeated low doses the white blood cell counts are in the same range of those of the control groups. Therefore, because of the schedule-dependency of toxicity and reduction in metastases, fractionated administration of AMSA at this dose level would be suitable for adjuvant chemotherapy.
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PMID:Influence of scheduling on therapeutic and toxic effect of AMSA in Lewis lung carcinoma. 668 82

Radical radiation therapy (5000 rads in 20 fractions in 4 weeks) combined with iv mitomycin (10 mg/m2) and 5-FU (1000 mg/m2/24 hours for 4 days) was used to treat 13 patients with locally advanced but operable squamous cell carcinoma of the anal canal. All patients achieved local control and retained anal continence, and none developed metastases. The patients were followed from 4 to 34 months (median, 12). Severe acute gastrointestinal toxic effects were seen in three patients; the same patients had significant thrombocytopenia or leukopenia. Treatment with this combined program may allow conservative management of squamous cell carcinoma of the anal canal and should be considered as an alternative to abdominoperineal resection.
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PMID:Combined radical radiation therapy and chemotherapy for primary squamous cell carcinoma of the anal canal. 680 Jun 54

Between the years 1973-1977, 152 male patients from 28 participating Veterans Hospitals with histologically proven nonresectable cancer of the pancreas were randomized in a two-arm study. The treated group was to receive combination chemotherapy with 5-FU and CCNU, and the controls were to receive no chemotherapy. Both groups were comparable with respect to age, amount of weight loss, extent of histologically proved metastases, and operation performed. In the treatment group, drug therapy was begun between 10 and 60 days postoperatively. Intravenous 5-FU, 9 mg/kg, was administered on five consecutive days, and CCNU, 70 mg/m2, was given orally on the first day of each course. In the absence of toxicity, the course was repeated every six weeks for life; 146 drug courses were given. The incidence of toxicity was not great. One or more toxic reactions were reported for one-third of the drug courses administered, but for the most part, these were mild. The most frequent toxic reaction was vomiting in 17% of the courses, and hematologic toxicity-primarily leukopenia-in 15% of the drug courses. There was no evidence of a beneficial effect on survival from drug treatment in the group as a whole or in any subgroup analyzed. The median survival of the control group was 3.9 months, and of the drug-treated group, 3.0 months.
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PMID:Randomized study of 5-FU and CCNU in pancreatic cancer: report of the Veterans Administration Surgical Adjuvant Cancer Chemotherapy Study Group. 700 90

Vinblastine sulfate 0.10-0.15 mg/kg IV every week, was given to 37 patients with bidimensionally measurable, metastatic transitional cell carcinoma of the urothelial tract. Twenty-eight patients, the majority of whom had received extensive prior chemotherapy, had an adequate trial and five (18%; 95% confidence limits, 3-33%) achieved a partial remission (greater than 50% decrease in tumor size) of 2-5 months' duration. Responding sites included lung and nodal metastases. Toxicity, primarily leukopenia, was mild to moderate. The 18% response rate obtained in heavily pretreated cases suggests that vinblastine sulfate has some efficacy in the treatment of patients with advanced urothelial tract tumors.
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PMID:Phase II trial of vinblastine sulfate for metastatic urothelial tract tumors. 709 86

The results of treatment of 110 out-patients with breast metastases, using various repeated schemes of chemotherapy, are discussed. The results and recommendations may be integrated with the procedures of selection of schemes of breast metastasis treatment. Good tolerance, virtual absence of side--effects and complications (e. g. persistent leukopenia) were observed. Integration of the new scheme with antibiotic treatment (carminomycin and adriamycin) is suggested.
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PMID:[Use of "split" courses of combination chemotherapy in breast cancer]. 726 35

Over a period of 4 years, 241 patients with advanced cancer were treated with mecaphane alone in 11 hospitals. Effective objective responses were obtained in 100 patients (41.4%). The response was most conspicuous in chronic granulocytic leukemia, with remission in 37 of 40 patients; in Hodgkin's disease and lymphosarcoma response rates were 60% and 47.3%, respectively. Mecaphane had an analgesic action in metastatic osteolytic bone cancer, and two patients with such metastases even attained recalcification of the osteolytic destructive lesions. The common toxic manifestations of mecaphane were leukopenia (33.6%), gastrointestinal upsets (28.2%), and thrombocytopenia (12.8%). It is concluded, therefore, that mecaphane could be a good antitumor agent in clinical use. It is less expensive and can be taken orally. Further trials of this drug are recommended.
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PMID:Clinical studies on the antitumor action of mecaphane. 730 33

Combination antimicrotubule therapy with estramustine phosphate (EMP) and vinblastine has reproducible activity in metastatic hormone-refractory prostate cancer (HRPC) with an objective response rate of 31%. Although paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) by 24-hour infusion was inactive in HRPC, 0.5 to 1.0 nmol/L concentrations of paclitaxel combined with EMP exerted synergistic cytotoxicity in DU-145 androgen-independent human prostate cancer cell lines. Based on these results, we treated 24 patients with HRPC using the combination of paclitaxel 120 to 140 mg/m2 by 96-hour intravenous infusion every 3 weeks plus daily oral EMP at 600 mg/m2/d. Of seven patients with measurable soft tissue metastases, three have attained partial responses and a fourth patient is nearing partial response status. Of 16 patients with bone-only disease evaluated by change in serum prostate-specific antigen levels, 11 patients (68.8%) have had decreases of > or = 50% from pretreatment baseline. The prostate-specific antigen decrease has exceeded 80% in six of 16 (37.5%) patients. For all 23 evaluable patients, the prostate-specific antigen has decreased by > or = 50% in 15 (65.2%) and by > or = 80% in eight (34.7%). Grade 4 leukopenia occurred in one of 21 patients treated at the paclitaxel dose of 120 mg/m2/96 hr and one of three patients treated at 140 mg/m2/96 hr. The incidence of nausea (50%) and peripheral edema (37.5%) was similar to that associated with single-agent EMP. These results demonstrate that 96-hour paclitaxel plus EMP is active in HRPC and provide further evidence that the rational combination of antimicrotubule agents leads to synergistic antitumor activity in HRPC.
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PMID:Paclitaxel plus estramustine in metastatic hormone-refractory prostate cancer. 748 60

A total of 33 patients (median age, 44 years) with high-grade, adult soft-tissue sarcoma were treated with etoposide given at 600 mg/m2 in a 72-h continuous infusion and ifosfamide given at 1500 mg/m2 per day for 3 days every 3 weeks. Dose escalation/reduction was protocolled depending on the level of hematological toxicity observed in the preceding course. Overall, 90% of patients had metastatic disease, and the most common histologies were malignant fibrous histiocytoma and leiomyosarcoma. A median of 5 (range, 1-9) courses were given. Of 30 patients who were evaluable for response, 12 (40%) obtained a partial remission, and the median time to progression was 8 (range, 4-13) months. Grade 3-4 leukopenia and thrombocytopenia were seen after 89% and 8% of the courses, respectively; neutropenic fever was seen in half of the patients (15% of courses); and 32% of courses had to be postponed by 7 days or more due to myelosuppression. Dose reduction to below the standard had to be performed in 46% of courses, and dose escalation was achieved in only 13%. The reduced toxicity seen after the addition of granulocyte colony-stimulating factor (G-CSF) in five patients indicates that growth-factor support may enhance the dose intensity of the regimen. The results indicate significant activity for this regimen in adult soft-tissue sarcoma, which may in part be a result of the escalated dose and prolonged mode of administration of the phase-specific agent etoposide. As a result of this pilot series, a phase II study with ifosfamide, etoposide, and G-CSF in advanced adult soft-tissue sarcoma has been initiated by the Scandinavian Sarcoma Group.
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PMID:Treatment of advanced, high-grade soft-tissue sarcoma with ifosfamide and continuous-infusion etoposide. 753 39

A phase II trial was performed to assess the efficacy and toxicity of the combination mitoxantrone (MXN) and vinorelbine (VNR) as first-line chemotherapy for metastatic breast cancer. Forty-one patients with metastatic disease or local relapse recruited between March 1991 and April 1993 received a first-line chemotherapy treatment consisting in 12 mg/m2 intravenous (IV) bolus of MXN on day 1 followed by a 20-minute perfusion of 25 mg/m2 of VNR on days 1 and 8. Cycles were repeated every 21 days until evidence of disease progression or of severe toxicity. Thirty-seven patients were evaluable for response and all 41 for toxicity. An objective response was observed in 19 patients (51%; 95% confidence interval, 45 to 74%). The response was complete in a further 11 (30%). Median time to treatment failure was 9 months. Median survival was 14 months. There were no treatment-related deaths. Limiting toxicity was myelosuppression. Leukopenia occurred in 29 patients (71%) and was grade 3 or 4 in nine of these (15%). Grade 2 or 3 anemia was encountered in six patients (15%), grade 1 thrombocytopenia in one, neurotoxicity (constipation) in two, and grade 2 or 3 alopecia in 12 (29%). Nausea/vomiting requiring antiemetic treatment was experienced by only two patients (5%). There were two cases of septicemia treated by antibiotic therapy in hospital.
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PMID:[Combination of mitoxantrone-vinorelbine as first-line chemotherapy for metastatic breast carcinoma]. 765 48


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