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)

We treated 115 patients in a phase I/II dose-escalation study of ifosfamide/carboplatin/etoposide (ICE) followed by autologous stem cell rescue. Patients treated had a variety of diagnoses, including breast cancer (high-risk stage II disease with eight or more positive nodes, stage III disease, and responsive metastatic disease), non-Hodgkin's lymphoma, Hodgkin's disease, acute leukemia in first remission, and various solid tumors that were responsive to induction therapy. Patients received autologous bone marrow stem cells or peripheral blood stem cells primed by one of several methods. The maximum tolerated dose of ICE was determined to be ifosfamide 20,100 mg/m2, carboplatin 1,800 mg/m2, and etoposide 3,000 mg/m2 when administered as a 6-day regimen. The dose-limiting toxicities included acute renal failure, severe central nervous system toxicity, and "leaky capillary syndrome" with hypoalbuminemia, profound fluid overload, and pulmonary insufficiency. Analysis of hematologic recovery based on stem cell source and influence of hematopoietic growth factor administration was undertaken. Hematopoietic growth factor use significantly reduced neutrophil engraftment time for patients receiving bone marrow stem cells, with evidence of earlier recovery times for patients receiving granulocyte colony-stimulating factor compared with granulocyte-macrophage colony-stimulating factor. Neutrophil recovery times varied based on the source of stem cells used, with the earliest engraftment times seen for patients receiving peripheral blood stem cells primed with cyclophosphamide and granulocyte colony-stimulating factor. Platelet recovery times were not statistically different for any of the subsets. In conclusion, the maximum tolerated dose of ICE has been defined, and the source of stem cells and the use of hematopoietic growth factors influence hematopoietic recovery.
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PMID:High-dose ifosfamide/carboplatin/etoposide: maximum tolerable doses, toxicities, and hematopoietic recovery after autologous stem cell reinfusion. 752 92

Paclitaxel is a new anticancer agent with a novel mechanism of action. It promotes polymerisation of tubulin dimers to form microtubules and stabilises microtubules by preventing depolymerisation. In noncomparative trials, continuous infusion of paclitaxel 110 to 300 mg/m2 over 3 to 96 hours every 3 to 4 weeks produced a complete or partial response in 16 to 48% of patients with ovarian cancer and 25 to 61.5% of patients with metastatic breast cancer, many of whom were refractory to treatment with cisplatin or doxorubicin, respectively. 23 to 100% of patients with ovarian cancer achieved complete or partial responses with paclitaxel in combination with cisplatin, carboplatin, cyclophosphamide, altretamine and/or doxorubicin. Similarly, response rates of 30 to 100% were observed with paclitaxel plus doxorubicin, cisplatin, mitoxantrone and/or cyclophosphamide in patients with metastatic breast cancer. Comparative trials in patients with advanced ovarian cancer showed paclitaxel therapy to produce greater response rates than treatment with parenteral hydroxyurea (71 vs 0%) or cyclophosphamide (when both agents were combined with cisplatin) [79 vs 63%]. Paclitaxel was also more effective than mitomycin in 50 patients with previously untreated breast cancer (partial response in 20 vs 4% of patients). Paclitaxel therapy also produced promising results in patients with advanced squamous cell carcinoma of the head and neck, malignant melanoma, advanced non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), germ cell cancer, urothelial cancer, oesophageal cancer, non-Hodgkin's lymphoma or multiple myeloma, and was successfully combined with cisplatin, carboplatin and/or etoposide in patients with NSCLC, SCLC or advanced squamous cell carcinoma of the head and neck. Hypersensitivity reactions were initially a concern with administration of paclitaxel, although current dosage regimens have reduced the incidence of these events to less than 5%. The major dose-limiting adverse effects of paclitaxel are leucopenia (neutropenia) and peripheral neuropathy. Other haematological toxicity was generally mild. Cardiac toxicity was reported in small numbers of patients and most patients developed total alopecia. Several aspects of paclitaxel use remain to be clarified, including the optimal treatment schedule and infusion time, confirmation of the tolerability profile and efficacy of combination regimens in an expanded range of malignancies. Long term follow-up of paclitaxel recipients will also allow the effects of the drug on patient survival to be determined. Nevertheless, paclitaxel is a promising addition to the current therapies available, with significant activity reported in patients with advanced ovarian or breast cancer or other types of tumors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Paclitaxel. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of cancer. 753 Jun 32

Peripheral blood progenitor cells (PBPC) can be mobilized using cytotoxic chemotherapy and cytokines. There is a substantial variability in the yield of hematopoietic progenitor cells between patients. We were looking for predictive parameters indicating a patient's response to a given mobilization regimen. Multiparameter flow-cytometry analysis and clonogenic assays were used to examine the hematopoietic progenitor cells in bone marrow (BM) and peripheral blood (PB) before filgrastim (R-metHuG-CSF; Amgen, Thousand Oaks, CA)-supported chemotherapy and in PB and leukapheresis products (LPs) in the recovery phase. Fifteen patients (four with high-grade non-Hodgkin's lymphoma [NHL], two with low-grade NHL, two with Hodgkin's disease, two with multiple myeloma, three with breast cancer, one with ovarian cancer, and one with germ cell tumor) were included in this study. The comparison of immunofluorescence plots showed a homogenous population of strongly CD34+ cells in steady-state and mobilized PB whereas in steady-state BM, the CD34+ cells ranged from strongly positive with continuous transition to the CD34- population. Consistent with the similarity in CD34 antigen expression, a correlation analysis showed steady-state PB CD34+ cells (r = .81, P < .001) and colony-forming cells (CFCs; r = .69, P < .01) to be a measure of a patient's mobilizable CD34+ cell pool. Individual estimates of progenitor cell yields could be calculated. With a probability of 95%, eg, 0.4 steady-state PB CD34+ cells x 10(6)/L allowed to collect in six LPs 2.5 x 10(6) CD34+ cells/kg, the reported threshold-dose of progenitor cells required for rapid and sustained engraftment after high-dose therapy. For the total steady-state BM CD34+ cell population, a weak correlation (r = .57, P < .05) with the mobilized CD34+ cells only became apparent when an outlier was removed from the analysis. Neither the CD34+ immunologic subgroups defined by the coexpression of the myeloid lineage-associated antigens CD33 or CD45-RA or the phenotypically primitive CD34+/HLA-DR- subset nor the BM CFC count had a predictive value for the mobilization outcome. This may be caused by the additional presence of maturing progenitor cells in BM, which express lower levels of the CD34 antigen and do not circulate. Our results permit us to recognize patients who are at risk to collect low numbers of progenitor cells and those who are likely to achieve sufficient or high progenitor cell yields even before mobilization chemotherapy is administered.
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PMID:Peripheral blood progenitor cell (PBPC) counts during steady-state hematopoiesis allow to estimate the yield of mobilized PBPC after filgrastim (R-metHuG-CSF)-supported cytotoxic chemotherapy. 860 80

CD44 is a transmembrane glycoprotein occurring in several isoforms with different extracellular regions. The various transcripts are encoded by one gene locus containing 20 exons, of which at least 10 can be alternatively spliced in nascent RNA. Isoforms encoded by the variant exons (termed CD44v) are highly restricted in their distribution in nonmalignant tissue as opposed to the standard form of CD44 (CD44s) abundant in many tissues. Specific variant isoforms containing exon 6v have been shown to render nonmetastatic rat tumor cells metastatic. Based on the prominent role in rat metastasis formation, CD44v isoforms were suggested to be involved in human tumor progression. Correlations between prognosis and expression of CD44v have been reported for gastric and colon carcinoma, for non-Hodgkin's lymphoma, and recently for breast carcinoma. We evaluated the expression of CD44 isoforms in node-positive (n = 119) and node-negative (n = 108) cases of breast carcinoma by immunohistochemistry using CD44v exon-specific mAbs. In a subset of 43 cases of high-risk patients, reverse transcription-PCR was used to determine the exon composition of the transcripts. Protein and RNA expression data were probed statistically for their correlation to survival of the patients and clinical risk factors. In contrast to recently published data (M. Kaufmann et al., Lancet, 345: 615-619, 1995), in our cohort disease-free and overall survival data did not indicate significant correlations with the expression of the analyzed isoforms in univariate and multivariate analyses. Comparison of CD44 protein expression with established clinical risk factors for survival such as tumor size (pT1+pT2) and histological grading revealed correlations with the presence of CD44s (P = 0.02 and P = 0.03, respectively) and CD44-9v (P = 0.05 for histological grading). Carcinoma tissues with elevated estrogen and progesterone receptor levels showed positive correlation with CD44-6v (P = 0.001), while a trend for significant coexpression of CD44s and CD44-9v isoforms was observed in estrogen receptor-positive tissues (P = 0.08 and 0.06, respectively). In breast cancer, CD44s, CD44-9v, and CD44-6v are apparently markers for cellular differentiation but not for tumor progression. Our data suggest that steroid hormone receptors may be associated with the in vivo expression of CD44-6v-containing isoforms in human mammary carcinoma.
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PMID:CD44 isoforms correlate with cellular differentiation but not with prognosis in human breast cancer. 758 12

Since the beginning of its clinical development 20 years ago, etoposide has become an important and widely used agent in clinical oncology. Its integral role in the treatment of germ cell tumors and small-cell lung cancer seems unlikely to diminish in the future, and its use in non-Hodgkin's lymphoma and in various high dose regimens will probably continue to increase. Active investigation continues regarding the optimal dose and schedule of etoposide, and it is likely that these investigations will result in further improvement of its clinical activity in patients with sensitive tumor types. Continued clinical investigation may result in the identification of active etoposide containing combination regimens for ovarian cancer, breast cancer, and some of the childhood malignancies. Exciting possibilities for the future include exploration of etoposide in combination with the topoisomerase I inhibitors, as well as the development of drugs to reverse drug resistance. During the next 10 years, the applications and importance of this unique drug will continue to increase.
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PMID:Etoposide: twenty years later. 761 47

Peripheral blood mononuclear cells (PBMC) were collected after the administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and used as the sole source of hematopoietic stem cells after myeloablative therapy with busulfan (Bu) and cyclophosphamide (Cy). These studies were performed in 12 patients with malignancies (4 non-Hodgkin's lymphoma, 5 breast cancer, 1 testicular carcinoma, 1 Wilm's tumor, and 1 undifferentiated carcinoma) who had bone or bone marrow disease or had low marrow cellularity. rhG-CSF (16 micrograms/kg/d) was administered for 5 to 7 days by subcutaneous injection and PBMC were collected for 2 to 5 days beginning on day 4 after initiation of rhG-CSF, using continuous-flow blood-cell separators that processed 10 to 12 L of whole blood. From a median of three collections, a mean of 24.0 x 10(8) (+/- 10.5 SD) total nucleated cells/kg containing 12.6 x 10(8) (+/- 4.5 SD) mononuclear cells/kg, 7.3 x 10(6) (+/- 4.3 SD) CD34+ cells/kg and 20.5 x 10(4) (+/- 28.1 SD) granulocyte-macrophage colony-forming units (CFU-GM)/kg were harvested and cryopreserved. After the administration of Bu 14 to 17 mg/kg and Cy 120 to 150 mg/kg, PBMC were thawed and infused. One patient received rhG-CSF after the infusion of PBMC and the remaining 11 patients did not receive postinfusion growth factors. Mean days to recovery of neutrophil levels of 0.1, 0.5, and 1.0 x 10(9)/L were 11.4 (range, 9 to 13), 12.7 (range, 10 to 15), and 13.6 (range, 11 to 16) and the mean day to platelet transfusion independence was 13.3 (range, 7 to 49). Time to recovery of neutrophils to 0.5 and 1.0 x 10(9)/L and platelets to 20 x 10(9)/L was more rapid than in historical patients treated with Bu and Cy who received marrow alone or marrow followed by the posttransplant administration of rh-G or GM-CSF. No graft failures have been observed with a follow-up of 4 to 12 months. These results indicate that PBMC collected after rhG-CSF lead to rapid hematopoietic recovery after myeloablative chemotherapy.
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PMID:Autologous transplantation with peripheral blood mononuclear cells collected after administration of recombinant granulocyte stimulating factor. 768 25

Epirubicin is the 4' epimer of the anthracycline antibiotic doxorubicin, and has been used alone or in combination with other cytotoxic agents in the treatment of a variety of malignancies. Comparative and noncomparative clinical trials have demonstrated that regimens containing conventional doses of epirubicin achieved equivalent objective response rates and overall median survival as similar doxorubicin-containing regimens in the treatment of advanced and early breast cancer, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), non-Hodgkin's lymphoma, ovarian cancer, gastric cancer and nonresectable primary hepatocellular carcinoma. Recently, dose-intensive regimens of epirubicin have achieved high response rates in a number of malignancies including early and advanced breast cancer and lung cancer. The major acute dose-limiting toxicity of anthracyclines is myelosuppression. In vitro and clinical studies have shown that, at equimolar doses, epirubicin is less myelotoxic than doxorubicin. The lower haematological toxicity of epirubicin, as well as the recent introduction of supportive measures such as colony-stimulating factors, has allowed dose-intensification of epirubicin-containing regimens, which is particularly significant because of the definite dose-response relationship of anthracyclines. Cardiotoxicity, which is manifested clinically as irreversible congestive heart failure and/or cardiomyopathy, is the most important chronic cumulative dose-limiting toxicity of anthracyclines. Epirubicin has a lower propensity to produce cardiotoxic effects than doxorubicin, and its recommended maximum cumulative dose is almost double that of doxorubicin, thus allowing for more treatment cycles and/or higher doses of epirubicin. In summary, dose-intensive epirubicin-containing regimens, which are feasible due to its lower myelosuppression and cardiotoxicity, have produced high response rates in early breast cancer, a potentially curable malignancy, as well as advanced breast, and lung cancers. Furthermore, there is evidence to suggest that improved response rates can improve quality of life in some clinical settings, but whether this leads to prolonged survival has not yet been determined. Recently implemented supportive measures such as colony-stimulating factors, prophylactic antimicrobials and peripheral blood stem cell support may help achieve other potential advantages of dose-intensive epirubicin-containing regimens such as reductions in morbidity and length of hospital admissions.
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PMID:Epirubicin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in cancer chemotherapy. 768 69

Techniques to assay minimal residual disease are available for most patients with acute lymphoblastic leukemia, non-Hodgkin's lymphoma, breast cancer, Ewing's sarcoma, and others. Today, a few such tests exist for acute myelogenous leukemia (AML). This review evaluates the tests available for assessing minimal residual disease in AML: morphology, growth in vitro, cytogenetics, magnetic resonance imaging, polymerase chain reaction (PCR)-based assays for translocation products, and multiparameter flow cytometry. Of these, multiparameter flow cytometry appears most promising. Studies using multiparameter flow cytometry to identify leukemic cells by aberrant antigen expression have reported a high positive predictive value with regard to the incidence of relapse. In addition, the test is specific, rapid, inexpensive, and applicable to a sufficiently broad group of patients, allowing its use outside of the research laboratory setting. Judicious use of some of the available assays singly or in combination should identify patients harboring residual leukemic cells.
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PMID:Detection of minimal residual disease in acute myelogenous leukemia. 774 61

The status of hemopoietic stem cell transplantation in Australia from January 1, 1993 to December 31, 1993 is reported. A total of 523 hematopoietic stem cell transplants were carried out throughout Australia during this 12 month period: 296 autologous transplants, 223 allogeneic transplants, and 4 syngeneic transplants. These were carried out by transplant programs in 20 hospitals, and the total number of transplants represented a 9.4% increase on the total number performed in 1992 (n = 478). Of the 296 autologous transplants, 133 utilized blood stem cells only, 125 marrow stem cells only, and 38 both. The most common indications for autologous transplant were non-Hodgkin's lymphoma (n = 92), acute myeloid leukemia (n = 53), breast cancer (n = 37), Hodgkin's disease (n = 33), and myeloma (n = 25). The most common indication for allogeneic transplantation was chronic myeloid leukemia (n = 59), acute myeloid leukemia (n = 56), acute lymphoblastic leukemia (n = 43), and severe aplastic anaemia (n = 14). The number of allogenic transplants performed for individual diseases was comparable between 1992 and 1993, but increases in the number of autologous transplants for non-Hodgkin's lymphoma (26%), Hodgkin's disease (45%), breast cancer (48%), and myeloma (20%) were seen.
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PMID:Hematopoietic stem cell transplantation in Australia in 1993. 775

Between 1981 and 1985, 1124 patients with histopathologically confirmed malignant disease were registered at the sole oncology clinic of Libya, 664 (59%) were males and 460 (41%) were females. Overall, malignant lymphoma (ML) was the most common cancer (180/1124, 16%), with non-Hodgkin's lymphoma (NHL) being more common (57.2%) than Hodgkin's disease (HD) (42.8%). Considered separately, lung cancer was the most common tumour (22.4%) in males with a male to female ratio among the highest in the world (18.6:1), 85% of our male patients were smokers and more than 50% had been smoking heavily for 20 years or more. Breast cancer was the most frequent tumour (29.8%) of females and the majority of our patients were of a younger age group (72.3% below 50 years). Almost all our patients were multiparous and had breast-fed their babies. Cancer of the cervix uteri was less frequent (4.5%) than ovarian cancer (7.8%). The incidence of colorectal cancer was higher (4.6%) than other African countries. Contrarily the primary tumours of liver (1.9%) and bladder (0.5%) were less frequent. Among the children, aged less than 10 years, the common solid tumours of childhood occurred in the following frequency, ML 31.2%, nervous system 19.2%, Wilm's tumour 16.8% and bone tumours 9.6%.
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PMID:Cancer in Libya--a retrospective study (1981-1985). 783 77


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