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  • Life and Medical Sciences  (2)
  • cyclophosphamide  (2)
  • 1
    ISSN: 1569-8041
    Keywords: breast cancer ; cardiotoxicity ; cyclophosphamide ; epirubicin ; high dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To prospectively evaluate the long term cardiac effects of high-dose epirubicin and cyclophosphamide given to women with early stage, poor prognosis breast cancer. Patients and methods: Women with stage 2 breast cancer and 10+ nodes or 4+ nodes and estrogen receptor negative tumor, or stage 3 breast cancer received three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 gm/m2 with peripheral blood progenitor cell and filgrastim support. Treatment was given every 28 days (n = 79) or 21 days (n = 20). Fifty patients received radiotherapy to the chest wall or breast, 25 of to the left side. Patients were assessed clinically regularly during chemotherapy and at least three times yearly after completion of treatment. Cardiac left ventricular ejection fraction (LVEF) was assessed by radionuclide scan before therapy, after each cycle of chemotherapy, three months and six months after completion of chemotherapy, and yearly thereafter until relapse. Results: Ninety-nine women were treated, and 92 completed all three cycles of chemotherapy. The median age was 43 years (range 24 to 60 years). All patients were included in this analysis. The median relapse-free survival was 39 months (11 to 68 months). There was a significant fall in LVEF during chemotherapy. In general, there was no further deterioration in cardiac function from the third month after cessation of treatment, however there was substantial variation between individuals. 35 patients had at least one LVEF measure less than normal (〈50%), but the LVEF returned to normal in 20 of these with further follow-up. Cardiac dysfunction was not increased in women who received radiotherapy and was not different between cohorts given chemotherapy every three or every four weeks. One patient died of acute myocardial necrosis following the third cycle of chemotherapy. Two patients developed clinical evidence of cardiac failure, and another had radiological signs but was asymptomatic. One woman died of progressive cardiac failure, one recovered clinically but also developed recurrent breast cancer, while the third recovered after commencement of medical therapy. Conclusions: During follow-up after high-dose epirubicin and cyclophosphamide as delivered in this study, the LVEF fell to below normal in approximately one third of patients. However, in over half of these patients the LVEF subsequently recovered to the normal range, and the incidence of clinically evident chronic cardiac failure was low. Further follow-up is required to assess the long- term safety. A randomized comparison with standard-dose anthracycline-based chemotherapy is needed to determine whether this regimen is associated with an increased risk of clinical cardiac toxicity.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1569-8041
    Keywords: cyclophosphamide ; dose-escalation ; epirubicin ; filgrastim ; G-CSF ; non-Hodgkin's lymphoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: To define a maximum tolerated dose (MTD) for the combination of epirubicin and cyclophosphamide with filgrastim (r-met-HuG-CSF) in patients with advanced solid tumors and non-Hodgkin's lymphoma (NHL). Patients and methods: Thirty-five patients with advanced solid tumors were enrolled in stages I and II. Twenty-one patients were treated in stage I in sequential cohorts of at least three patients at increasing dosage levels of cyclophosphamide and epirubicin, for up to six cycles every 21 days. At the completion of stage I, a MTD for epirubicin was established. Fourteen patients were treated in stage II, in cohorts of three or more. The epirubicin dose remained constant at the MTD dosage from stage I. Cyclophosphamide was further dose-escalated to establish its MTD. Twenty-one patients with previously untreated non-Hodgkin's lymphoma were treated in stage III with the MTD established in the prior stages. Results: The MTD in stage I was epirubicin 150 mg/m2 and cyclophosphamide 1500 mg/m2 with cumulative neutropenia as the dose-limiting toxicity (DLT). Cumulative thrombocytopenia prevented further dose-escalation of cyclophosphamide in stage II. The stage III regimen consisted of six, 21-day cycles of epirubicin 150 mg/m2, cyclophosphamide 1500 mg/m2, vincristine 2 mg, and prednisolone 100 mg for five days with filgrastim support. Nineteen of twenty-one patients (90%) completed six cycles of treatment, eight (38%) without dose reduction. Common toxicity criteria (CTC) grade 4 neutropenia (neutrophil nadir 〈0.5 × 109/l) was documented in 85 of 118 cycles (72%). Neutropenic fever was documented in 17 of 21 patients (81%) on at least one occasion. Severe thrombocytopenia (〈25 × 109/l) was seen in fourteen of 118 cycles (12%) and increased with cycle number. There was no significant non-hematological toxicity. Conclusion: Significant dose-escalation of epirubicin and cyclophosphamide was possible with filgrastim support. The MTD achieved was approximately double that of standard-dose therapy. This study forms the basis of an ongoing randomized study evaluating dose-intensification in intermediate grade NHL.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    American Journal of Anatomy 128 (1970), S. 137-145 
    ISSN: 0002-9106
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Significant sex and strain differences in correlation of bone, body and skeletal weights show significant localized effects of sex and strain and a combination of both. Individually they seem to lack biological meaning. However, when considered in relation to the ponderal correlations, of which they are a part, they fall into place at the distal ends of a graded linear correlation series, both within and between limbs; and similarly between mandible and sacrum, respectively, with each bone of both limbs. The pattern of these gradients reveals a linear decline in correlation of bones with distance (rule of neighborhood, Karl Pearson) in most cases, but the exceptions are such as can be related to the functions in which they cooperate. In this way they demonstrate at least two major unifying genetic influences. One associates sex and strain with locomotion and the other with the incipient upright investigative posture of the Lagomorphs (including the rabbit). The expected effect of sex on the pelvis is apparently not expressed by these ponderal measurements. The manner in which this correlation approach, based on well established genetic growth differences, converges with the phylogenetic and ontogenetic concepts of normal and abnormal growth of bone in limbs and cranio-facial development suggests that a combination of correlation and epigenetic analysis would be helpful in establishing a sound genetic background for the newer biomechanic, functional matrix and architectonic approaches.
    Additional Material: 3 Tab.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Hoboken, NJ [u.a.] : Wiley-Blackwell
    Journal of Orthopaedic Research 2 (1984), S. 161-168 
    ISSN: 0736-0266
    Keywords: Rabbit ; Spondylosis ; Calcified nucleus pulposus ; Intervertebral disc degeneration ; Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The spines of 35 rabbits (32 New Zealand white and 3 AC/J), ranging in age from 3 months to 8½ years, were investigated systematically for spontaneous degenerative changes. Three types of lesion were observed. (1) The nucleus pulposus underwent chondroid metaplasia throughout the length of the vertebral column by the age of 2 years. (2) Hydroxyapatite deposition was found in the nucleus pulposus in 12 of 20 animals examined roentgenographically. The lesion occurred principally in the distal thoracic segments and was first observed in 3-month-old rabbits. (3) Spondylosis occurred in each of four macerated spines from animals 〉24 months old. Portions of the spine spared by disc calcification were affected.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
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