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ABSTRACT: Mit dem Einsatz der „targeted therapy“ wird derzeit eine Optimierung der Systemtherapie des Ovarialkarzinoms angestrebt. Der
Beitrag gibt einen Überblick über derzeit verfügbare zielgerichtete Substanzen und Studienkonzepte beim Ovarialkarzinom sowie
über die bereits vorliegenden Ergebnisse zu einzelnen dieser Ansätze. Dabei ist der Fokus auf in Deutschland durchgeführte
oder laufende Studien gerichtet.
The application of targeted therapy for ovarian cancer is aimed at optimization of systemic therapy. The present paper gives
an overview of currently available targeting substances, research on targeted therapies and the results of trials on individual
targeting studies in ovarian cancer. Focus is placed on clinical trials with targeted therapies in Germany.
Der Gynäkologe 04/2012; 42(3):179-184.
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C K Lee,
R J Simes,
C Brown,
S Lord,
U Wagner,
M Plante,
I Vergote,
C Pisano,
G Parma, A Burges, [......],
T Högberg,
J Bentley,
L Angleitner-Boubenizek,
A Ferrero,
B Richter,
H Hirte,
V Gebski,
J Pfisterer,
E Pujade-Lauraine,
M Friedlander
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ABSTRACT: Patients with platinum-sensitive recurrent ovarian cancer are a heterogeneous group, and it is not possible to accurately predict the progression-free survival (PFS) in these patients. We developed and validated a nomogram to help improve prediction of PFS in patients treated with platinum-based chemotherapy.
The nomogram was developed in a training cohort (n=955) from the CALYPSO trial and validated in the AGO-OVAR 2.5 Study (n=340). The proportional-hazards model (nomogram) was based on pre-treatment characteristics.
The nomogram had a concordance index (C-index) of 0.645. Significant predictors were tumour size platinum-chemotherapy-free interval, CA-125, number of organ metastatic sites and white blood count. When the nomogram was applied without CA-125 (CA-125 was not available in validation cohort), the C-indices were 0.624 (training) and 0.594 (validation). When classification was based only on the platinum-chemotherapy-free interval, the indices were 0.571 (training) and 0.560 (validation). The calibration plot in the validation cohort based on four predictors (without CA-125) suggested good agreement between actual and nomogram-predicted 12-month PFS probabilities.
This nomogram, using five pre-treatment characteristics, improves prediction of PFS in patients with platinum-sensitive ovarian cancer having platinum-based chemotherapy. It will be useful for the design and stratification of patients in clinical trials and also for counselling patients.
British Journal of Cancer 09/2011; 105(8):1144-50. · 5.04 Impact Factor
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C. KUEMPER md,
A. BURGES md,
professor P. HILLEMANNS md phd,
S. MUELLER-EGLOFF md,
M. LENHARD md,
N. DITSCH md,
professor A. STRAUSS md phd,
C. KUEMPER, A. BURGES,
P. HILLEMANNS,
S. MUELLER‐EGLOFF,
M. LENHARD,
N. DITSCH,
A. STRAUSS
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ABSTRACT: KUEMPER C., BURGES A., HILLEMANNS P., MUELLER-EGLOFF S., LENHARD M., DITSCH N. & STRAUSS A. (2009) European Journal of Cancer Care Supraclavicular lymph node metastases of unknown origin: HPV-typing identifies the primary tumourCancers of unknown primary origin (CUP) account for 0.5–10% of all malignancies. CUP patients with metastases have a median survival of approximately 6 months, despite therapy. Identification of the primary tumour site may offer the opportunity of a specific and more efficient treatment. The case of a 45-year-old woman with supraclavicular lymph node metastases of a squamous cell CUP is reported. A staging laparoscopy with multiple biopsies and a loop diathermy excision of the cervix were performed. Human papillomavirus (HPV)-testing in the tissues revealed the tumour cells as metastases of an occult cervical cancer. Primary platin-based chemotherapy combined with paclitaxel leads to a complete apparative remission. Twelve months later, staging positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose in combination with computed tomography identified an isolated left renal lymph node metastasis. The patient received targeted radiation therapy, combined with cisplatin. To date, 19 months after diagnosis, she is doing well without any evidence of disease. The presented case report addresses the difficulties involving the identification of CUP. HPV-DNA is found in over 95% of cervical cancers. As the presented case illustrates, testing for this virus DNA in human tissues can be a useful diagnostic tool in patients with CUP where cervical cancer is the possible primary tumour.
European Journal of Cancer Care 10/2009; 18(6):606 - 611. · 1.17 Impact Factor
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ABSTRACT: Cancers of unknown primary origin (CUP) account for 0.5-10% of all malignancies. CUP patients with metastases have a median survival of approximately 6 months, despite therapy. Identification of the primary tumour site may offer the opportunity of a specific and more efficient treatment. The case of a 45-year-old woman with supraclavicular lymph node metastases of a squamous cell CUP is reported. A staging laparoscopy with multiple biopsies and a loop diathermy excision of the cervix were performed. Human papillomavirus (HPV)-testing in the tissues revealed the tumour cells as metastases of an occult cervical cancer. Primary platin-based chemotherapy combined with paclitaxel leads to a complete apparative remission. Twelve months later, staging positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose in combination with computed tomography identified an isolated left renal lymph node metastasis. The patient received targeted radiation therapy, combined with cisplatin. To date, 19 months after diagnosis, she is doing well without any evidence of disease. The presented case report addresses the difficulties involving the identification of CUP. HPV-DNA is found in over 95% of cervical cancers. As the presented case illustrates, testing for this virus DNA in human tissues can be a useful diagnostic tool in patients with CUP where cervical cancer is the possible primary tumour.
European Journal of Cancer Care 06/2009; 18(6):606-11. · 1.17 Impact Factor
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P Harter,
M Hahmann,
H J Lueck,
M Poelcher,
P Wimberger,
O Ortmann,
U Canzler,
B Richter,
U Wagner,
A Hasenburg, A Burges,
S Loibl,
W Meier,
J Huober,
D Fink,
W Schroeder,
K Muenstedt,
B Schmalfeldt,
G Emons,
A du Bois
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ABSTRACT: Almost all retrospective trials pointed out that a benefit of surgery for recurrent ovarian cancer may be limited to patients in whom a macroscopic complete resection could be achieved. Peritoneal carcinomatosis has been reported to be either a negative predictor for resectability or a negative prognostic factor, or both. The role of peritoneal carcinomatosis in a multicenter trial was investigated.
Exploratory analysis of the DESKTOP I trial (multicenter trial of patients undergoing surgery for recurrent ovarian cancer, 2000 to 2003).
A total of 125 patients (50%) who underwent surgery for recurrent ovarian cancer had peritoneal carcinomatosis. Univariate analyses showed worse overall survival for patients with peritoneal carcinomatosis compared with patients without carcinomatosis (P < .0001). Patients with and without peritoneal carcinomatosis had a complete resection rate of 26% and 74%, respectively (P < .0001). This corresponded with the observation that patients with complete resection had a better prognosis than those with minimal residual disease of 1 to 5 mm, which commonly reflects peritoneal carcinomatosis (P = .0002). However, patients who underwent complete resection, despite peritoneal carcinomatosis, had a 2-year survival rate of 77%, which was similar to the 2-year survival rate of patients with completely debulked disease who did not have peritoneal carcinomatosis (81%) (P = .96). Analysis of prognostic factors did not show any independent effect of peritoneal carcinomatosis on survival in patients who underwent complete resection.
Peritoneal carcinomatosis was a negative predictor for complete resection but had no effect on prognosis if complete resection could be achieved. Improving surgical skills might be one step to increase the proportion of patients who might benefit from surgery for recurrent disease.
Annals of Surgical Oncology 03/2009; 16(5):1324-30. · 4.17 Impact Factor
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ABSTRACT: To analyze the prognostic influence of patient characteristics, diagnostic markers or therapeutic procedures in women diagnosed with early ovarian cancer based on relapse and survival in long term follow-up.
All women diagnosed and treated for early ovarian cancer at our institution between 1992 and 2006 were included in this retrospective study. Patient characteristics, clinical data including operative procedure, serum markers, stage and histology at first diagnosis as well as follow-up data were analyzed with regard to survival times and relapse rates.
Altogether, 116 patients were included. Mean follow-up time was 7.0 +/- 3.3 years (range 2-14 years). Histology revealed a serous tumor in 64.7% (75/116), mucinous in 19.0% (22/116) and endometiroid tumors in 7.8% (9/116) of all cases. TNM classification was pT1a in 49.1% (57/116), pT1b in 6% (7/116), pT1c in 32.8% (38/116) and pT2a in 12.1% (14/116). Lymph node involvement (N1) was found in 3.4% of all patients. 17 deaths and 17 relapses (each 14.7%) were documented during follow-up time with a mean time to recurrence of 3.3 +/- 2.1 years (range 1-7 years). The general 1-, 2-, 5- and 10-year survival rates were 99, 95.7 and 88.9 and 81.0%, respectively. Patients with tumor stage pT1a and pT1b had a significantly better survival (P = 0.0003) and significantly lower risk of recurrence (P = 0.0138) compared to higher tumor stages. Moreover, patients who experienced recurrent disease or presented with ascites at primary diagnosis had a significantly worse overall survival (recurrence: hazard ratio 0.17, 95% confidence interval 0.0155-0.2182, P = 0.0001; ascites: HR 2.84, CI 1.1919-10.1131, P = 0.0225). The risk for recurrent disease was significantly elevated for patients with low grade (G3) tumors (P = 0.0330). Interestingly, there was neither a worse survival rate nor a higher relapse rate for patients with primary laparoscopic surgical access.
Patients with early ovarian cancer stage pT1c and pT2a or low grade tumor have to be monitored closely in oncologic follow-up as they bare a significant risk for disease recurrence. Ascites at primary diagnosis, pT1c or pT2a tumor stage or recurrent disease are associated with a poor survival even in early ovarian cancer.
Archives of Gynecology 01/2009; 280(1):71-7. · 0.91 Impact Factor
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A van Dalen,
J Favier,
E Hallensleben, A Burges,
P Stieber,
H W A de Bruijn,
D Fink,
A Ferrero,
P McGing,
A Harlozinska,
Ch Kainz,
J Markowska,
R Molina,
C Sturgeon,
A Bowman,
R Einarsson,
H Goike
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ABSTRACT: To evaluate the prognostic significance for overall survival rate for the marker combination TPS and CA125 in ovarian cancer patients after three chemotherapy courses during long-term clinical follow-up.
The overall survival of 212 (out of 213) ovarian cancer patients (FIGO Stages I-IV) was analyzed in a prospective multicenter study during a 10-year clinical follow-up by univariate and multivariate analysis.
In patients with ovarian cancer FIGO Stage I (34 patients) or FIGO Stage II (30 patients) disease, the univariate and multivariate analysis of the 10-year overall survival data showed that CA125 and TPS serum levels were not independent prognostic factors. In the FIGO Stage III group (112 patients), the 10-year overall survival was 15.2%; while in the FIGO Stage IV group (36 patients) a 10-year overall survival of 5.6% was seen. Here, the tumor markers CA125 and TPS levels were significant prognostic factors in both univariate and multivariate analysis (p < 0.0001). In a combined FIGO Stage III + FIGO Stage IV group (60 patients with optimal debulking surgery), multivariate analysis demonstrated that CA125 and TPS levels were independent prognostic factors. For patients in this combined FIGO Stage III + IV group having both markers below respective discrimination level, 35.3% survived for more than ten years, as opposed to patients having one marker above the discrimination level where the 10-year survival was reduced to 10% of the patients. For patients showing both markers above the respective discrimination level, none of the patients survived for the 10-year follow-up time.
In FIGO III and IV ovarian cancer patients, only patients with CA 125 and TPS markers below the discrimination level after three chemotherapy courses indicated a favorable prognosis. Patients with an elevated level of CA 125 or TPS or both markers after three chemotherapy courses showed unfavorable prognosis.
European journal of gynaecological oncology 01/2009; 30(6):609-15. · 0.47 Impact Factor
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ABSTRACT: To assess the predictive value of positron emission tomography computed tomography (PET-CT) imaging in comparison to AGO-scoring in patients planned for cytoreductive surgery in recurrent ovarian cancer.
33 patients who had received a PET-CT for suspicion of recurrent ovarian cancer between 12/2003 and 08/2007 were included in the retrospective analysis. Indication for PET-CT was based on blood tumor markers Ca 125 or Ca 72-4 and clinical symptoms. Scanning was performed on a Philips Gemini System covering the body from the neck to the thighs one hour after administration of 200MBq fluorodesoxyglucose. PET-CT, surgery and the patient records were reviewed to analyze the predictive value of PET-CT in comparison to an AGO-scoring system based on clinical parameters with regard to the prediction of full resectability of abdominal tumor spread.
The statistical analysis of this data showed a sensitivity of 73% (95% C.I., 39-94%) and specificity of 80% (95% C.I., 29-97%) for AGO-scoring with a positive predictive value of 89% and a negative predictive value of 57%. PET-CT achieved a sensitivity of 100% (95% C.I., 72-100%) and specificity of 60% (95% C.I. 15-94%), with a positive predictive value of 85% and negative predictive value of 100%. Further analysis of the data of operated patients with concordant PET-CT and AGO-score (12/16) showed a very good prediction of full resectability with a sensitivity of 100% (95% C.I., 63-100%), specificity of 75% (95% C.I., 20-96%), positive predictive value of 89% and negative predictive value of 100%.
PET-CT and the AGO-score offer good tools to determine patients for full resectability in recurrent ovarian cancer. PET-CT has a higher negative and the AGO score a higher positive predictive value, and the combination of both improves the diagnostic accuracy.
European Journal of Obstetrics & Gynecology and Reproductive Biology 08/2008; 140(2):263-8. · 1.97 Impact Factor
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ABSTRACT: A multicenter non-randomized phase II study was initiated to evaluate tolerability and efficacy of pegylated liposomal doxorubicin (PLD) in combination with carboplatin in gynecologic malignancies.
One hundred forty women with recurrent or advanced endometrial (n=31), cervical or vaginal cancer (n=31), uterine sarcomas (n=11), or recurrent platinum-sensitive ovarian cancer (n=67) received six courses of PLD 40 mg/m2 and carboplatin (AUC 6) every 28 days.
Hematological toxicities with NCI-CTC grade 3/4 were anemia in 8%, thrombocytopenia in 14%, neutropenia in 24%, and febrile neutropenia in 2% of 652 cycles. Grade 3/4 non-hematological toxicities included fatigue (14% of patients), pain (10%), dyspnea (9%), palmar-plantar erythrodysesthesia (7%), and nausea/vomiting (7%). Dose intensity reached 87.2% for PLD and 88.2% for carboplatin. Seventy-four percent of all non-progressive patients received at least 5 cycles. Overall response rates were (116 patients evaluable for response): ovarian cancer (n=54) 68%, endometrial cancer (n=27) 44%, uterine sarcomas (n=9) 33%, and cervical/vaginal cancer (n=26) 12%. Median progression-free survival was 11.6 months (95%CI 9.6-14.1) for ovarian cancer and 9.5 months (95%CI 6.6-12.6) for endometrial cancer. Median overall survival was 23.8 months (95%CI 19.0-30.2) and 21.4 months (95%CI 11.9-), respectively.
The combination of PLD and carboplatin was well tolerated and feasible in patients with gynecologic malignancies. Efficacy was low in cervical/vaginal cancer, but promising in patients with endometrial cancer. Efficacy was within the expected range in recurrent platinum-sensitive ovarian cancer and is currently under further investigation in a prospective randomized phase III trial comparing PLD/carboplatin with paclitaxel/carboplatin (CALYPSO-trial; AGO-OVAR 2.9).
Gynecologic Oncology 01/2008; 107(3):518-25. · 3.89 Impact Factor
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ABSTRACT: The aim of this investigation was to assess the extent of stress and demands in patients during preparation for general anesthesia for elective surgical procedures.
A total of 52 female patients scheduled for elective gynecological surgery under general anesthesia were included in this prospective study. The extent and time course of actual demands describing perceived emotional stress was assessed at close intervals using the German version of the Questionnaire for Actual Demands (KAB). Pre-operative and postoperative anxiety was assessed using part one of Spielberger's state-trait-anxiety inventory (STAI-X1). This was compared to hemodynamic (heart rate und blood pressure) and endocrinal stress parameters [cortisol concentration in serum and saliva, prolactin and dehydroepiandrosteronesulfate (DHEA-S) in serum]. Postoperatively, all patients were asked to rate the quality of care during preparation for general anesthesia.
The extent of patients' demands and stress during preparation for general anesthesia could be quantified by the short questionnaire for the actual demands (KAB). So-called objective stress parameters like hemodynamic and endocrinal data alone did not correlate with perceived stress. However, the subjective information correlated with the nature of the underlying diagnosis. The postoperative assessment of quality of care during preparation for general anesthesia did not correlate with the course of actual demands and stress.
In future studies assessing the perioperative management of patients and quality of care, standardized testing questionnaires should be preferred, instead of vegetative parameters alone, to reliably evaluate perioperative demands and stress in surgical patients.
Der Anaesthesist 07/2007; 56(6):562-70. · 0.99 Impact Factor
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ABSTRACT: HintergrundZiel dieser Untersuchung war die Evaluation von Beanspruchung und Stress im engen zeitlichen Verlauf whrend der Vorbereitung zur Allgemeinansthesie fr geplante operative Eingriffe.Patienten und MethodeIn einer prospektiven Untersuchung wurden bei 52Patientinnen, die fr einen operativen gynkologischen Eingriff in Allgemeinansthesie vorgesehen waren, hmodynamische (Herzfrequenz und Blutdruck) und endokrine Stressparameter [Kortisolkonzentration in Serum und Speichel sowie Prolaktin und Dehydroepiandrosteronsulfat (DHEA-S) im Serum] bestimmt. Das subjektive Stressempfinden wurde mit dem Kurzantwortbogen zur aktuellen Beanspruchung (KAB) innerhalb kurzer Retestintervalle perioperativ und mit dem ersten Teil des Spielberger-State-Trait-Angstinventars (STAI-X1) pr- und postoperativ beurteilt. Postoperativ wurden alle Patientinnen zur ihrem Urteil ber die periprozedurale Qualitt und ihren Gesamteindruck whrend der Narkosevorbereitung befragt.ErgebnisseDie subjektiv empfundene Beanspruchung whrend der Narkosevorbereitung und die properativ empfundene Angst lieen sich mit standardisierten Fragebgen einschtzen. Hierbei korrelierte die Selbstauskunft mit der Dignitt der Grunderkrankung. Dagegen lieen hmodynamische und endokrine Messparameter keine Rckschlsse auf das aktuelle Befinden zu. Das postoperative Patientenurteil korrelierte nicht mit dem Verlauf der Beanspruchung.SchlussfolgerungIn zuknftigen Untersuchungen zum perioperativen Patienten- und Qualittsmanagement sollten standardisierte Testbgen – anstelle von vegetativen Messparametern allein – zur Evaluation der subjektiven Beanspruchung und des Stressempfindens bei Patienten mit operativen Eingriffen eingesetzt werden.BackgroundThe aim of this investigation was to assess the extent of stress and demands in patients during preparation for general anesthesia for elective surgical procedures.Patients and methodsA total of 52 female patients scheduled for elective gynecological surgery under general anesthesia were included in this prospective study. The extent and time course of actual demands describing perceived emotional stress was assessed at close intervals using the German version of the Questionnaire for Actual Demands (KAB). Pre-operative and postoperative anxiety was assessed using part one of Spielbergers state-trait-anxiety inventory (STAI-X1). This was compared to hemodynamic (heart rate und blood pressure) and endocrinal stress parameters [cortisol concentration in serum and saliva, prolactin and dehydroepiandrosteronesulfate (DHEA-S) in serum]. Postoperatively, all patients were asked to rate the quality of care during preparation for general anesthesia.ResultsThe extent of patients demands and stress during preparation for general anesthesia could be quantified by the short questionnaire for the actual demands (KAB). So-called objective stress parameters like hemodynamic and endocrinal data alone did not correlate with perceived stress. However, the subjective information correlated with the nature of the underlying diagnosis. The postoperative assessment of quality of care during preparation for general anesthesia did not correlate with the course of actual demands and stress.ConclusionIn future studies assessing the perioperative management of patients and quality of care, standardized testing questionnaires should be preferred, instead of vegetative parameters alone, to reliably evaluate perioperative demands and stress in surgical patients.
Der Anaesthesist 05/2007; 56(6):562-570. · 0.99 Impact Factor
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B Schmalfeldt,
A du Bois, A Burges,
G Emons,
D Fink,
M Gropp,
A Hasenburg,
W Jäger,
R Kimmig,
M Kiechle, [......],
K Münstedt,
O Ortmann,
J Pfisterer,
B Richter,
I Runnebaum,
W Schröder,
J Sehouli,
B Tanner,
U Wagner,
J Weis
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ABSTRACT: Recommendations for diagnosis and treatment of malignant ovarian tumors with regard to the most recent data were worked out in a consensus process and valued by level of evidence (LoE) and grade of recommendation (GoR) of the Canadian Task Force for Preventive Health Care by the members of the Kommission Ovar der Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO) in June 2005. A short version of these guidelines is presented.
Zentralblatt für Gynäkologie 03/2006; 128(1):11-7.
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ABSTRACT: Single-agent platinum and single-agent pegylated liposomal doxorubicin (PLD) are both effective in the treatment of gynecologic malignancies. Based on evidence that combination platinum-containing regimens offer superior efficacy versus single-agent regimens, we conducted this study to determine the maximum tolerated dose (MTD) of PLD in combination with carboplatin.
In this phase I/II dose-finding study, six courses of PLD (20, 30, 40 or 50 mg/m2) and carboplatin (AUC 6) were administered every 28 days to women with advanced gynecologic malignancies. Three to six patients were treated at each dose level; an additional 12 patients were treated at the MTD.
PLD 40 mg/m2 was identified as the MTD when administered with carboplatin. Five of 18 patients experienced a dose-limiting toxicity at the MTD; two patients had grade 3/4 neutropenia, and one each had grade 3 emesis and grade 3 thrombocytopenia and thrombosis. No patient developed cardiotoxicity. In 11 patients evaluable for response, there were two complete responses, two partial responses and four patients with stable disease.
The MTD for PLD when administered in combination with carboplatin is 40 mg/m2. This regimen is well tolerated and offers promising activity in women with advanced gynecologic malignancies.
Annals of Oncology 02/2006; 17(1):93-6. · 6.43 Impact Factor
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ABSTRACT: Data on HER-2/neu overexpression, its correlation to prognosis and the success of treatment with Herceptin((R)) in ovarian carcinomas are scarce and contradictory. Therefore we assessed HER-2/neu expression and amplification in a large series of ovarian tumours by using tissue microarrays (TMAs).
Two TMAs containing 173 invasive carcinomas, 36 borderline tumours, 20 granulosa cell tumours, 14 carcinosarcomas, 11 benign cystadenoms and eight other pelvic tumours were constructed to assess HER-2/neu gene amplification by fluorescence in-situ hybridization (FISH) and immunohistochemistry. Immunohistochemistry was successful in 94.3%; 81.8% were HercepTest negative, 11.3% were scored as 1+, 4.1% as 2+ and 2.8% as 3+, including 3.1% of invasive carcinomas, 2.8% of borderline tumours and 7.7% of carcinosarcomas; 83.6% could be analysed successfully by FISH revealing no aberration in 75.8%, low amplification in 2.7% and high amplification in 3.7% of the cases. In 17.8% monosomy, trisomy, polysomy or deletion could be detected. All cases with high-level amplification had 2+ or 3+ scores on immunohistochemistry.
TMA is a feasible tool to study a large number of ovarian cases. Correlation between immunohistochemistry and FISH was excellent. HER-2/neu overexpression or gene amplification does not correlate with histological tumour type, stage, grade or prognosis.
Histopathology 02/2006; 48(2):149-56. · 3.08 Impact Factor
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ABSTRACT: Some retrospective analyses have suggested that participation in clinical trials is associated with better outcome. However, it is not clear to what extent selection bias contributes to this observation.
We evaluated the reasons for non-enrolment of ovarian cancer patients in clinical trials. All patients with ovarian cancer not enrolled in clinical studies and treated in 2001 in the participating centres were documented retrospectively and compared with patients enrolled in clinical trials at the same institutions during the same time period.
Two hundred and seventy-four patients with advanced ovarian cancer (FIGO stage IIB-IV) were included, of whom 139 (51%) and 135 (49%) patients were enrolled in this study and in prospective clinical trials, respectively. Ninety-four of 274 patients (34%) did not meet the inclusion criteria for clinical trials. Of 180 eligible patients, 28 (16%) refused participation and a further 17 patients (9%) were not recruited although they met the inclusion criteria. The non-study patients were older (66.7 versus 57.2 years; P <0.0001), underwent less radical surgery (hysterectomy, oophorectomy and omentectomy performed: 61.2% versus 80.7%; P = 0.001; rate of lymphadenectomy 30.9% versus 45.2%; P = 0.015) and more frequently had bulky residual disease (residual disease >2 cm: 36.2% versus 20%; P = 0.016). However, 62% of the non-study patients were treated with the same chemotherapy as in the standard arm of the respective clinical studies.
Study patients differ substantially from non-study patients, thus hampering generalisation of study results. Our results suggest that at least some inclusion criteria for clinical trials should be modified to increase study participation without compromising safety.
Annals of Oncology 11/2005; 16(11):1801-5. · 6.43 Impact Factor
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ABSTRACT: Neurotoxicity is a common side effect of platinum/taxane-based therapy of ovarian cancer. We performed a double-blind randomized placebo-controlled trial to evaluate the influence of the cytoprotectant amifostine on the neurotoxicity of first-line therapy of ovarian cancer with paclitaxel/carboplatin with or without epirubicin.
Of 72 patients randomized, 71 were treated with paclitaxel 175 mg/m2 and carboplatin AUC5 with or without epirubicin 60 mg/m2 (q21 x 6) and randomized for i.v. premedication with amifostine 740 mg/m2 or placebo. Assessment included a questionnaire, NCI-CTC, tendon reflex activity (TRA), two-point discrimination (2-PD), measurement of vibration perception threshold (VPT) and vibration disappearance threshold (VDT), and quality of life.
The majority of neurotoxicity criteria showed a significant impairment during therapy in both treatment arms. A significant protective effect of amifostine was observed for 2-PD, TRA, VPT and VDT. Amifostine failed to improve the 'global health status quality of life' score significantly. Toxicities according to NCI-CTC showed improved sensory neuropathy (P = 0.0046) but a worsening in terms of nausea (P = 0.0005) and vomiting (P = 0.0083). No significant differences were observed for single sensory and motor symptoms, except for a better skilfulness in the amifostine group (P = 0.0404).
Amifostine improved sensory neuropathy according to NCI-CTC and with regard to objective neurological assessment, but there were almost no differences in self-estimated specific sensory or motor symptoms. Disadvantages with regard to non-neurological toxicities and inconsistent results for quality of life demand further evaluation of neuroprotection with amifostine as well as alternative approaches to prevent platinum-taxane induced neurotoxicity.
Supportive Care Cancer 11/2005; 13(10):797-805. · 2.60 Impact Factor
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J Pfisterer,
P Harter,
U Canzler,
B Richter,
C Jackisch,
M Hahmann,
A Hasenburg, A Burges,
S Loibl,
M Gropp,
J Huober,
D Fink,
A Bois
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ABSTRACT: The role of cytoreductive surgery (CS) in recurrent ovarian cancer (ROC) has not been clearly defined. We performed a retrospective study evaluating criteria for CS in ROC. Twenty-five institutions documented their patients with CS for invasive epithelial ROC performed 2000-2003. Two hundred sixty-seven patients were included. Complete tumor removal was achieved in 133 patients (50%). Complete resection was associated with prolonged survival compared to surgeries with residual tumor. Median survival of patients without residual tumor was 45.3 months and of patients with residual tumor, irrespective of its size, 19.0 months (HR 4.33; 95% CI 2.53-7.43; P < 0.0001). In a multivariate analysis, the following factors showed a significant influence on the probability to achieve a postoperative residual tumor of 0 mm: absence of ascites (<500 vs > or =500 mL: HR 4.63; 95% CI: 1.81-11.76; P= 0.0001), good performance status Eastern Cooperative Oncology Group (ECOG) 0 vs >0: HR: 2.41; 95% CI: 1.41-4.08; P= 0.001, and low FIGO stage at primary diagnosis (FIGO I/II vs III/IV: HR 1.87; 95% CI: 1.04-3.37; P= 0.036). Significant factors for survival after surgery for recurrence in a multivariate analysis were achievement of complete resection (residual tumor at surgery for recurrence 0 vs >0 mm: HR 2.86; 95% CI: 1.66-4.93; P < 0.001), absence of ascites (<500 vs > or =500 mL: HR 2.09; 95% CI: 1.18-3.71; P= 0.012), and application of a platinum-containing chemotherapy (platinum-containing chemotherapy vs others: HR 1.83; 95% CI: 1.16-2.88; P= 0.009). Only patients with complete resection seem to benefit from CS. This new panel of selection criteria will be evaluated in a prospective study.
International Journal of Gynecological Cancer 10/2005; 15 Suppl 3:195-8. · 1.65 Impact Factor
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A du Bois,
A Belau,
U Wagner,
J Pfisterer,
B Schmalfeldt,
B Richter,
A Staehle,
C Jackisch,
H J Lueck,
W Schroeder, A Burges,
S Olbricht,
G Elser
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ABSTRACT: A multicenter, nonrandomized, phase II study was initiated to evaluate the tolerability, toxicity, and activity of paclitaxel, carboplatin, and gemcitabine combination in previously untreated ovarian cancer.
Chemonaive patients who had radical debulking surgery for primary epithelial ovarian cancer International Federation of Gynecology and Obstetrics (FIGO) IC-IV received sequentially paclitaxel 175 mg/m(2), carboplatin AUC 5, and gemcitabine 800 mg/m(2) on day 1 and gemcitabine 800 mg/m(2) on day 8, every 3 weeks.
From October 2001 to July 2002, 55 patients were treated and evaluated. Main toxicities were hematological with NCI-CTC grade 3/4 anemia 12.7%, leukopenia 70.9%, neutropenia 76.3%, and thrombocytopenia 45.5. However, febrile neutropenia occurred only in 1.8%. Grade 3/4 nonhematological toxicities were rare and occurred in less than 10% of patients. Toxicity-induced treatment delays occurred in 3.1% of cycles and resulted in early treatment cessation in four patients. Dose intensity reached 90.8% for carboplatin and paclitaxel, and 73.3% for gemcitabine. Objective response was observed in 10 of 14 patients with measurable disease.
The triplet combination of paclitaxel-carboplatin-gemcitabine is feasible and active, with manageable hematological toxicity and no unexpected nonhematological toxicity. This regimen has proceeded to phase III evaluation.
Gynecologic Oncology 03/2005; 96(2):444-51. · 3.89 Impact Factor
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P Wimberger, A Burges,
V Gorbounova,
H Sommer,
B Schmalfeldt,
J Pfisterer,
M Lichinitser,
A Makhson,
M Ströhlein,
W Eiermann,
M Biakhov,
V Moiseenko,
Bois A du,
R Kimmig
Cancer Cell International. 01/2004;
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ABSTRACT: Uterine fibroids are the most common benign tumour affecting the female reproductive tract, 20% of all women older than 35 years are afflicted. Patients with fibroids tend to be asymptomatic, but fibroids may lead to meno-, metrorrhagia, hyper- and dysmenorrhoea and urination and defecation problems. If the fibroids do not cause any clinical symptoms and if there is no suspicion of a malignant tumor, there is no need for therapeutic intervention. Otherwise, besides the medical management with gestagenes and GnRH (gonadotropin-releasing hormone) analog, surgery represents the classical treatment. Hysterectomy is the common approach for women with completed family planning. For women who wish to conserve their fertility enucleation of the fibroids can be considered. These surgical procedures can be performed endoscopically or abdominally. Uterine artery embolisation, a radiological intervention, is less invasive and represents an interesting therapeutic alternative.
Der Radiologe 09/2003; 43(8):615-23. · 0.61 Impact Factor
