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Biomedical subjects

P Sevelda

Publications and source records attributed to P Sevelda.

At least 37 records · Page 2Linked to original sources
PubMed1998

Prediction of toxicity but not of clinical course by determining carboplatin exposure in patients with epithelial ovarian cancer treated with a combination of carboplatin and cisplatin.

We present the data from 105 patients with primary epithelial ovarian cancer, who received up to 6 cycles of carboplatin (300 mg/m2) and cisplatin (100 mg/m2) as one treatment arm of a prospective randomized trial. Values for first-course carboplatin area-under-the-curve (AUC) were determined retrospectively. WHO grade 3-4 thrombocytopenia was found in 10% of patients with low AUC (AUC <4 mg/ml x min), but in 44.6% of patients with high AUC (AUC 4 mg/ml x min) (chi-square p<0.0001). No single case of ototoxicity was found in the low AUC group but in 12% of patients in the high AUC group (chi-square p=0.003). Determination of carboplatin AUC may prevent ototoxicity and severe thrombocytopenia for the first cycle of combined treatment with carboplatin and cisplatin.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

[Therapy studies of the Austrian Breast Cancer Group (ABC)].

The Austrian Breast Cancer Group (ABC) consisting of more than 60 participating centers in Austria has randomized more than 5800 patients in 11 randomized trials since 1984. At present, roughly 30% of all patients with the diagnosis primary breast cancer are accrued in protocols throughout the country. Due to specific activities, the breast conservation rate raised from an initial 20% to more than 60% in the last years. Multicenter trials are not only the basis for progress in medicine but also tools for quality control and quality improvement.

Antineoplastic Agents, Hormonal↗
PubMed1997

Taxol as second-line treatment in patients with advanced ovarian cancer after platinum-based first-line chemotherapy.

Salvage chemotherapy in platin-resistant patients typically results in low response rates and short survival, therefore new active cytotoxic agents must be found. One of these agents is paclitaxel (Taxol), isolated from the bark of the western yew which acts as an antimicrotubule agent. In our study 28 patients were treated with Taxol, 20 of whom had platinum-resistant tumors. Taxol was administered at a starting dose of 175 mg/m2, infused over 3 hr every 21 days. A total of 145 courses of Taxol was infused. Dexamethasone, diphenhydramine, and ranitidine were given as premedication. The response rate was 25% (3 complete and 4 partial remissions), the median survival duration was 15 months. In contrast to other studies we found a lower response rate in patients resistant to platinum-based therapy: 15% (no complete, 3 partial remissions). The most common severe toxicity was leukopenia, with grade 3 toxicity occurring in 10% of the courses; no grade 4 leukopenia or neutropenia was noted. Neurologic toxicity was a clinically significant adverse effect, with 1% of patients experiencing grade 3, 9% experiencing grade 2, and 3% experiencing grade 1 toxicity. Other adverse effects were less frequent and less severe. We conclude that paclitaxel, which in a prospective randomized trial has been shown to be the most active treatment of advanced ovarian cancer, yields low response rates in platinum-resistant patients. Only a few of them profited from second-line treatment with Taxol. This could be a new aspect in the treatment of platinum-resistant ovarian cancer with Taxol.

Adult↗
PubMed1997

Erythropoietin treatment under polychemotherapy in patients with gynecologic malignancies: a prospective, randomized, double-blind placebo-controlled multicenter study.

In order to examine the influence of erythropoietin (rHuEPO) on serum hemoglobin levels, transfusion requirements, and quality of life in patients with gynecologic malignancies under polychemotherapy and chronic tumor anemia (hemoglobin <11 g/dl), we performed a prospective, randomized, double-blinded placebo-controlled clinical trial. Between October 1992 and October 1993, 35 patients from 5 gynecologic departments were entered into this trial. Inclusion criteria were hemoglobin level <11 g/dl, ferritin level >29 ng/ml, stool negative for occult blood, and life expectancy for more than 3 months. Patients received either 150 U/kg body wt rHuEPO (Erypo by Cilag-Janssen) sc three times a week for 12 weeks (n = 23) or a placebo (n = 12). If the hemoglobin levels of the 4th, 8th, or 12th week were >2 g/dl above the baseline value and/or >12 g/dl, the patient was classified as a responder. Patients who required blood transfusions (hemoglobin <8 g/dl, erythrocytes <3 x 10(6)/ml, or clinical symptoms of anemia) were classified as nonresponders. A nonvalidated quality of life questionnaire was completed by the patient at the beginning of the treatment and then every fourth week before receiving chemotherapy. In the rHuEPO group 56.6% of the patients responded to the treatment (chi2 = 10.79, P = 0.001) and only 5 patients (21.7%) required blood transfusions, whereas 8 of 12 patients in the placebo group (66.6%) had to be transfused (chi2 = 6.81, P = 0.009). Quality of life did not differ significantly between the rHuEPO group and the placebo group of patients. Within the rHuEPO group those patients that responded showed a significant increase in physical activity after response in comparison to the preresponsive phase (P = 0.02, paired t test). We therefore concluded that rHuEPO significantly increases serum hemoglobin levels and decreases transfusions requirements while maintaining quality of life in patients with gynecological malignancies who are undergoing polychemotherapy.

Adult↗
PubMed1997

[Survival prognosis in ovarian carcinoma Figo stages III and IV: 1980-1985 versus 1986-1993. A comparison of 2 treatment periods].

We examined the survival prognosis of 638 patients who had ovarian carcinoma Figo stages III and IV. We considered two separate time periods, 1980-1985 versus 1986-1993, including the size of the postoperative residual tumor, polychemotherapy with and without platinum, histological grading 1 versus 2 and 3, Figo stage III versus IV, and ascites present versus no ascites. Since 1986, 96% of the patients received platinum-containing polychemotherapy at a dosage of > or = 75 mg/m2, whereas between 1980 and 1985, only 76% of these patients received platinum-containing polychemotherapy at a dosage of 50 mg/m2, and 24% of the patients received polychemotherapy without platinum. The size of residual tumor masses and also the time period of treatment had an independent influence on survival prognosis. Patients treated from 1980 to 1985 had a relative risk to die which was 1.44 times higher than for the patients who were studied from 1986 to 1993.

Adult↗
PubMed1996

Adjuvant chemotherapy plus tamoxifen compared with tamoxifen alone for postmenopausal breast cancer: meta-analysis of quality-adjusted survival.

BACKGROUND: Adjuvant tamoxifen for early breast cancer provides an improvement in relapse-free (RFS) and overall survival (OS), especially for older women. We carried out a meta-analysis to find out whether the benefit of adding chemotherapy to tamoxifen outweighs its costs in terms of toxic effects for postmenopausal patients. METHODS: The meta-analysis of quality-adjusted survival was based on data from 3920 patients aged 50 years or older with node-positive breast cancer randomly assigned in nine trials that compared combination chemotherapy plus tamoxifen with tamoxifen alone. The nine trials were included in the worldwide overview conducted by the early breast cancer trialists' collaborative group (EBCTCG). The quality-adjusted time without symptoms or toxicity (Q-TWiST) method was used to provide treatment comparisons incorporating differences in quality of life associated with subjective toxic effects of treatment and symptoms of disease relapse. FINDINGS: Within 7 years of follow-up the modest benefit of increased RFS and OS for patients who received chemotherapy just balanced the costs in terms of acute toxic side-effects. Chemotherapy-treated patients gained an average of 5.4 months of RFS and 2 months of OS (neither statistically significant), but had to receive cytotoxic treatment for between 2 and 24 months to achieve these gains. No values of preference weights for time spent undergoing chemotherapy and time after relapse gave significantly more Q-TWiST with chemotherapy plus tamoxifen than with tamoxifen alone. INTERPRETATION: Within 7 years of follow-up, adjuvant chemoendocrine therapy did not provide more quality-adjusted survival time than tamoxifen alone for women aged 50 years or older with node-positive breast cancer. Better selection and administration of chemotherapy regimen, different scheduling of chemotherapy and tamoxifen, and appropriate use of patient and tumour characteristics may increase the therapeutic advantage of the combination.

Antineoplastic Agents, Hormonal↗
PubMed1996

Laparoscopic surgery in cases of ovarian malignancies: an Austria-wide survey.

The purpose of the study was to determine the frequency of discovering a malignant ovarian mass when laparoscopy is used to manage an adnexal mass. A countrywide survey was undertaken in Austria, comprising questions about ovarian malignancy detected or accidentally treated by laparoscopy. The response rate of 66.7% represented a total of 54,198 laparoscopies, 16,601 laparoscopic surgeries on adnexal masses, and 108 cases of ovarian tumors subsequently found to be malignant (96 well-documented). Twenty patients were treated with laparoscopy alone. In 22 cases, laparoscopy was followed by immediate laparotomy. A delayed laparotomy (3-1415 days) was performed in 54 cases. Staging revealed FIGO classifications from stages Ia to IV. The follow-up time ranges from 2 to 220 months. Four recurrences have been reported. Thirteen patients died of tumor progression. Laparoscopic surgery on ovarian malignancies is a rare situation (0.65% of all endoscopic surgeries on adnexal masses). In cases of malignancy, a laparotomy has to be performed to ensure optimal staging and treatment.

Adolescent↗
PubMed1996

-CA-125 antigen as a prognostic factor for survival in patients with epithelial ovarian carcinoma of FIGO stage I--preliminary results-.

The tumour marker CA 125 has proved useful in monitoring the course of disease and in indicating responsiveness to therapy in patients suffering from epithelial ovarian cancer. Due to its poor sensitivity, however, attempts to improve early detection by screening with this tumour marker have been unsuccessful to date. This study was performed to evaluate whether there was a relation between pre-operative CA 125 levels and the survival of patients with epithelial ovarian cancer FIGO stage I. If such a relation exists, CA 125 may be an effective variable in singling out those subsets of patients with stage I disease for whom adjuvant chemotherapy would bring an additional therapeutic benefit. Our results suggest CA 125 may be a significant prognostic factor. With a 5-year survival of 43%, marker-positive ovarian cancer carries a poor prognosis. Since the question as the whether follow-up treatment is required in this early, potentially curable stage of disease, is contingent upon numerous factors and since an individualised therapeutic regimen may lead to increased survival rates, the prognostic influence of CA 125 and its relationship to other prognostic factors should be evaluated by multivariate analysis.

Biomarkers, Tumor↗
PubMed1996

[Plasminogen activator inhibitor 1 and prognosis in breast carcinoma].

The proteolytic enzyme urokinase-type plasminogen activator (uPA) plays an important role in degrading extracellular matrix. This seems to be an important step in cancer invasion and metastasis. uPA antigen levels correlate significantly with disease recurrence and death in breast cancer. To build up tumour stroma in primary tumours as well as in metastases, inhibition of proteolytic activity is necessary. In this study we investigated the correlation of the Plasminogen Activator Inhibitor 1 (PAI-1), which is the specific inhibitor of uPA and which seems to be important for tumour formation, with prognosis in breast cancer. PAI-1 antigen levels were measured in cytosols of 268 primary breast cancers. In 205 cases we correlated the PAI-1 status (cut-off value: 1 ng/mg) with the clinical outcome. Furthermore we investigated PAI-1 antigen levels in 10 benign breast tumours and 33 metastases. PAI-1 levels were significantly higher in primary carcinomas (median value: 0.62 ng/mg, range: 0 to 30.7) than in benign tumours (median value: 0 ng/mg, range: 0 to 0.1) and metastases showed elevated levels (median value: 1.05 ng/mg, range: 0 to 7.8) in comparison to the primary tumours (Kruskal-Wallis test: p < 0.05). We found that the PAI-1 status correlated significantly with early disease recurrence (Mantel-Test p = 0.0069) and overall survival (Mantel-Test p = 0.0121). After a median follow-up of 32 months (range 2-58), 36% of patients with PAI-1 antigen levels > or = 1 ng/mg (n = 72) showed an early relapse and 24% died, whereas only 19% of patients with PAI-1 antigen levels < 1 ng/mg (n = 133) relapsed and 9% died within the study period. A multivariate analysis revealed that in our study population PAI-1 is not an independent prognostic factor. According to our findings PAI-1 seems to be involved in the formation of extracellular matrix in primary carcinomas and metastases and is related to poor prognosis in breast cancer.

Adult↗
PubMed1996

[Value of prognostic factors in early stage ovarian carcinoma].

Only 20-30% of all ovarian cancers are diagnosed in stage I. To achieve a correct pathohistological stage I disease a staginglaparotomy has to be performed. This surgery consists of a bilateral oophorectomy, salpingectomy and total abdominal hysterectomy, an omentectomy, peritoneal lavage, multiple biopsies of the peritoneum and a retroperitoneal lymph node dissection. The most important established prognostic factor for survival is the histologic grading. Well differentiated tumors do not get any further adjuvant treatment, but moderately well differentiated tumors or undifferentiated tumors are treated with adjuvant cytotoxic polychemotherapy. All other prognostic factors like FIGO staging, puncture of the tumor and/or rupture of the tumor and histologic subtypes do have just a minor relevance for survival prognosis. In addition to grading the following factors also seem to have an influence on further survival, according to the results of different study groups: tumor ploidy, dense adhesions of the tumor and preoperative tumor marker CA-125. New prognostic factors like her-2 neu, int-2, epidermal growth factor, insulin like growth factor, angiogenesis and proteases have to demonstrate their value for survival prognosis yet before they can be established in routine diagnosis.

Biomarkers, Tumor↗
PubMed1996

[Surgical therapy of ovarian carcinoma].

Aim of primary surgery in early stage ovarian cancer (FIGO I-IIA) is a complete removal of all visible tumors and an exact staging of intraabdominal and retroperitoneal tumor spread. Debulking of tumor as radical as possible is the aim of surgery in advanced stages of disease (FIGO IIb-IV). After 2 to 3 cycles of an active polychemotherapy interventional debulking surgery is performed with the intention to remove all existing tumors in those patients with postoperative residual tumor masses > 1 cm in diameter after first surgery. Second-look surgery is performed after 6 cycles of first line polychemotherapy either to confirm a clinical complete remission pathohistologically or to debulk persisting residual tumors. Secondary tumordebulking and its influence on survival as well as the diagnostic value of second-look surgery is discussed controversially, so today second-look is confined to clinical protocols. Cytoreduction of relapsing tumor masses seems to prolong survival in those patients with a relapse free interval of more than 12 months. This seems to be an attractive therapeutic alternative. For the future one can expect more selective operation strategies on the basis of new biologic prognosticators and new developments in minimal invasive operation techniques.

Chemotherapy, Adjuvant↗
PubMed1996

[After-care and palliative therapeutic measures in ovarian carcinoma].

In the palliative treatment of incurable cancer cytotoxic chemotherapy is frequently used. While prolongation of life may be a desired aim of treatment, this is only rarely achieved. Most studies concentrate on the assessment of tumor size as a index of response, but of more importance is the evaluation of symptom relief and the effects of treatment on quality of life. There is an urgent need of guidelines for palliative treatments and care, which are based on appropriate end points for assessing benefit to patients.

Aftercare↗
PubMed1995

Microvessel density and vessel invasion in lymph-node-negative breast cancer: effect on recurrence-free survival.

Microvessel density (MVD) and blood and lymphatic vessel invasion (BLVI) were investigated with regard to their influence on the disease-free survival (DFS) in node-negative breast cancer patients. Paraffin embedded microsections of 230 patients with T1,2 N0 breast cancer were immunohistochemically stained for factor VIII-related antigen. Every cluster consisting of more than highlighted endothelial cells was considered a countable microvessel. MVD was counted in 4 fields of 0.25 mm2 each. All MVD values are given as value for the sum of 4 fields of 0.25 mm2 each, that is, I mm2. BLVI was considered positive, when at least one tumor cell could be identified in a stained lumen. Out of 230 patients, 49 experienced local or distant recurrence and had a mean MVD of 72.4/mm2, whereas 181 patients who lived without recurrent disease had a mean MVD of 45.3/mm2. BLVI was negative in 6.2% of the cases with and in 93.8% of the cases without recurrent disease. BLVI was positive in 59.4% of the cases without and 40.6% of the cases with recurrent disease. MVD and BLVI remained the only significant prognostic factors of DFS in the Cox-Model. Tumor size, histological grade, and hormonal-receptor status were not prognostically relevant in the Cox-model. 10-year-DFS was 93.3% in BLVI-negative/MVD < or = 40/mm2 patients, 88.1% when MVD was high or BLVI was positive and 48.9% in BLVI positive/MVD < or = 40/mm2 patients. Our present data indicate that MVD and BLVI identify a very-low risk group among node-negative breast cancer patients, who will not benefit from systemic adjuvant therapy. MVD and BLVI should be used as stratification criteria in clinical trails on node-negative breast cancer patients.

Adult↗
PubMed1995

HER-2 amplification but not butyrylcholinesterase multability reflects aggressiveness of European-originated ovarian tumors.

Tumorigenic roles were variably suggested for HER-2 and INT-2 oncogene amplifications and the "atypical" aspartate to glycine mutability in the butyrylcholinesterase (BCHE) gene in ovarian adenocarcinomas. To examine this notion we searched for correlations between these three phenomena and ovarian tumor classification and aggressiveness, using quantitative polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), and direct PCR sequencing. Our findings revealed no alleles carrying the atypical BCHE mutability in 30 European-originated patients with ovarian tumors compared with 11% (2/18) such alleles in Israeli patients with malignant ovarian tumors. This apparently reflected population diversity rather than disease relationship. INT-2 amplification was observed in 14/94 (15%) of the European patients; however, there was no correlation between this phenomenon and clinicopathological indices in the corresponding patients. In contrast, in 94 tumor samples we found that 40% (38/94) of the cases had HER-2 amplification. Moreover, there was a highly significant correlation (P < 0.008) between the over fivefold HER-2 amplification and ovarian tumor severity. These findings demonstrate an informative value for HER-2 amplification tests in tumor DNA, but not for INT-2 amplification or BCHE mutability, for the assessment of treatment.

Base Sequence↗
PubMed1995

DNA amplification of HER-2/neu and INT-2 oncogenes in epithelial ovarian cancer.

OBJECTIVE: Oncogene alterations are thought to be prognostic indices in patients with breast cancer. The present study was carried out to investigate the amplification of the HER-2/neu and INT-2 oncogenes in ovarian cancer. METHODS: In a retrospective study of 196 patients with epithelial ovarian cancer, the amplification of the oncogenes HER-2/neu and INT-2 in the DNA of paraffin-embedded tumor cells was determined by quantitative PCR. The purpose of this study was to analyze whether the two oncogenes correlated with such predictive factors as FIGO stage, histological grade, ascites, postoperative residual tumor mass, hormone receptor content, and preoperative CA 125 serum levels. The effect of HER-2/neu and INT-2 amplification on patient survival was also studied. RESULTS: The only correlation found in this study was between INT-2 and preoperative CA 125 levels (P = 0.03). No correlations were demonstrable between HER-2/neu (log-rank test; P = 0.67) and INT-2 (log-rank test; P = 0.75) amplifications and overall survival. CONCLUSION: Unlike the established prognostic factors, neither HER-2/neu nor INT-2 appears to be predictive for survival in patients with ovarian cancer.

Adolescent↗