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)

The murine C1300 neuroblastoma model has been evaluated as a possible model for children with widespread metastatic disease. Drug toxicity studies were conducted in adult A/J mice with various doses of antitumor agents. Adriamycin, BCNU, bleomycin, guanazole, acronycine, isophosphamide, DTIC, ICRF-159, cyclophosphamide, vincristine, and vinblastine were adminstered intraperitoneally to random groups of normal mice. After identification of appropriate doses, chemotherapy studies were conducted with varius regimens of drugs. Chemotherapy was administered to adult A/J mice when their subcutaneously implanted tumors measured 1.0-1.7 cm in diameter. Antitumor drugs can be classified into three groups according to drug efficacy. BCNU, cyclophosphamide, and isophosphamide were extremely active. Cytosine arabinoside was reported to be active against this murine tumor in a previous publication. Drugs with minimal activiyt which deserve further evaluation included adriamycin, guanazole, ICRF-159, DTIC, and vinblastine. Inactive drugs were acronycine, bleomycin, 5-fluorouracil, and vincristine. These experiments suggest that children with metastatic neuroblastoma may respond to cyclophosphamide, isophosphamide, and BCNU, while DTIC, adriamycin, ICRF-159, guanazole, and the vinca alkaloids may also be effective. The results suggest that agents selected by the C1300 model should be given adequate clinical trials.
 ...
PMID:Murine neuroblastoma: further evaluation of the C1300 model with single antitumor agents. 120

Eighty-two patients with metastatic tumor received a therapeutic regimen consisting of BCNU, 100 mg/m2, and cyclophosphamide, 400 mg/m2, both intravenously on day 1, followed by adriamycin, 40 mg/m2, on day 2. Treatment was repeated every 4 weeks. Of 14 evaluable patients with adenocarcinoma of the breast, all resistant to previous chemotherapy and 12 resistant to a five-drug combination chemotherapy program, 12 had objective responses of which seven were good partial responses. Osseous, visceral, and cutaneous metastases responded equally well. Overall, 53% of 68 evaluable patients had objective responses, and 32% had complete or good partial responses. The most encouraging results were in patients with carcinoma of the head and neck, ovarian carcinoma, and multiple myeloma refractory to standard therapy. Significant responses were observed in previously untreated patients with epidermoid carcinoma of the lung, carcinoma of the prostate, and carcinoma of undermined primary. Remissions lasted a median of 5 months. Myelosuppression was moderate in degree and was maximal 2 weeks after treatment. Cumulative thrombocytopenia was apparent but not dose limiting with repeated courses.
 ...
PMID:Adriamycin, 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU-NSC 409462), and cyclophosphamide in refractory adenocarcinoma of the breast and other tumors. 125 1

The efficacy of the association of recombinant interleukin-2 (rIL-2) with chemotherapy has been investigated on an experimental model representative of clinical tumours, i.e. on post-surgical spontaneous metastases of a non-immunogenic tumour. We used the M5076 ovarian reticulum cell sarcoma, which metastasizes to the liver after intra-footpad implantation. Such a tumour appeared to be non-immunogenic by a variety of commonly used in vivo assays. Four clinically widely employed drugs, i.e. doxorubicin, cis-diamminedichloroplatinum II, cyclophosphamide and 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), were tested and BCNU proved to be the most effective one when administered as single injection at the maximum tolerated dose (33 mg/kg i.p.) 1 day after tumour excision. When moderate doses of rIL-2 (6 x 10(5) IU in three injections per day for 5 days) were administered at three different intervals after BCNU, namely before the nadir of white blood cells (1 day after BCNU), at the nadir (3 days after BCNU) or at recovery (6 days after BCNU), no increase in BCNU antitumour activity was observed. The same results were obtained by administering rIL-2 for 5 days before BCNU. Higher doses of rIL-2 (1.2 x 10(6) IU in three injections per day for 5 days), which were always well tolerated in sham-excised non-tumour-bearing mice, proved lethal in two out of four experiments in tumour-bearing animals. In the two experiments in which no lethality was observed, the administration of high doses of rIL-2 1 or 6 days after BCNU significantly increased the antitumour activity of BCNU alone. rIL-2 alone was not active even when administered at high doses. These results indicate that high but not moderate doses of rIL-2 may increase the activity of BCNU against a non-immunogenic tumour. Moreover, they suggest that rIL-2 tolerability is reduced in tumour-bearing mice.
 ...
PMID:Postsurgical adjuvant chemoimmunotherapy with recombinant interleukin-2 and 1,3-bis-(2-chloroethyl)-1-nitrosourea on spontaneous metastases of a non-immunogenic murine tumour. 156 15

Seventeen patients with chemotherapy-resistant metastatic sarcoma were treated with whole body hyperthermia (WBH) combined simultaneously with 1-3-Bis(2-chloroethyl)-1-nitrosourea (BCNU). All of the patients had chemotherapy resistant metastases to major organ sites. Patients were heated to 41.8-42.0 degrees C for 2 h using an insulated blanket heating technique. Two patients (12%) experienced partial responses (PR). In addition, four objective tumour responses (OR) lasting more than 4 months were documented. One patient with previously rapidly growing chondrosarcoma pulmonary metastases experienced stable disease (SD) for 38 months from the onset of treatment. Median survival of seven patients with responding tumours (PR, OR and SD) compared with 10 patients with progressive disease was 15 versus 2 months, respectively. Cumulative thrombocytopenia was a therapy-limiting toxicity of the combined treatment, and occurred in six of seven patients. Acute toxicities attributable to WBH alone included transient thrombocytopenia in all patients, non-cardiogenic pulmonary oedema in two patients, and mild hypotension in five patients. Acute granulocytosis was observed in all patients. No treatment related deaths occurred. These data suggest that WBH combined with chemotherapy is associated with disease response in patients with chemotherapy-resistant, widely disseminated sarcoma metastases.
 ...
PMID:Chemotherapy resistant sarcoma treated with whole body hyperthermia (WBH) combined with 1-3-bis(2-chloroethyl)-1-nitrosourea (BCNU). 160 34

Between 2/87 and 2/91, 49 women with operable breast cancer involving greater than or equal to 10 axillary nodes were treated following mastectomy, with four cycles of Cyclophosphamide, Adriamycin, 5FU, followed by high doses of Cyclophosphamide, Cisplatin, Carmustine (HDCT) with autologous bone marrow transplant support. Forty patients received local-regional radiotherapy (generally to the chest wall, internal mammary, supraclavicular, +/- axillary nodal areas; minimum 44-50 Gy, 1.8-2 Gy/fraction, +/- 10-15 Gy scar boost; standard radiation techniques). The first nine patients did not receive local-regional radiotherapy. Three developed a local-regional failure (6-12 months after HDCT); six are without evidence of disease. Local-regional radiotherapy (LR XRT) was delivered to the subsequent 40 patients following HDCT+autologous bone marrow transplant. Six received less than 44 Gy of the planned local-regional radiotherapy due to significant toxicity and one of these failed locally. Only one local failure was observed among the 34 patients who received greater than or equal to 44 Gy. Two additional patients developed distant metastases. None of these 40 patients have failed in the axilla despite the fact that the axilla was irradiated in only 18 cases. Overall, 36/40 (90%) of these patients are without evidence of disease 4-30 months following HDCT (approximately 10-36 months after mastectomy, median 22 months). Radiotherapy was interrupted or discontinued because of progressive dyspnea, thrombocytopenia, or neutropenia in nine patients. Further studies to determine the roles of local-regional radiotherapy and HDCT in the development of these toxicities are underway. These encouraging results suggest that HDCT + autologous bone marrow transplant+local-regional radiotherapy may improve the survival rate in these high risk patients. A national randomized study to test the efficacy of this HDCT regimen is currently underway (Cancer and Leukemia Group B#9082 and Southwest Oncology Group #9114).
 ...
PMID:Post-mastectomy radiotherapy following adjuvant chemotherapy and autologous bone marrow transplantation for breast cancer patients with greater than or equal to 10 positive axillary lymph nodes. Cancer and Leukemia Group B. 163 44

Fourteen patients with small cell carcinoma of the lung in relapse or with disease refractory to chemotherapy were treated with carmustine (BCNU) at doses of 600 to 1000 mg/m2 intravenously followed by autologous bone marrow transplantation. All patients previously were treated with cyclophosphamide, doxorubicin, vincristine, and etoposide. Seven of the 14 patients responded to the high-dose BCNU (50% response with 95% confidence limits ranging from 23% to 77%). Three patients had a complete response, and four had a partial response. Regrowth of tumor occurred within 60 days of treatment in the responding patients. Death occurred in six patients before the recovery of the platelet count to 50,000 cells/microliters. Although the response rate was high, the toxicity was excessive. In the dosage range of 600 to 1000 mg/m2 in heavily pretreated patients, BCNU is not recommended, but additional investigation may be warranted in patients with central nervous system metastases who previously were treated with radiation therapy.
 ...
PMID:High-dose carmustine and autologous bone marrow reinfusion in the treatment of refractory or relapsed small cell lung carcinoma. 164 84

In a consecutive series of studies, 164 patients with symptomatic and/or visceral metastatic malignant melanoma were treated with single agent vindesine, high dose melphalan with autologous bone marrow transplantation (AMBT), high dose BCNU with ABMT or the BOLD (bleomycin, vincristine, CCNU and DTIC) combination. The high dose treatments and the combination chemotherapy resulted in significantly higher response rates but no prolongation of survival. Factors associated with longer survival included the absence of visceral metastases, the absence of bulky disease and good performance status. For all treatments, life table estimates of survival at 1 and 2 years were only 10% and 4% respectively.
 ...
PMID:Chemotherapy for malignant melanoma: combinations and high doses produce more responses without survival benefit. 169 22

Between January 1983 and April 1989, 61 patients with brain metastases of primary breast cancer were treated in the Robert Janker Clinic. To optimize the overall response rates, a simultaneous combination of radiation and chemotherapy was used. The patients median age was 49 (range, 30-67) years and the median performance score, 1 (0-2). The average interval between the diagnosis of the primary tumour and the brain metastases was 38 (range, 3-144) months. A total of 82% of the patients had multiple cerebral metastases. All patients had been pretreated with primary surgery; 79%, with radiation; 74%, with chemotherapy; and 64%, with hormones. Radiotherapy was given using a cobalt 60 machine. The whole brain was irradiated in daily fractions of 1.5 Gy, up to a total dose of 45 Gy. Using a split-course technique, this dose was given in three courses simultaneously with the chemotherapy. The chemotherapeutic regimen consisted of ifosfamide given daily for 5 days at 2 g/m2 and the nitrosourea derivative carmustine (BCNU) given at 30 mg/m2 on 3 days. The toxicity of the treatment was moderate; no haemotological or gastro-intestinal complications occurred. Complete and mostly irreversible alopecia occurred in all cases. All patients received a cranial computerized tomographic (CT) scan prior to and after treatment. According to the criteria of the International Union Against Cancer (UICC), there was a complete remission (CR) in 20% of the patients and a partial remission (PR) in 45%; 20% had a minor remission (MR) and 7% showed no change (NC) in the tumour. Another 7% of the patients experienced a progression of their metastases (PD). The median survival was 8 months for all patients and 12 months for those showing a CR.
 ...
PMID:Palliative radio-chemotherapy with ifosfamide and BCNU for breast cancer patients with cerebral metastases. A 5-year experience. 169 18

Cerebral metastases of malignant melanoma are correlated with a very poor prognosis. Surgery of an isolated metastase can lead to a long survival but the brain lesions are frequently numerous and associated with an extracerebral diffusion. Dacarbazine (DTIC) gives a mean response rate of 21% on visceral localisations but doesn't cross the blood brain barrier (BBB). Neither do the biological response modifiers like Interleukin 2 (Il2) that leads to 25% response rate in disseminated melanoma. Nitrosoureas like carmustine (BCNU) and semustine (CCNU) have been investigated in different non randomised studies and the clinical results didn't illustrate their theorical ability to cross the BBB. Radiotherapy is also used as a palliative therapy with 7 to 16 weeks survival. Fotemustine (muphoran), a new amino acid linked nitrosourea, can give a response rate up to 28.2% in patients with cerebral metastases and the increased survival of responding patients is significant. The availability of this new drug may suggest associations with surgery and radiotherapy in the future to improve the survival of such patients.
 ...
PMID:[Brain metastases of malignant melanomas]. 185 2

Primary and metastatic hepatic tumours--evaluation of tumour regression or response under regional cytostasis with sonography and fine needle puncture histology. The results obtained through the use of regional liver perfusion with a 5-FU-BCNU application on non-resectable hepatic metastases of colorectal tumours following primary curative removal of the primary tumour and primary hepatocellular carcinomas display comparable results to those specified in the literature after the use of 5-FUDR. The effectivity of the cytostasis regime is checked using histological criteria. The ultrasonically guided fine needle puncture can prove the success of the cytostasis regime on the basis of cytomorphologic criteria more reliably than has been the case up to now. Patients displaying histological signs of tumour regression have a significantly longer survival time than those displaying no signs of regression (12 +/- 9.2 vs 4.5 +/- 2.2 months; p less than 0.05).
 ...
PMID:[Primary and metastatic liver tumors--evaluation of tumor regression and response with regional cytostatic drug therapy by sonography and fine needle puncture histology]. 216 47


<< Previous 1 2 3 4 5 6 7 8 Next >>