Clinical and prognostic features of advanced ovarian carcinoma.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
B Lund
Publications and source records attributed to B Lund.
Advanced ovarian cancer. Dose intensity.
BACKGROUND: The rationale for dose intensity is based on pre-clinical observations in experimental model systems of cancer as well as upon retrospective studies correlating the impact of dose intensity upon response rates and survival. MATERIALS AND METHODS: A review has been performed based on trials attempting to compare the effects of two different dose intensities of either cisplatin or carboplatin, combinations of cisplatin and carboplatin, combined platinum with additional agents, and high-dose chemotherapy, regimens requiring hematologic support. RESULTS: The early phase II trials suggested that there may be an important dose response range over clinically achievable platinum doses, but randomized trials have failed to consistently show a clinically significant improvement with high-dose therapy. Reasons for this may be differences in patient selection, that total dose is the most important factor, or that a more than two-fold increase in dose intensity is needed to detect differences in response and survival rates. Phase I and II studies indicate that high, but short lasting, response rates can be achieved with high-dose therapy with haematopoietic support in refractory patients, but the toxicity is substantial. Paclitaxel dose intensity is presently being studied in several trials. CONCLUSIONS: Future trials of dose intensity should be focused upon patients with small volume disease and drug sensitive tumours.
Antineoplastic Combined Chemotherapy Protocols↗
[Patient information--fear, hope and education. Interview by Kirsten Bjørnsson].
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Fear↗
Bone minerals and levothyroxine.
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Bone Density↗
Measurement of bone cell metabolism in vitro using mass spectrometry.
The metabolism of bone cells can be monitored directly and continuously 'in vitro' by a new technique, based on mass spectrometry. The consumption of oxygen and production of carbon dioxide were measured in 6 different cultures of human bone cells. The method was feasible for measurement of bone cell metabolism and was also tested in suspensions of hepatocytes. The data obtained with these cells were comparable to results obtained with traditional techniques, and a relation to cellular concentration was demonstrated.
Bone and Bones↗
The use of post-embedding immunoelectron microscopy in the diagnosis of glomerular diseases. Comparison of immunoelectron microscopic and immunofluorescence studies.
Fifty renal biopsies were studied by immunoelectron microscopy after embedding in a partly hydrophilic polyacrylic resin (LR White). Immunofluorescence studies were carried out on frozen sections of parallel tissue samples. Polyacrylic embedding gave good preservation of the renal ultrastructure and precise localization of immunoglobulin and C3c antibodies within glomerular electron-dense deposits. Non-specific staining of plasma proteins within vascular lumina could easily be detected. There was good correlation between immunoelectron and immunofluorescence microscopy. Immunoelectron microscopy is a very sensitive method, which can detect small amounts of antigen. More cases were, however, positive by immunofluorescence than by immunoelectron microscopy. This discrepancy may be explained by difference in sample size, and by difference in resolution of morphological details (electron microscopy versus fluorescence microscopy).
Acrylic Resins↗
CA-125, placental alkaline phosphatase and tissue polypeptide antigen as preoperative serum markers in ovarian carcinoma.
Blood samples were drawn before laparotomy in 42 cases of benign, 17 cases of borderline, and 53 cases of malignant epithelial ovarian neoplasms. The concentrations of CA-125, tissue polypeptide antigen, and placental alkaline phosphatase (PLAP) were determined. No significant difference was found between the levels of CA-125 and TPA. No significant correlation was seen between tumour type and these two markers; however, both were significantly correlated to tumour malignancy and clinical stage, and CA-125 was also correlated to tumour grade. No correlation was found between PLAP and the other markers or any of the above-mentioned parameters. If at least one of two or three markers was requested to be positive, a moderate increase in the 'detection rate' of malignant tumours was found. However, the rate of positive benign samples increased to as much as 41%. Requesting at least two markers out of two or three to be positive certainly reduced the number of 'false-positive' benign tumours, but the sensitivity for malignant tumours was reduced concomitantly to levels where marker determinations would be of little use. The study demonstrated a possible, but limited role for preoperative determinations of the markers. A combination of two or three markers was not superior to single markers. The results indicate that neither of these markers will be of significant value in a screening context.
Adenocarcinoma, Mucinous↗
Combination therapy with carboplatin/cisplatin/ifosfamide/etoposide in ovarian cancer.
In 1987 a phase II study of combined high-dose platinum (carboplatin 300/mg/m2 day 1, cisplatin 50 mg/m2 days 2 and 3 q4wk) was carried out in 42 previously untreated ovarian cancer patients with residual disease. Since then, another phase II study of combined high-dose platinum and ifosfamide (1,500 mg/m2 days 1 to 3) has been carried out in 37 patients, while a third study of combined high-dose platinum and etoposide (70 mg/m2 intravenously days 1 to 5) is ongoing. Pathologic complete response (CR) and partial response (PR) rates in the first two studies were 62% in 37 evaluable patients, and 58% in 36 patients, 22% and 42% of whom were CRs, respectively. The preliminary results from the third study were: CR plus PR, 56%; CR, 24%. Hematologic toxicity was the dose-limiting factor in all three studies. Myelosuppression became substantial, but manageable, if another drug was added to the platinum combination. The percentage of patients experiencing World Health Organization grades 3 and 4 toxicity during treatment were: white blood cells 44%, 92%, and 79%; platelets 81%, 100%, and 95%, respectively, in studies I, II, and III. Nonhematologic toxicity was modest in all studies. Dose-limiting neurotoxicity occurred in 7%, 6%, and 5%; nephrotoxicity in 22%, 6%, and 11% of the patients. The percentage of patients receiving the stipulated doses of all study drugs in the sixth cycle was 31 in the first study compared with none in the second study. Combined high-dose platinum given either alone or in combination with ifosfamide or etoposide is highly active in ovarian carcinoma. However, further follow-up and a randomized trial are needed to establish the superiority of any one regimen.
Adult↗
Plasma ubiquinone, alpha-tocopherol and cholesterol in man.
Plasma ubiquinone, coenzyme Q10 or CoQ10 has been analyzed in plasma together with alpha-tocopherol and free cholesterol in healthy sedentary male subjects (SS), endurance trained male athletes (ET) and male patients with severe ischemic heart disease (IHD). Higher means were found in SS compared to both IHD and ET. Moreover, the ratios CoQ10 and alpha-tocopherol over free cholesterol were higher. In all groups significant relationships were found between the two products of the mevalonate pathway: CoQ10 and cholesterol (r ranged 0.66-0.86, p less than 0.01). The two lipophilic antioxidants, CoQ10 and alpha-tocopherol, were interrelated only in IHD (r = 0.86, p less than 0.001), borderline in SS (r = 0.51, p less than 0.05) but not in ET. It is assumed that plasma free cholesterol reflects the capacity to transport lipids and lipophilic compounds in blood. With metabolic stress and an elevated radical formation as in IHD and ET, the lower CoQ10 and alpha-tocopherol to cholesterol ratios mirror a subsequent toll on the scavenging potential. The difference in LDL levels between IHD and ET and the different storage capacity of CoQ10 and alpha-tocopherol might explain the tight coupling in IHD but not in ET. It is possible that the toll reflects both an intra- and extracellular radical quenching activity. The joint effect of the two lipophilic, extracellular antioxidants CoQ10 and alpha-tocopherol role in protecting e.g. LDL particles from peroxidation is suggested.
Cholesterol↗
The Skejby Bone Marrow Donor Registry.
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Blood Donors↗
Prognostic importance of flow cytometric immunophenotyping of 540 consecutive patients with B-cell chronic lymphocytic leukemia.
Blood mononuclear cells from 540 newly diagnosed, unselected patients with B-cell chronic lymphocytic leukemia (CLL) were examined by immunofluorescence flow cytometry for a panel of surface membrane markers, including IgM and IgD, the monoclonal antibodies anti-CD3, -5, -20, -21, -22, -FMC7, and, for the final 125 patients, anti-CD23. There were 503 CD5+ and 37 CD5- cases. In the CD5+ cases, the cells typically expressed IgM, IgD, CD20, CD21, CD22, and CD23. In univariate analysis, age, clinical stage, IgM-fluorescence intensity, CD23, and FMC7 had significant prognostic importance, with high IgM-fluorescence intensity, high FMC7, and low CD23 expression being associated with a short survival. There was no significant difference in survival between 351 cases expressing IgMD and 55 cases expressing IgM without IgD, or between kappa and lambda light chain monoclonal cases. CD20, CD21, and CD22 had no prognostic importance. In Cox multiple regression analyses, age, CD23, IgM-fluorescence intensity, and clinical stage (International Workshop System) had independent prognostic importance. Thus, besides clinical variables, CD23 and IgM intensity might be useful prognostic markers in the management of CD5+, B-cell CLL. The survival of CD5- patients was on the borderline of being significantly shorter than that of CD5+ patients. The majority of the CD5- cases were FMC7+, CD23-, had strong IgM fluorescence, and had splenomegaly.
Aged↗
Aberrations of chromosome 6 in 193 newly diagnosed untreated cases of chronic lymphocytic leukemia.
Aberrations of chromosome 6 were observed in 11 of 193 cases of chronic lymphocytic leukemia diagnosed January 1, 1984-November 1, 1988 and investigated cytogenetically within 30 days after diagnosis. The 6p was rearranged in 5 cases: 4 balanced and 1 unbalanced translocation. The 6q was involved in 6 cases: 4 deletions and 2 balanced translocations. Three of the del(6q) may be identical: del(6)(q13q27). In two cases there were no additional aberrations. Aberrations of chromosome 6 correlated significantly with an advanced clinical stage, diffuse pattern of bone marrow infiltration, and increased SmIgM-fluorescence intensity. All these factors are associated with poor prognosis. Although the number of cases with 6q aberrations is still too small and the observation period too short to show significant influence on survival, the presence of 6q aberrations at diagnosis may prove useful in delineating a subtype of chronic lymphocytic leukemia with poor prognosis.
Bone Marrow↗
Prognostic factors for overall survival in patients with advanced ovarian carcinoma.
Twenty-one pretreatment variables were investigated for prognostic influence on survival in 301 previously untreated patients with ovarian carcinoma, stage IIB-IV. Patients were randomized to sequential combination chemotherapy: cyclophosphamide, doxorubicin, 5-fluorouracil, followed by cisplatin and hexamethylmelamine, or to the 3-drug combination alternating with the 2-drug combination every other month. Median overall survivals were 25 and 22 months, respectively, P greater than 0.4. Based on the results from a Cox multivariate stepwise analysis a subset of independent significant prognostic factors was found to include: residual tumor size, performance status, alkaline phosphatase, number of metastases, histological differentiation grade and type. A prognostic index was calculated for each patient and three prognostic categories of patients were determined. The 3-yr survival rates for patients with low-, intermediate-, and high-risk scores were 62, 31, and 7%, respectively. Multivariate analysis thus contributes further information about the disease, and a knowledge of the distribution of such factors across different trials is important when comparing treatment outcome.
Antineoplastic Combined Chemotherapy Protocols↗
Efficacy of enprofylline in acute airway obstruction.
The efficacy and safety of different regimens of intravenously administered enprofylline, an anti-asthma xanthine, were evaluated in a randomized open study, including 155 patients with acute exacerbation of obstructive lung disease. The regimen 2.5 mg/kg i.v. over 10 min was canceled after seven patients had been included, due to two cases of hypotensive/vasovagal reactions. The regimens 2.0 mg/kg/20 min and 2.5 mg/kg/20 min were significantly more effective with regard to bronchodilation than 2.0 mg/kg/10 min (PEF increase +35%, +30% and +17% respectively). Nausea and headache were the most common side effects (16-33% and 23-33% of the patients respectively on different regimens) with the lowest frequency on 2.0 mg/kg/20 min. Four additional hypotensive reactions occurred; one on each 2.0 mg/kg regimen and two on 2.5 mg/kg/20 min. The regimen 2.0 mg/kg20 min was found to be the most favourable with regard to efficacy and side effects. Enprofylline i.v. was found to be an effective bronchodilating treatment of acute airway obstruction but the frequency of side effects has to be considered.
Acute Disease↗
Reproducibility of histopathological evaluation in epithelial ovarian carcinoma. Clinical implications.
An interobserver analysis of the reproducibility of malignancy grade and of histological type classified according to World Health Organization criteria was performed in 261 ovarian tumours, stages IIB to IV. All available slides per patient including metastatic tumours (16%) were reviewed independently by two pathologists. Overall observed agreement regarding type was 68%. The chance-corrected agreement expressed by the kappa coefficient was 0.55 (95% confidence interval 0.49-0.61). Overall observed agreement regarding grade was 41% compared with a kappa coefficient of 0.19 (95% confidence interval 0.12-0.26). Kappa coefficients, ranging from 0.18 to -1.00 for associations between type categories and from 0.20 to -0.32 for grade categories, indicated that any suggested pattern of association could be caused by chance occurrences. A more objective approach to histopathology is needed in ovarian carcinoma before its prognostic impact can be assessed.
Carcinoma↗
Muscle fibre types, ubiquinone content and exercise capacity in hypertension and effort angina.
The composition of skeletal muscle fibre expressed as a percentage of slow twitch (ST), type I or "red" and fast twitch (FT), type II or "white" were determined in patients with hypertension (HT) or with severe ischaemic heart disease (IHD) and compared to age matched controls. Similarly, exercise capacity expressed as the cycle intensity eliciting a blood lactate concentration corresponding to 2.0 mmol x 1-1 were compared with healthy controls. Both patient groups had a higher percentage of FT fibres with relatively lower exercise capacities than their controls. The exercise capacities were reduced even when the relationship of decreased capacity with the percentage of increased FT was considered. There was an increase IHD but not in HT in patients with fibre subgroup FTc, which most probably reflected fibre trauma. Both patient groups were low in the skeletal muscle mitochondrial electron carrier and unspecific antioxidant ubiquinone, coenzyme Q10 or CoQ10. Patients with IHD but not HT showed, however, a faster fall in the ratio CoQ10 over ST% the higher the percentage value of ST. The ratio reflects the antioxidant activity related to CoQ10 in the fibre hosting most of the oxidative metabolism. A low ratio indicates a risk of metabolic lesion and cell trauma. This could explain fibre plasticity and offer an alternative cause to heredity in elucidating in deviating muscle fibre composition in patients with HT and IHD.
Adult↗
Comparison of the predictive power of different prognostic indices for overall survival in patients with advanced ovarian carcinoma.
Validation of a 5-covariate prognostic index (PI5) (performance status, stage, residual tumor size, histological grade, and ascites) derived from a group of 268 Dutch patients with advanced ovarian carcinoma was performed in a similar study of 301 Danish patients. Analysis of survival suggested an alternative 4-covariate PI (performance status, residual tumor size, age, weight/body surface) for the latter group. As residual tumor size and performance status were common to both indices, the predictive power of this 2-covariate PI (PI2) was also assessed in the Danish study and, subsequently, validated in the Dutch patients. The PI5 defined 10 and 9% of the Dutch patients as low and high risk patients with 3-year survival rates of 80 and 8%, respectively. In the Danish study the PI5 classified 14% to be high risk patients with a 3-year survival rate of 18%. Only a few patients (3%) were classified as low risk, making comparisons irrelevant. The PI2 classified 33 and 26% of the Danish patients as having 3-year survival rates of 67 and 13%, respectively. The corresponding Dutch PI2 values were 41 and 15% of the patients with 3-year survival rates of 60 and 8%, respectively. Although the PI5 possessed a better validity in the Danish study than the PI2 in the Dutch study, the PI2 may be the best prognostic index available for general use.
Analysis of Variance↗
[Sarcoma treatment in Denmark].
Approximately 240 sarcomas are registered annually in Denmark. Of these, 5/6 are soft-tissue sarcomas while the remainder consist of various types of sarcomas of bone. Determination of the histogenetic type, the degree of aplasia and the anatomical spread of the primary tumour is decisive for optimal prognostic assessment and for planning of the primary local treatment. The surgical treatment is aimed at radical treatment and, where tumours in extremities are concerned, this frequently involves reconstruction with endoprostheses with the object of salvaging the limb. Irradiation is indicated in cases of soft-tissue sarcoma which are not amenable to radical operation and as palliative treatment. In cases of soft-tissue sarcoma, cytostatic therapy with adriamycin alone or combined with iphosphamide in metastasizing disease can result in response in 30-50% of the patients. On the other hand, the value of adjuvant treatment is not yet elucidated. In cases of osteogenic sarcoma, the data available at present suggest that prolongation of the survival rate may be obtained by means of intensive adjuvant cytostatic treatment, but the optimal regimen is not yet defined. In other situations, cytostatic therapy must be considered as experimental and not indicated outside the fields of controlled investigations. Optimal diagnosis and treatment of sarcoma requires extensive multidisciplinary contributions which should be centralized in the fewest possible centres. Intimate national and international cooperation is also essential.
Antineoplastic Agents↗