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P Sevelda

Publications and source records attributed to P Sevelda.

At least 19 recordsLinked to original sources
PubMed2006

Ifosfamide/mesna as salvage therapy in platinum pretreated ovarian cancer patients--long-term results of a phase II study.

PURPOSE: Salvage chemotherapy in advanced ovarian cancer is not yet standardized. PATIENTS: Twenty-one consecutive patients progressing on or relapsing after previous platinum-containing treatment were eligible for treatment with ifosfamide 5 g/m(2) infused over a 24-hour period every 3 weeks in a Phase II trial. After an initial bolus of 1 g/m(2) of mesna, mesna was applied at a dosage of 5 g/m(2) concomitantly with ifosfamide followed by additional dosages of 200 mg 3 times at 4-hour intervals after termination of the ifosfamide infusion. RESULTS: The rate of objective responses was 19 percent, with a 95%CI [5.45-41.91 percent]. One patient achieved a pathologic complete remission (pCR) and 3 patients a clinical partial remission (PR). Median time-to-progression was 3 months. One patient was a long-term survivor. Main toxicities according to NCI-CTC included Grade 4 neurotoxicity in one patient, Grade 3 gastrointestinal toxicity in 5 patients, Grade 3 infection in one patient, and Grade 3 and 4 leucopenia in 6 and 2 patients, respectively. CONCLUSIONS: Monotherapy with ifosfamide represents an active regimen for salvage chemotherapy in advanced ovarian cancer patients progressing on or relapsing after previous platinum-pretreatment, even yielding a long-term surivor.

Adenocarcinoma↗
PubMed2005

Phase I/II study of oral etoposide plus GM-CSF as second-line chemotherapy in platinum-pretreated patients with advanced ovarian cancer.

The aim of this phase I/II study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities of chronic oral etoposide given on days 1-10 followed by rescue with subcutaneous (s.c.) granulocyte-macrophage colony-stimulating factor (GM-CSF) on days 12-19 as second-line chemotherapy in platinum-pretreated patients (pts) with advanced ovarian carcinoma. Cohorts of three to six pts were treated with doses of oral etoposide from 750 mg m(-2) cycle(-1) escalated to 1250 mg m(-2) cycle(-1) over 10 days, every 3 weeks. Subcutaneous GM-CSF, 400 mug once daily, days 12-19, was added if dose-limiting granulocytopenia was encountered. In total, 18 pts with a median Karnofsky index of 80% (range, 70-100%) and a median time elapsed since the last platinum dose of 10 months (range, 1-24 months), 30% of whom showed visceral metastases, were treated at four dose levels (DLs) of oral etoposide on days 1-10 of each cycle as follows: DL 1, 750 mg m(-2) cycle(-1), without GM-CSF, three pts; DL 2, 1000 mg m(-2) cycle(-1), without GM-CSF, three pts; DL 3, 1000 mg m(-2) cycle(-1), with GM-CSF, six pts; and DL 4, 1250 mg m(-2) cycle(-1), with GM-CSF, six pts. All pts were assessable for toxicity and 16 pts for response. Dose-limiting toxicity (DLT) was reached at DL 4 by three of six pts, showing World Health Organization (WHO) toxicity grade 4. One patient died from gram-negative sepsis associated with granulocytopenia grade 4. Two more pts developed uncomplicated granulocytopenia grade 4. Thus, we recommend that DL 3 can be used for further phase II evaluation (i.e. oral etoposide 1000 mg m(-2) cycle(-1), days 1-10, followed by s.c. GM-CSF 400 mug, days 12-19). The clinical complete or partial responses in each patient cohort were: DL 1, one of three pts; DL 2, one of three pts; DL 3, three of five pts; and DL 4, two of five pts. In conclusion, in this phase I/II study, we defined the MTD and the dose recommended for the therapy with oral etoposide given over 10 days followed by s.c. GM-CSF in platinum-pretreated patients with advanced ovarian cancer. Our data demonstrate encouraging activity of this regimen and strongly support its further investigation in a phase II study.

Administration, Oral↗
PubMed2003

Lack of impact of platinum dose intensity on the outcome of ovarian cancer patients. 10-year results of a prospective randomised phase III study comparing carboplatin-cisplatin with cyclophosphamide-cisplatin.

This prospective multicentre phase III trial was conducted to assess whether increased platinum dose intensity (DI) by combining carboplatin with cisplatin has an impact on overall survival (OS) and progression-free interval (PFI) compared with the standard combination of cyclophosphamide and cisplatin in patients with epithelial ovarian cancer. A total of 253 patients with epithelial ovarian cancer of stages International Federation of Gynecology and Obstetrics (FIGO) IC-IV were randomised to receive either cyclophosphamide (600 mg/m(2), intravenously (i.v.), day 1) and cisplatin (100 mg/m(2), i.v., day 2) (n=125) as the standard regimen or carboplatin (300 mg/m(2), i.v., day 1) and cisplatin (100 mg/m(2), i.v., day 2) (n=128), every 28 days for six courses. The median follow-up was 6.0 years. 124 patients randomised to the platinum dose-intensified arm and 123 patients randomised to the standard arm met all of the eligibility criteria. Patient characteristics were well balanced between the two treatment groups. All eligible patients randomised were included in the analysis of OS and PFI. The median OS of the standard and platinum dose-intensified arms were 41.2 (95% Confidence Interval (CI): 29.2-50.7) and 43.0 months (95% CI: 34.3-63.2), respectively (P=Non-significant (N.S.). The median PFI in the standard arm was 29.7 (95% CI: 17.4-41.7) versus 23.1 months (95% CI: 17.8-35.4) in the platinum dose-intensified arm, respectively (P=N.S.). Toxicity, comprising leucopenia, granulocytopenia, thrombocytopenia, anaemia, emesis and nausea, was statistically significantly higher in the platinum dose-intensified arm than in the standard arm. Unexpectedly, no statistically significant differences were found between the 2 arms' overall neuro- and ototoxicity. When converting carboplatin-platinum into cisplatin-platinum on the basis of an equivalence ratio of 4:1, patients in the platinum dose-intensified arm received a total platinum dose 1.58 times the platinum dose of the standard arm. With 35.0 mg/m(2)/week being administered, the total platinum DI of the dose-intensified arm was statistically significantly (P<0.0001) higher than that of the standard regimen (with 22.0 mg/m(2) being administered). Calculating the average administered relative dose intensities of the regimens yielded almost identical results with 0.56 and 0.58 for the standard and experimental arms, respectively. Thus, by conventional means, a 1.6-fold increase in the platinum DI could be reached by combining carboplatin and cisplatin without unacceptable morbidity. Nevertheless, this did not translate into any therapeutic benefit for the patient, even in the optimally debulked group of patients for whom dose-intensification would have been expected to be of benefit.

Adult↗
PubMed2002

[Early experience with the advanced breast biopsy instrumentation system in a multicentre study].

Early Experience with the Advanced Breast Biopsy Instrumentation System in a Multicentre Study In an Austrian multicentre trial between September 1998 and December 2001, 474 procedures were performed with the Advanced Breast Biopsy Instrumentation (ABBI), and 389 were entered in the protocol. For reasons of patient comfort, radiological accuracy and low complication rate, the stereotactic excision biopsy with the ABBI system is a useful alternative to 'open' biopsy of non-palpable breast lesions, although there are technical limitations. The question of the therapeutic option in breast cancer cannot be answered yet.

Austria↗
PubMed2001

Prognostic importance of degree of differentiation and cyst rupture in stage I invasive epithelial ovarian carcinoma.

BACKGROUND: Previous studies on prognostic factors in stage I invasive epithelial ovarian carcinoma have been too small for robust conclusions to be reached. We undertook a retrospective study in a large international database to identify the most important prognostic variables. METHODS: 1545 patients with invasive epithelial ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] stage I) were included. The records of these patients were examined and data extracted for univariate and multivariate analysis of disease-free survival in relation to various clinical and pathological variables. FINDINGS: The multivariate analyses identified degree of differentiation as the most powerful prognostic indicator of disease-free survival (moderately vs well differentiated hazard ratio 3.13 [95% CI 1.68-5.85], poorly vs well differentiated 8.89 [4.96-15.9]), followed by rupture before surgery (2.65 [1.53-4.56]), rupture during surgery (1.64 [1.07-2.51]), FIGO 1973 stage Ib vs Ia 1.70 [1.01-2.85]) and age (per year 1.02 [1.00-1.03]). When the effects of these factors were accounted for, none of the following were of prognostic value: histological type, dense adhesions, extracapsular growth, ascites, FIGO stage 1988, and size of tumour. INTERPRETATION: Degree of differentiation, the most powerful prognostic indicator in stage I ovarian cancer, should be used in decisions on therapy in clinical practice and in the FIGO classification of stage I ovarian cancer. Rupture should be avoided during primary surgery of malignant ovarian tumours confined to the ovaries.

Cell Differentiation↗
PubMed2001

Prognostic influence of delays between exploratory and definitive laparotomy in the treatment of malignant ovarian tumors.

BACKGROUND: The aim of this retrospective study was to evaluate whether a delay between a preliminary exploratory laparotomy and a definitive staging laparotomy and interval chemotherapy between the two operations affected the prognosis of ovarian cancer. METHODS: Of 504 patients with malignant tumors of the ovary who were treated at the Department of Obstetrics and Gynecology between 1980 and 1993, there were 24 who had a delayed definitive staging laparotomy. RESULTS: Sixteen patients did not have chemotherapy between their two operations. After definitive laparotomy, 13 patients (54.2%) were free of disease and 11 patients had residual disease (45.8%). CONCLUSIONS: The value of chemotherapy between preliminary and definitive laparotomy in halting tumor growth was not demonstrated by the results of our analysis.

Adult↗
PubMed2001

Lunar phases and survival of breast cancer patients--a statistical analysis of 3,757 cases.

The potential influence of lunar phases on human life has been widely discussed by the lay press. The purpose of this study was to find out whether the timing of surgery during particular lunar phases influences the survival of breast cancer patients. It has been postulated that breast cancer surgery performed during the waxing moon, or particularly at full moon, is associated with a poorer outcome. We tested this hypothesis by evaluating the overall survival for 3,757 consecutive patients with invasive breast cancer. All patients underwent either modified radical mastectomy or breast conserving surgery plus radiotherapy, followed by adjuvant cytotoxic or hormonal therapy. The date of definitive surgery was allocated to the lunar phases. 1,904 (50.7%) patients were operated on during the waxing moon and 1,853 (47.3%) during the waning moon. The median follow-up was 74 months (range 1-372 months). The mean age at primary surgery did not differ significantly in the two groups 58.39 (SD 13.14) versus 58.34 (12.75) (p >0.05, t-test). Breast cancer stages at initial diagnosis were evenly distributed according to the lunar phases (p = 0.325; chi-square). Survival curves were plotted according to the method of Kaplan-Meier. No significant differences were observed when timing of surgery was allocated to the lunar phases (p = 0.4841, log-rank). Subgroup analysis of premenopausal patients revealed similar results (p = 0.2950, log-rank; n = 1072). Using multivariate Cox modelling, we found a significant association between the patient's age, stage of disease and survival, whereas no association with survival was observed for the timing of surgery (RR= 1.062; 95% CI, 0.970-1.163; p = 0.1937). No significant differences in overall survival of breast cancer patients were observed when timing of breast cancer surgery during the lunar cycle was considered. Although this was not a prospective randomized trial, the statistical magnitude of the results do not support any recommendations for scheduling patients for surgery at any particular day of the lunar phase.

Austria↗
PubMed2001

Impact of second look laparotomy and secondary cytoreductive surgery at second-look laparotomy in ovarian cancer patients.

OBJECTIVE: Currently, no prospective study supports or refutes the value of secondary cytoreductive surgery in patients with ovarian cancer. We therefore reviewed the surgical data of patients who underwent second-look laparotomy (SLL) with or without secondary cytoreductive surgery at our department. METHODS: Analysis is based on the data of 179 patients who had FIGO stage II (suboptimally staged), stage III or IV ovarian cancer, who received a platinum-based first-line chemotherapy, who were clinically considered to be tumor-free or had at least a clinically partial response to first-line chemotherapy, and who underwent SLL. In patients with macroscopic tumor the diagnostic SLL was followed by a secondary cytoreductive surgery in order to remove as much tumor as possible. Patients with a positive SLL were given second-line chemotherapy. Survival from SLL until death was considered the primary statistical endpoint. RESULTS: In 78 out of 179 (43.5%) a negative SLL could be confirmed pathologically. Patients with negative findings, with microscopic, and macroscopic disease at SLL had a median survival of 66.6, 57.2, and 19.0 months, respectively (p=0.0001). In patients who underwent a secondary cytoreductive operation and in whom residual tumor was none, less than 2 cm, or more than 2 cm, the median survival was 22.9, 17.8, and 15.5 months, respectively (p=0.325). CONCLUSIONS: The presence of macroscopic tumor at SLL is an adverse prognostic factor whereas the role of secondary cytoreductive surgery at SLL appears to be limited in the routine management of ovarian cancer patients.

Adult↗
PubMed1999

CA 125 regression after two completed cycles of chemotherapy: lack of prediction for long-term survival in patients with advanced ovarian cancer.

The prognostic influence of CA 125 regression between the time point before surgery and after two completed courses of chemotherapy was studied in 210 patients with advanced ovarian cancer, and was compared to other well established prognostic factors. CA 125 blood samples were collected preoperatively (CA 125 pre) and 3 months after surgery (CA 125 3 mo) (at the beginning of the 3rd cycle of chemotherapy). The parameter CA 125 regression defined as log10 (CA 125 3 mo/CA 125 pre) was used for statistical analysis. In a survival analysis using a Cox proportional hazards model, CA 125 regression (P = 0.0001), residual tumour (P = 0.0001), age (P = 0.0095) and grading (P = 0.044) were independent variables, whereas stage of disease, histology, ascites and type of surgery failed to retain significance. Using log10 (CA 125 3 mo/CA 125 pre) as simple covariate in a Cox model showed a hazard ratio of 1.70 (95% confidence interval 1.32-2.19, P = 0.0001). However, a detailed analysis of the interaction of time with the prognostic factor CA 125 regression on survival revealed a strong time-dependent effect with a hazard ratio of more than 6 immediately after two courses of chemotherapy, whereas within approximately 1 year the hazard ratio for the surviving patients dropped quickly to the neutral level of 1. In summary, CA 125 regression is an independent prognostic factor for survival of women with advanced ovarian cancer and allows an identification of a high-risk population among patients with advanced ovarian cancer. However, the discriminating power of serial CA 125 for long-term survival seems to be temporary and prediction of individual patients outcome is far less precise.

Adult↗
PubMed1998

The relationship of pretreatment serum hemoglobin level to the survival of epithelial ovarian carcinoma patients: a prospective review.

BACKGROUND: Tumor anemia is a common symptom in cancer patients. This study assessed the prognostic relationship of pretreatment serum hemoglobin levels to survival in a retrospective sample of 206 patients with epithelial ovarian carcinoma. METHODS: Survival analysis was evaluated by univariate (Kaplan-Meier product limit method and log rank test) and multivariate (Cox proportional hazards model) analysis. Mean values were compared by the Kruskal-Wallis test. Serum hemoglobin levels were determined in each patient 24-48 hours before surgery. Anemia was defined as a serum hemoglobin value below 12 g/dL. RESULTS: Tumor anemia was present in 32% of the patients before primary surgery. Hemoglobin levels were significantly lower in patients with residual tumor than in those with no detectable residual tumor after initial surgery (P = 0.008). Although statistically not significant, we found a trend toward lower hemoglobin levels with advanced stage of disease. For 5 years, overall survival probability was 38.5% and 52.3% for patients with pretreatment hemoglobin levels P = 0.008). In multivariate analysis, the relative risk of death was significantly associated with decreasing serum hemoglobin levels. No interaction was found between the grade of anemia and chemotherapy or radiation therapy with respect to its influence on overall survival. CONCLUSIONS: After adjustment for established prognostic factors, tumor anemia was found to have an independent relationship to the overall survival of patients with ovarian carcinoma. Because no significant interaction could be found between the grade of anemia and chemotherapy, marked tumor anemia was considered an indicator of the presence of biologically aggressive tumor cell clones.

Adult↗
PubMed1998

Unsuspected primary tubal carcinoma during operative laparoscopy.

OBJECTIVE: To evaluate the possible risk of dealing with an unsuspected primary carcinoma of the fallopian tube during laparoscopic surgery. METHODS: We performed a countrywide survey in Austria concerning laparoscopic procedures in cases of primary carcinoma of the tube. The questionnaire consisted of questions regarding the pre-, intra-, and postoperative management. RESULTS: Of 18,435 laparoscopies in cases of an adnexal mass, 5 cases were reported, when laparoscopy was performed on an unsuspected carcinoma of the tube. Therefore, the risk of detecting this malignancy during laparoscopy after preoperative evaluation is 1 in 3687 cases (0.028%). CONCLUSION: The risk of encountering an unsuspected primary carcinoma of the fallopian tube during laparoscopy in Austria is an extremely rare situation. In case of a malignancy, a staging or debulking laparotomy should be performed immediately or as soon as possible.

Aged↗
PubMed1998

Influence of delayed staging laparotomy after laparoscopic removal of ovarian masses later found malignant.

OBJECTIVE: To determine whether delayed laparotomy after attempted laparoscopic excision of an ovarian mass later found to be malignant has an impact on the stage of disease. METHODS: A questionnaire regarding laparoscopic management of ovarian masses later found to be malignant was mailed to all gynecologic departments in Austria. Of the 70 cases reported, laparotomy was performed after laparoscopy in 48 cases. In 24 of these cases, laparotomy was performed within 17 days of laparoscopy, whereas 24 cases involved a delay of more than 17 days. Twenty-two patients in whom laparotomy was performed immediately after laparoscopy were used as controls. RESULTS: In patients with borderline tumors who underwent laparotomy more than 17 days after laparoscopy, the odds ratio (OR) for International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IV disease was 5.3 (95% confidence interval [CI] 0.40, infinity), compared with patients undergoing immediate laparotomy (multivariate analysis). Patients with invasive ovarian cancer who underwent laparotomy more than 17 days after laparoscopy had an OR of 9.2 (CI 0.92, 481) for stage IIB-IV disease compared with patients undergoing immediate laparotomy (multivariate analysis). In patients with borderline tumors, multivariate analysis showed that the timing of laparotomy is an independent prognostic factor for the stage of disease. In invasive ovarian cancer, none of the factors evaluated by multivariate analysis was found to be an independent prognostic factor for the distribution of disease stage. A delay between laparoscopy and laparotomy may affect adversely the distribution of disease stage. CONCLUSION: The timing of subsequent laparotomy was found to be a factor predictive of the distribution of disease stage.

Adolescent↗
PubMed1998

Very low-dose adjuvant chemotherapy in steroid receptor negative stage I breast cancer patients. Austrian Breast Cancer Study Group.

A randomised clinical trial was performed to test whether or not low-dose chemotherapy lasting only 35 days improves the outcome of breast cancer patients with stage I disease and negative oestrogen and progesterone receptors (ER-, PgR-). Between 1984 and 1990, 277 stage I breast cancer patients with tumours negative for both oestrogen and progesterone receptors were randomised to receive either low-dose short-term chemotherapy or no chemotherapy. Chemotherapy consisted of one cycle of doxorubicin, vincristin (AV) and one cycle of cyclophosphamide, methotrexate, fluorouracil (CMF). Patients were stratified for tumour stage, type of surgery, menopausal status and participating centre. Results were analysed both by univariate and multivariate statistical. After a median length of follow-up of 84 months, disease-free (DFS) and overall survival (OS) did not differ significantly between patients having received adjuvant chemotherapy and the control group. Uni- and multivariate analysis did not show any significant prognostic or therapy related factor. A low-dose short-term adjuvant chemotherapy is insufficient to improve the prognosis of patients with breast cancer stage I with ER-, PgR-tumours.

Adult↗
PubMed1998

Color-coded and spectral Doppler flow in breast carcinomas--relationship with the tumor microvasculature.

The phenomenon of tumor angiogenesis is an important aspect of understanding tumor biology. Studies in breast carcinoma have shown microvessel density (MVD) assessed by immunohistochemistry to be of prognostic importance in primary breast cancer. On the other hand, recently developed highly sensitive color-coded Doppler techniques offer a noninvasive method to examine neovascularisation in breast tumors. The purpose of this study was to determine the relationship between Doppler flow parameters and microvessel count assessed by immunohistochemistry. Fifty-three patients with primary breast cancer were examined preoperatively with color-coded Doppler ultrasound. The obtained Doppler frequency spectra were analyzed for peak systolic flow velocity (Vmax). Following surgery, paraffin-embedded microsections were immunohistochemically stained for factor VIII-related antigen. Tumor angiogenesis was assessed by microvessel count under light microscopy. Undifferentiated tumors correlated with high MVD (p=0.009) whereas other clinicopathological parameters were not associated with MVD. Color Doppler signals were detected in 50 out of 53 breast tumors. Evaluation of tumor flow velocity with various clinicopathological parameters showed a significant correlation with tumor size (p=0.0001) and lymph node metastasis (p=0.02). However, there was no significant correlation between MVD and intratumoral blood flow velocity assessed by color-coded Doppler. Our findings showed that Doppler flow measurement did not correlate with the extent of tumor angiogenesis of breast cancer. The present data give circumstantial evidence that microvessel count assessed by immunohistochemistry reflects the microvascular network, whereas tumor vasculature documented by Doppler ultrasound supplies information on the macrovasculature.

Adult↗
PubMed1998

[Hormones and cancer: risk-benefit].

The influence which female sexual steroids, especially estrogen, have on the development of cancer has not only been shown epidemiologically, but also by experimental findings. Hormones, in spite of a known marginal increase in the risk of thrombosis and endometrial cancer, play an important role in the preventive cancer medication (oral contraceptives: ovarian and endometrial cancer; chemoprevention: high-risk breast cancer patients). Basically, hormone replacement therapy should be administered to all patients suffering from gynecological malignomas. In the case of patients suffering from breast cancer, the advantages of hormone replacement therapy (e.g., less risk of cardiovascular complications) need to be weighed against the disadvantages.

Contraceptives, Oral↗
PubMed1998

[Tamoxifen in the treatment of patients with breast cancer: results of the latest meta-analysis of prospective randomized clinical trials].

A meta-analysis of 55 prospective randomized clinical trials including more than 37,000 patients has analyzed the effectiveness of tamoxifen in the treatment of breast cancer. Standard treatment consists of 20 mg tamoxifen daily for 5 years in patients with either a positive estrogen receptor or a positive progesterone receptor status. This treatment achieves a 50% improvement of the 5-year relapse-free survival and a 28% improvement of the overall survival. Tamoxifen is effective in lymph node-negative and lymph node-positive patients as well as in premenopausal and postmenopausal women. The combination of chemotherapy with hormonal treatment is even more effective and brings a further improvement of survival of 50%. In addition, tamoxifen reduces the number of contralateral breast cancer cases to 50%, but increase the occurrence of endometrial cancers from 1.2/1,000 breast cancer patients within 10 years to 4.4/1,000 women. In conclusion, tamoxifen 20 mg daily for 5 years is the standard treatment of hormone receptor-positive breast cancer patients.

Antineoplastic Agents, Hormonal↗