Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methotrexate (MTX) in high doses (3 to 7.5 g/m2) with leucovorin rescue (HDMTX-LCV) can be delivered on a weekly basis in a setting of proper pharmacologic monitoring. Myelosuppression occurs in 28 per cent of the patients and in 8 per cent of the courses and usually results from delayed MTX excretion secondary to mild reversible nephrotoxicity. The incidence of tumor regression was 50 per cent in head and neck cancer; 59 per cent in non-Hodgkin's lymphoma; 40 per cent in small cell lung cancer; 24 to 50 per cent in breast cancer and 50 per cent in osteogenic carcinoma, for an over-all response rate of 39 per cent (70 of 178) in patients with disseminated cancer. HDMTX-LCV is not recommended for the conventional treatment of metastatic cancer because of the potential for toxicity and the fact that the response rates cited are probably not superior to those which can be achieved by conventional doses of MTX. However, the relative lack of myelosuppression and mucositis, when compared to conventional unrescued MTS, and the achievement of therapeutic concentrations of MTX in the central nervous system with the HDMTX-LCV program have led to its incorporation into clinical trials of combination chemotherapy.
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PMID:High dose methotrexate with leucovorin rescue. Rationale and spectrum of antitumor activity. 696 19

Several Louisiana parishes (counties) using the Mississippi River for their source of public drinking water have the highest mortality rates (1950-69) in the United States for several cancers. Therefore, a case-control mortality study on cancer of the liver, brain, pancreas, bladder, kidney, prostate, rectum, colon, esophagus, stomach, non-Hodgkin's lymphoma, multiple myeloma, leukemia, Hodgkin's disease, lung; breast and malignant melanoma, from 1960 to 1975 in South Louisiana parishes grouped for similarities in industrial characteristics, having approximately equal exposure of the population to surface and groundwater, was conducted. Noncancer deaths were randomly selected as controls and matched to the case death on age, race, sex, and year and parish group of death. Water source at death was assigned based on the residence at death and described as surface or ground and chlorinated or nonchlorinated. A significantly increased risk for surface, chlorinated water use was noted for rectal cancer. No risk could be demonstrated for colon cancer. The risk noted for bladder cancer by other investigators is not substantiated. Brain cancer risk appears to be associated with chlorinated groundwater, but this may be industrial confounding. Breast cancer demonstrated a slight, but significant, risk associated with surface chlorinated water. This risk, however, might be due to confounding of rural life style, early childbearing and large families with nonchlorinated water found in these settings. Chlorination risk for kidney cancer was not significant. No risk was observed in association with surface water for other cancers of the gastrointestinal or urinary tract. Multiple myeloma was significantly associated with a risk from ground water.
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PMID:Case-control cancer mortality study and chlorination of drinking water in Louisiana. 715 59

We have utilized a recently developed human tumor cloning system to screen for antitumor effects in vitro of a new anthracenedione derivative, Mitoxantrone. The object was to determine if the system is useful for pinpointing the types of tumors in patients which should be studied in early Phase II clinical trials. Tumors from 267 patients were placed in culture (20 different histological tumor types). One hundred seventy tumors both grew and formed enough colonies for drug sensitivity assays. Excellent in vitro antitumor activity was noted for Mitoxantrone against human adenocarcinoma of the lung, small cell lung cancer, melanoma, and biliary tree cancer. Good antitumor activity was noted against breast cancer, ovarian cancer, non-Hodgkin's lymphoma, head and neck cancer, squamous cell lung cancer, soft tissue sarcoma, gastric cancer, and hepatomas. The drug showed no in vitro activity against colon cancer. These data indicate that Mitoxantrone has a wide spectrum of in vitro antitumor activity. A comparison of these in vitro results with the results of Phase II clinical trials with the drug should allow an evaluation of the utility of the human tumor cloning system for predicting clinical antitumor activity of a new compound.
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PMID:Activity of mitoxantrone in a human tumor cloning system. 721 52

The prognostic effect of weight loss prior to chemotherapy was analyzed using data from 3,047 patients enrolled in 12 chemotherapy protocols of the Eastern Cooperative Oncology Group. The frequency of weight loss ranged from 31 percent for favorable non-Hodgkin's lymphoma to 87 percent in gastric cancer. Median survival was significantly shorter in nine protocols for the patients with weight loss compared to the patients with no weight loss. Chemotherapy response rates were lower in the patients with weight loss, but only in patients with breast cancer was this difference significant. Decreasing weight was correlated with decreasing performance status except for patients with pancreatic and gastric cancer. Within performance status categories, weight loss was associated with decreased median survival. The frequency of weight loss increased with increasing number of anatomic sites involved with metastases, but within categories of anatomic involvement, weight loss was associated with decreased median survival. These observations emphasize the prognostic effect of weight loss, especially in patients with a favorable performance status or a limited anatomic involvement with tumor.
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PMID:Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. 742 38

A phase II study of vindesine in 41 evaluable patients demonstrated the drug to be active in heavily pretreated patients with breast cancer, non-Hodgkin's lymphoma, and other tumors. There were two partial responses in 11 patients with breast cancer (18%) and five partial responses and one complete response in 11 patients with non-Hodgkin's lymphoma (40%). Other responses were seen in small cell carcinoma of the lung, ovarian carcinoma, and Hodgkin's disease. Prior vinca exposure did not adversely affect the response rate. Neutropenia was dose-limiting. Neurotoxic effects occurred in 10% of the patients. A high incidence of local tissue reactions at the injection site (27%) could be reduced by a careful administration technique. Vindesine should be studied further in combination with other agents.
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PMID:Phase II trial of vindesine in the treatment of lymphomas, breast cancer, and other solid tumors. 744 18

G-CSF and GM-CSF enhance the rate of neutrophil engraftment in autologous bone marrow transplantation (ABMT) without significantly affecting platelet engraftment. Peripheral blood progenitor cells (PBPC) may enhance rates of engraftment of both neutrophils and platelets. We treated 49 patients undergoing ABMT with a course of G-CSF to obtain PBPC and infused these cells post-transplant with G-CSF in an attempt to determine factors which might correlate with enhanced BM engraftment. Forty-nine patients with Hodgkin's disease, non-Hodgkin's lymphoma or breast cancer undergoing unpurged ABMT were studied. G-CSF priming consisted of an outpatient 8 day course of 5 micrograms/kg/day followed by three leukaphereses (on day 5, 7 and 8) to collect PBPC. Patients then received a chemotherapeutic BMT preparative regimen followed by an infusion of PBPC, autologous BM and the reinstitution of G-CSF (16 micrograms/kg/day). BM engraftment was rapid. The median time to achieve 0.5 x 10(9)/l neutrophils was 10 days compared with a historical BMT control patient population receiving the same preparative regimens of 19 days (p = 0.001). Time to achieve a platelet count of 20 x 10(9)/l was 16 days compared with a historical control of 22 days (p = 0.001). Neutrophil engraftment occurred in all patients by day +14. Marrow engraftment correlated with the total number of CD34+ cells infused as well as the total number of mononuclear cells infused but not the total number of CD34+/CD33- cells infused. The amount of total blood volume pheresed significantly correlated with yield of total mononuclear cells. Prior exposure to radiation therapy negatively correlated with progenitor cell yield.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:G-CSF primed peripheral blood progenitor cells in autologous bone marrow transplantation: parameters affecting bone marrow engraftment. 751 Oct 16

Peripheral blood progenitor cell (PBPC) populations used for transplantation were analyzed for the presence of CD34+ cells, colony-forming cells (initial CFC), and long-term culture initiating cells (LTC-IC) cultured on irradiated stroma for 5 weeks. Thirty-eight leukapheresis products were studied from 11 patients with breast cancer, 2 with non-Hodgkin's lymphoma and 1 with ovarian cancer harvested during recovery from either cyclophosphamide (CY) chemotherapy or cyclophosphamide-VP16 with G-CSF (CY-VP-G). CY-VP-G products had a threefold higher median number of mononuclear cells collected, a fivefold higher median concentration of CD34 and LTC-IC and a threefold higher concentration of initial-CFC when compared with CY products. CY-VP-G products had a significantly higher ratio of CFU-GM to BFU-E than the CY-mobilized products. Significant correlations of r = 0.89 and r = 0.68 were observed when comparing CD34 and CFC in products from CY or CY-VP-G patients, respectively. Analysis of the regression lines indicated that slopes of these regression lines were significantly different with a ratio of CD34 to initial CFC of 15:1 in the CY-VP-G products versus 5.2:1 with the CY products. These data indicate a higher cloning efficiency of the CD34+ population in the products from CY-mobilized patients. Significant correlations of r = 0.9 (CY) and r = 0.53 (CY-VP-G) were observed when the initial CD34 concentration and the LTC-IC were compared. Comparison of initial CFC with LTC-IC also showed significant correlations (r = 0.94, CY; r = 0.58, CY-VP-G) in samples from both patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation of colony-forming cells, long-term culture initiating cells and CD34+ cells in apheresis products from patients mobilized for peripheral blood progenitors with different regimens. 751 60

The clinical usefulness of Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF, Filgrastim, GRAN) was evaluated in patients with leukopenia and neutropenia following chemotherapy for non-Hodgkin's lymphoma, lung cancer and breast cancer. During chemotherapy when patients' leukocyte count (WBC) fell below 4.0 x 10(9)/L.rhG-CSF(GRAN) at a dose of 75 micrograms/body.day was given subcutaneously 48 hours after the termination of chemotherapy. The results indicated that rhG-CSF(GRAN) could elevate nadirs of WBC and significantly shortened leukopenic period with WBC below 4.0 x 10(9)/L and expedited the recovery of WBC. rhG-CSF (GRAN)'s side effects were mild.
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PMID:[Clinical study of recombinant human granulocyte colony stimulating factor (rhG-CSF) on leukopenia induced by chemotherapy in cancer patients]. 752 73

Twenty-eight patients with poor prognosis acute myeloid leukemia (AML) received therapy with two courses of fludarabine 30 mg/m2/day + ara-C 2 g/m2/day (days 1-5) and G-CSF 5 mg/kg/day (FLAG) (from day 0 to polymorphonuclear recovery). Eighteen patients were considered 'refractory' (eight primarily resistant, five relapsing within 6 months of initial remission, or at a second relapse; five relapsing after an autologous bone marrow transplantation procedure. Ten cases were defined 'secondary' AML (diagnosis of AML made after a preexisting diagnosis of: myelodysplastic syndrome: five cases; myelodysplastic syndrome after therapy for breast cancer: one case; previously untreated, and concomitant, non-Hodgkin's lymphoma: two cases; Hodgkin's disease treated with chemoradiotherapy: one case). Overall, 15 patients (58%) achieved a complete remission (CR). Two patients died of infection during induction, and 11 had resistant disease. Analyzing the data in relation to selected host and disease characteristics, the response varied widely. The highest CR rates (89%) were obtained in secondary AML; in particular, two cases of 'second-primary' (concomitant with low-grade non-Hodgkin's lymphoma) AML obtained CR for both diseases. Refractory AML differed widely for response: high CR rate (75%), although with short mean CR duration for primary resistance AML, and very poor response (11% CR) for relapsed (early, second, after ABMT) cases. Interestingly, a slow kinetic of leukemic growth in vivo before FLAG administration was significantly related to the response and outcome (p = 0.0002). Hematological and nonhematological toxicities were acceptable. In conclusion, the FLAG regimen has significant antileukemic activity and acceptable toxicity especially in secondary AML, both with and without coexisting lymphoid malignancy.
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PMID:FLAG (fludarabine + high-dose cytarabine + G-CSF): an effective and tolerable protocol for the treatment of 'poor risk' acute myeloid leukemias. 752 88

Factors affecting mobilization and engraftment were analysed in 54 patients undergoing transplant using autologous PBSCs mobilized with high-dose recombinant granulocyte stimulating factor (rhG-CSF). Patients received 5-7 d of rhG-CSF, 16 micrograms/kg/d, administered subcutaneously. PBSCs were harvested by leukapheresis using automated continuous-flow blood cell separators beginning on day 4 of rhG-CSF, processing 10 litres of whole blood, for 2-6 consecutive days. Transplants were performed for the following diseases: breast cancer (n = 22), non-Hodgkin's lymphoma (n = 18), multiple myeloma (n = 7) and other (n = 7). Engraftment was rapid with patients reaching a neutrophil count of 1 x 10(9)/l a median of 12 d (range 9-22) after transplant. Platelets > 20 x 10(9)/l independent of transfusion support were achieved a median of day 10 (range 7-60) after infusion. Multiple factors potentially influencing engraftment were examined using a Cox regression model. The number of CD34+ cells per kg was highly correlated with the time to achievement of granulocyte and platelet recovery (P < 0.012, 0.0001). The use of a post-infusion growth factor and a radiation preparative regimen was important for neutrophil recovery, and a diagnosis of breast cancer was important for platelet recovery. In an analysis by linear regression of the logarithm of CD34+ cells collected, lower age, marrow without disease, no prior radiation, and lower number of prior chemotherapy regimens, were important factors influencing larger numbers of CD34+ cells in collections.
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PMID:Peripheral blood stem cells (PBSCs) collected after recombinant granulocyte colony stimulating factor (rhG-CSF): an analysis of factors correlating with the tempo of engraftment after transplantation. 753 30


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