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ABSTRACT: PURPOSE: The detection of disseminated tumor cells in the bone marrow (DTC-BM) of breast cancer patients is an independent prognostic factor. In recent years, the focus of research was on finding methods for the detection of circulating tumor cells (CTC) in peripheral blood (PB). In this study, we investigated the presence of DTC-BM and CTC by simultaneous examinations in 202 patients at different stages of the disease. METHODS: Immunocytochemical examination of DTC-BM (10-20 ml of BM) with the anti-cytokeratin (CK) antibody A45B/B3 followed a standardized protocol. Analysis of PB (7.5 ml) for the presence of CTC was performed with the CellSearch Analyzer system (Veridex, Raritan, NJ, USA). RESULTS: Overall, DTC-BM were detected in 57/202 (28.2 %, 1->1,000 DTC) and CTC in 41/202 (20.3 %, 1-411 CTC) patients. Congruence of findings was 71.3 % (144/202, p = .002). In 147 pts with primary diagnosis, congruence of results was 69.4 % (102/147). There was no significant correlation between DTC or CTC and the established pathological factors. After a median follow-up time of 34 months (0-82), presence of CTC was borderline significant for tumor-associated death (p = .060). For 41 patients at recurrence-free follow-up, congruence of results was 75.6 % (31/41, p = .018). In this group, there was a patient with both the highest DTC (>1,000) and CTC (411) count, and she presented with distant metastases 3 months later and had died 5 months after that. Of 14 patients with metastatic disease, 9 showed both DTC and CTC (overall congruence 78.6 %, p = .176). CONCLUSION: There was significant congruence between DTC and CTC, which even increased in patients at follow-up and in those with metastases. Repeated CTC examinations could be a valuable tool for monitoring patients or the effectiveness of therapies.
Journal of Cancer Research and Clinical Oncology 03/2013; · 2.56 Impact Factor
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ABSTRACT: Aim: We describe the impact of a sequential dose-dense schedule of carboplatin and paclitaxel on the quality of life (QoL) of patients with ovarian cancer.
In this multicenter phase II trial, four cycles of carboplatin followed by 12 cycles of weekly paclitaxel were applied after cytoreductive surgery. QoL was assessed using the QoL questionnaires EORTC QLQ-C30 and QLQ-OV28 before chemotherapy (baseline), after four cycles of carboplatin, at the end of treatment (EOT), and after 6, 12, and 24 months.
Out of 104 eligible patients 87 (84%) participated in at least one QoL assessment. At baseline, all QLQ-C30 scales and symptoms were significantly worse than age-adjusted values for the general population. Subsequently QoL improved in general. During chemotherapy with paclitaxel, most functioning scales and symptoms worsened slightly (not significantly). However, peripheral neuropathy and chemotherapy-related side-effects increased to clinically important levels. At the end of treatment, most QoL scores were similar to those of the general population, but physical functioning and fatigue were worse. Sexual functioning and peripheral neuropathy remained problematic.
QoL was affected mainly by the weekly paclitaxel schedule, but effects were in most cases only temporary. A dose-dense regimen using a sequential protocol may be favourable in terms of QoL.
Anticancer research 09/2012; 32(9):3969-76. · 1.73 Impact Factor
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Sven Mahner,
Gülten Oskay-Özcelik,
Elke Heidrich-Lorsbach,
Stefan Fuxius, Harald Sommer,
Peter Klare,
Antje Belau,
Birgit Ruhmland,
Thomas Heuser,
Heinz Kölbl,
Susanne Markmann,
Jalid Sehouli
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ABSTRACT: Treosulfan, an alkylating agent, has demonstrated activity in recurrent ovarian carcinoma. It is equieffective as oral (p.o.) and intravenous (i.v.) formulation. To explore the preference and compliance of elderly patients regarding p.o. or i.v. treosulfan for the treatment of relapsed ovarian carcinoma, women aged 65 years or older were included in this prospective multicenter study. Since elderly patients usually have several concomitant diseases and experience more treatment toxicity, an interim safety analysis was planned and performed after 25 patients finished therapy to assess the tolerability of the treatment regimens.
Patients had a free choice of treosulfan i.v. (7,000 mg/m(2) day 1 of a 28-day cycle) or p.o. (600 mg/m(2) day 1-28 of a 56-day cycle) for a maximum of 12 cycles (i.v.) or 12 months (p.o.). Indecisive patients were randomized. Toxicity was evaluated according to the NCI-CTC version 2.0.
Twenty-five of 51 recruited patients completed therapy at the time of the planned interim analysis (median age, 75 years; range, 70-82). Median ECOG was 1, and median number of prior chemotherapy regimens was 2. A median number of 4 cycles (range, 1-12) were administered per patient. Anemia was the most common hematological toxicity (88 % of patients). Most frequent non-hematological toxicities were nausea (76 %), constipation (68 %), and fatigue (64 %).
Treatment was generally well tolerated despite the fact that most patients suffered from multiple comorbidities and were heavily pretreated. There were no unexpected hematological or non-hematological toxicities. Based on this safety analysis, the next step of study recruitment was continued.
Journal of Cancer Research and Clinical Oncology 04/2012; 138(8):1413-9. · 2.56 Impact Factor
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Wolfgang Janni,
Florian D Vogl,
Gro Wiedswang,
Marit Synnestvedt,
Tanja Fehm,
Julia Jückstock,
Elin Borgen,
Brigitte Rack,
Stephan Braun, Harald Sommer,
Erich Solomayer,
Klaus Pantel,
Jahn Nesland,
Klaus Friese,
Bjørn Naume
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ABSTRACT: The prognostic significance of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients at the time of primary diagnosis has been confirmed by a large pooled analysis. In view of the lack of early indicators for secondary adjuvant treatment, we here evaluated whether the persistence of DTCs after adjuvant therapy increases the risk of subsequent relapse and death.
Individual patient data from 676 women with primary diagnosis of early breast cancer stages I-III from 3 follow-up studies were pooled. During clinical follow-up, patients underwent BM aspiration (BMA) to determine the presence of DTC. Tumor cells were detected by the standardized immunoassays. Univariate and multivariable proportional hazards models were estimated to assess the prognostic significance of DTC for disease-free survival (DFS) and overall survival (OS).
Patients were followed for a median of 89 months. BMA was performed at median 37 months after diagnosis of breast cancer. At follow-up BMA, 15.5% of patients had DTCs. The presence of DTC was an independent indicator of poor prognosis for DFS, distant DFS (DDFS), cancer-specific survival, and OS during the first 5 years following cancer diagnosis (log-rank test P < 0.001 values for all investigated endpoints).
Among breast cancer patients, persistent DTCs during follow-up significantly predicted the increased risk for subsequent relapse and death. Analysis of DTC might serve as a clinically useful monitoring tool and should be tested as an indicator for secondary adjuvant treatment intervention within clinical trials.
Clinical Cancer Research 03/2011; 17(9):2967-76. · 7.74 Impact Factor
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Hans-Joachim Stemmler,
Nadia Harbeck,
Isolde Gröll de Rivera,
Ursula Vehling Kaiser,
Gerhard Rauthe,
Wolfgang Abenhardt,
Almut Artmann, Harald Sommer,
Hans-Gerd Meerpohl,
Marion Kiechle,
Volker Heinemann
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ABSTRACT: Previous phase II studies have indicated a greatly reduced hematotoxicity of docetaxel-based regimens administered on weekly schedules. The present trial was initiated to randomly compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application.
Patients previously untreated with chemotherapy for metastatic disease were recruited. Patients aged >60 years or with a Karnofsky Perfomance Status (KPS) of 60-80% were eligible for the D2 study. Patients were randomized to receive docetaxel either on a 3-weekly [75 mg/m(2) every 3 weeks (q3w)] or on a weekly (30 mg/m(2) on days 1, 8, and 15; q4w) schedule. Treatment was continued until a maximum of 8 cycles, unacceptable toxicity, or disease progression. All patients received standard corticosteroid prophylaxis.
Since statistical significance for the primary endpoint (toxicity) was achieved in the interim analysis, the study was closed according to the study protocol (102 of 162 patients). Compared to the standard arm, leukopenia ≥grade 3 was a rare event in the weekly arm of the D2 study (per-patient analysis: 4.2% q1w vs. 51.9% q3w; p < 0.0001). No difference was observed between the 2 schedules regarding the occurrence of anemia or thrombocytopenia. With regard to nonhematological toxicity, there was a higher incidence of skin/nail and hepatological toxicity with the weekly schedule, whereas neurotoxicity was observed more often in the standard arm. The rate of omitted doses was significantly increased in the weekly arm (8.6% q1w vs. 0% q3w). The overall response rate was 22.9% in the weekly arm compared to 42.6% in the standard arm (p = 0.039). Time to progression was 5.4 (q1w) versus 6.3 (q3w) months (p = 0.91), and overall survival was 22.7 (q1w) versus 15.8 (q3w) months (p = 0.24).
The present data support the feasibility of both weekly and 3-weekly application of docetaxel. As expected, severe leukopenia seems avoidable in weekly scheduled single-agent docetaxel and may serve as an important treatment option, particularly in elderly patients and patients with a reduced performance status.
Oncology 03/2011; 79(3-4):197-203. · 2.27 Impact Factor
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Hans-Joachim Stemmler,
Nadia Harbeck,
Isolde Gröll de Rivera,
Ursula Vehling Kaiser,
Gerhard Rauthe,
Wolfgang Abenhardt,
Almut Artmann, Harald Sommer,
Hans-Gerd Meerpohl,
Marion Kiechle,
Volker Heinemann
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ABSTRACT: Previous phase II studies have indicated a greatly reduced hematotoxicity of docetaxel-based regimens administered on weekly schedules. The present trial was initiated to compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application in combination with doxorubicin.
Patients previously untreated with chemotherapy for metastatic disease were recruited. Inclusion criteria were age <65 years or a Karnofsky Performance Status of 70-100%. All patients in the D4 study received doxorubicin (50 mg/m(2)) on the first day of treatment in addition to docetaxel given either at a 3-weekly dose of 75 mg/m(2) every 3 weeks (q3w) or at a weekly dose of 35 mg/m(2) (days 1, 8, and 15; q4w). Treatment was continued until a maximum of 8 cycles, unacceptable toxicity, or disease progression. All patients received standard corticosteroid prophylaxis.
Since interim analysis showed failure to reach a significant difference for the primary endpoint (hematotoxicity, i.e. leukopenia), the study was closed according to the study protocol (85 of 242 patients). A lower-than-expected rate of leukopenia ≥ grade 3 was observed in the standard arm of the D4 study compared to the weekly schedule (per-patient analysis: 61.9% q3w vs. 65.1% q1w; p > 0.05). Grade 3 and grade 4 fever, diarrhea, and infections occurred more frequently in the standard arm, whereas neurotoxicity and skin/nail disorders were observed more frequently in the weekly arm. Except for fever, none of these differences reached a level of significance. Dose delays, dose reductions, and the rate of omitted doses were increased in the weekly arm. The overall response rate was 44.2% in the weekly arm compared to 52.4% in the standard arm (p = 0.52). Time to progression was 6.2 (q1w) versus 10.3 (q3w) months (p = 0.36), and overall survival was 20.5 (q1w) versus 28.7 (q3w) months (p = 0.98).
The present data support the feasibility of both weekly and 3-weekly application of docetaxel in combination with doxorubicin. Nevertheless, given that leukopenia was similar in both arms and the efficacy parameters were at least numerically inferior with the weekly schedule, standard 3-weekly application seems to be preferable for patients requiring combination chemotherapy.
Oncology 03/2011; 79(3-4):204-10. · 2.27 Impact Factor
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Jalid Sehouli,
Dirk Stengel,
Philipp Harter,
Christian Kurzeder,
Antje Belau,
Thomas Bogenrieder,
Susanne Markmann,
Sven Mahner,
Lothar Mueller,
Ralf Lorenz,
Andreas Nugent,
Jochen Wilke,
Andreas Kuznik,
Gabriele Doering,
Arthur Wischnik, Harald Sommer,
Hans-Gerd Meerpohl,
Willibald Schroeder,
Werner Lichtenegger,
Guelten Oskay-Oezcelik
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ABSTRACT: Weekly administration of topotecan (Tw) is less toxic and widely considered a better treatment option than conventional 5-day therapy (Tc) in women with platinum-resistant recurrent ovarian cancer. We conducted a randomized phase II trial (TOWER [Topotecan Weekly Versus Conventional 5-Day Schedule in Patients With Platinum-Resistant Ovarian Cancer]) to better define the ratio between benefits and risks with either treatment approach.
Patients were randomly assigned to two independent two-stage protocols of Tw (4 mg/m(2)/wk administered on days 1, 8, and 15) or Tc (1.25 mg/m(2)/d on days 1 to 5). We evaluated risk ratios (RRs) for the primary end point of clinical benefit (complete response, partial response, and stable disease), the duration of progression-free survival (PFS) and overall survival (OS), associated hazard ratios (HRs), and RRs of toxicity with 95% CIs.
In total, 194 patients were randomly assigned at 54 centers to Tw (n = 97) or Tc (n = 97). Clinical benefit was observed in 36 of 76 (47%; 95% CI, 36% to 59%) Tw and 46 of 80 (58%; 95% CI, 46% to 68%) Tc patients (RR, 1.21; 95% CI, 0.90 to 1.64; P = .205). Patients in the Tw group had a slightly shorter PFS (HR, 1.29; 95% CI, 0.96 to 1.76) but similar OS (HR, 1.04; 95% CI, 0.74 to 1.45) compared with Tc. Tw was associated with significantly lower risks of anemia (RR, 0.35; 95% CI, 0.16 to 0.79), neutropenia (RR, 0.38; 95% CI, 0.23 to 0.65), and thrombocytopenia (RR, 0.23; 95% CI, 0.09 to 0.57).
With regard to effectiveness in terms of response and PFS, Tc remains the standard of care in patients with platinum-resistant recurrent ovarian cancer. However, comparable OS rates and a favorable toxicity profile make Tw another viable treatment option in this setting.
Journal of Clinical Oncology 01/2011; 29(2):242-8. · 18.37 Impact Factor
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Brigitte Rack,
Christian Schindlbeck,
Julia Jückstock,
Eva-Maria Genss,
Philip Hepp,
Ralf Lorenz,
Hans Tesch,
Andreas Schneeweiss,
Matthias W Beckmann,
Werner Lichtenegger, Harald Sommer,
Klaus Friese,
Wolfgang Janni
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ABSTRACT: Several trials show that tumor markers at primary diagnosis of cancer have prognostic relevance and can predict dissemination of the disease. While MUC-1 markers are frequently used to monitor treatment efficacy in metastatic breast cancer, their role at primary diagnosis or during follow-up remains unclear. This translational research project within the SUCCESS trial evaluates the role of the tumor marker CA 27.29 before and after adjuvant chemotherapy, as well as after two and then five years in patients with early breast cancer.
The SUCCESS trial compared FEC (500/100/500)-docetaxel (100) vs. FEC (500/100/500)-docetaxel/gemcitabine (75/2000) and two vs. five years of zoledronate treatment in node-positive and high-risk node-negative patients with primary breast cancer. CA 27.29 was measured before chemotherapy in 2669 patients with the reagent ST AIA-PACK CA 27.29 for AIA-600II-Analyzer (Tosoh Bioscience, Belgium). Results of CA 27.29 above 31 U/ml were regarded as positive.
7.6% of patients had elevated marker levels after the completion of primary surgical treatment but before initiation of chemotherapy (n=202, mean 19, range 3-410 U/ml). No correlation between nodal status (p=0.55), grading (p=0.85), hormonal status (p=0.21), HER2/neu status on the primary tumor (p=0.58) and CA 27.29 was shown. However, larger tumor size (p=0.02), lobular histology (p<0.0001), older age (p<0.001) and postmenopausal hormone status before the start of treatment (p=0.006) were significantly associated with higher CA 27.29 levels.
These data indicate a close relationship between CA 27.29 and tumor mass persisting even several weeks after surgery, but also identify potential confounding factors that should be considered in interpreting tumor marker results. Further follow-up of the SUCCESS trial will clarify whether CA 27.29 measured after surgery but before the start of systemic treatment is prognostically relevant and whether it is a useful marker for treatment monitoring in the adjuvant setting.
Anticancer research 05/2010; 30(5):1837-41. · 1.73 Impact Factor
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Brigitte Rack,
Julia Jückstock,
Eva-Maria Genss,
Alexandra Schoberth,
Christian Schindlbeck,
Barbara Strobl,
Maja Heinrigs,
Gerhard Rammel,
Thomas Zwingers, Harald Sommer,
Klaus Friese,
Wolfgang Janni
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ABSTRACT: There is strong evidence for the isolated tumour cells (ITCs) in the bone marrow of breast cancer patients having prognostic impact both at primary diagnosis and during recurrence-free follow-up. The goal of this study was to investigate the therapeutic efficacy of zoledronate on the persistence of ITC.
A total of 172 primary breast cancer patients without evidence of distant recurrence but detection of ITC in bone marrow were followed up. Zoledronate was administered every 4 weeks for 6 months to 31 patients who had completed surgery and adjuvant chemotherapy. In a matched-pair analysis, these patients were compared to 141 patients who did not receive additional zoledronate treatment. The bone marrow was re-examined after a median of 7.9 months (SD 0.89) and 11.5 months (SD 12.41; p=0.11), respectively. Patients were followed-up prospectively for a median of 39 months after the first aspiration.
While ITCs were detected in all 172 patients at the time of first bone marrow aspiration, ITCs were detected in four patients (13%) following 6 months of zoledronate therapy in contrast to 38 patients (27%) of the control group (p=0.099). The reduction in cell numbers between the first and second aspiration reached statistical significance in the zoledronate group (p=0.02 vs. p=0.14). Persistent ITCs at the follow-up aspiration were associated with reduced recurrence-free survival (p=0.05).
These results indicate a potential antineoplastic effect of the cell cycle-independent agent zoledronate on persisting ITCs in a dormant state.
Anticancer research 05/2010; 30(5):1807-13. · 1.73 Impact Factor
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ABSTRACT: The number of long-term survivors of breast cancer has increased over recent decades because of many treatment advances. Thus, long-term quality of life (QoL) and factors affecting it are of growing research interest.
The authors investigated longitudinal changes in QoL and anxiety in breast cancer patients and differences in QoL and anxiety in various oncological subgroups.
A group of 236 women with a primary diagnosis of breast cancer or carcinoma in-situ completed questionnaires after surgical treatment, 6 months, and 12 months post-surgery.
QoL scores of breast cancer patients improved over time, but impairments in terms of anxiety, body image, and sexual functioning were still observed. Younger patients were more likely to be distressed by cancer diagnosis and treatment.
Surgical modality and tumor prognostic factors, however, seemed to play a minor role in patients' subjective QoL, which is discussed in terms of the "well-being paradox."
Psychosomatics 03/2010; 51(2):112-23. · 2.12 Impact Factor
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Brigitte Rack,
Ulrich Andergassen,
Julia Neugebauer,
Jessica Salmen,
Philip Hepp, Harald Sommer,
Werner Lichtenegger,
Klaus Friese,
Matthias W Beckmann,
Dagmar Hauner,
Hans Hauner,
Wolfgang Janni
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ABSTRACT: SUMMARY: Cohort trials have shown evidence that obesity and a low level of physical activity are not only associated with a higher risk of developing breast cancer, but also with an increased risk for recurrence and reduced survival in breast cancer patients. The SUCCESS C study is the first European trial to evaluate the effect of an intensive lifestyle intervention program on disease-free survival in women with early breast cancer and to examine the predictive value of selected biomarker candidates. A total of 3,547 women with early-stage, Her2/neu-negative breast cancer will be included. The first randomization will compare disease-free survival in patients treated with either 3 cycles of FEC (epirubicine, fluorouracil, cyclophosphamide), followed by 3 cycles of docetaxel or 6 cycles of docetaxel-cyclophosphamide, and thus assess the role of anthracycline-free chemotherapy. The second randomization compares disease-free survival in patients with a body mass index of 24-40 kg/m(2) receiving either a telephone-based individualized lifestyle intervention program aiming at moderate weight loss or general recommendations for a healthy lifestyle alone. In addition, the study will evaluate the predictive role of cancer-associated and obesity-related biomarkers for the prediction of disease recurrence and survival. This SUCCESS C trial will provide valuable information on the effects of a lifestyle intervention program on the prognosis of early breast cancer patients.
Breast Care 01/2010; 5(6):395-400. · 0.45 Impact Factor
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ABSTRACT: Loco-regional recurrences of the breast cancer are associated with a bad prognosis. Often costly autologous-tissue treatment as a surgery aiming at repairing the defects is necessary.
Four female patients were treated with the vacuum-assisted closure (VAC)-system in context with the recurrence resection. In all cases a primary local masking was not possible.
In the described cases the wounds healed well during the post-operative phase. There occurred no problems either during the radiation treatment or during chemotherapy in the case of lying VAC-Systems.
Using vacuum-assisted wound closure one can avoid autologous-tissue treatment in the case of extensive loco-regional recurrences.
Archives of Gynecology 11/2009; 281(5):927-32. · 0.91 Impact Factor
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Silke Steinbach,
Thomas Hummel,
Christina Böhner,
Sabina Berktold,
Walter Hundt,
Monika Kriner,
Petra Heinrich, Harald Sommer,
Claus Hanusch,
Anita Prechtl,
Burghart Schmidt,
Ingo Bauerfeind,
Katharina Seck,
Volker R Jacobs,
Barbara Schmalfeldt,
Nadia Harbeck
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ABSTRACT: Smell and taste changes during chemotherapy are significant complaints of cancer patients. Loss of olfactory/gustatory function can lead to malnutrition, weight loss, and possibly a prolonged morbidity of chemotherapy-induced adverse effects, decreased quality of life, poor compliance, and even decreased therapy response. This prospective study comprehensively investigated, to our knowledge for the first time, smell and taste changes in a cohort of 87 patients undergoing chemotherapy for breast cancer or gynecologic malignancies.
Olfactory function was tested using Sniffin' Sticks (Burghart; Wedel, Germany) and gustatory function was tested using taste strips before, during, and immediately and 3 months after chemotherapy.
Olfactory and gustatory function significantly decreased during chemotherapy and recovered almost completely 3 months after chemotherapy. Scores of odor thresholds were affected more than those of discrimination or identification. The olfactory function of older patients was affected more than that of younger patients. There was no difference in the olfactory function during chemotherapy with respect to the chemotherapeutic agent or initial diagnosis (breast or ovarian cancer). Regarding taste, scores of salty taste were affected more than scores of sweet, sour, or bitter taste. The gustatory function did not differ significantly during chemotherapy with respect to age or diagnosis but did differ with respect to the chemotherapeutic agent. Taxane-based chemotherapy caused the most severe disorders.
Chemotherapy has a significant but transient effect on olfactory and gustatory function, possibly causing reduced appetite, a low energy intake, and weight loss. Additional spices and flavoring may compensate for this diminished chemosensory function, enhancing patient compliance and quality of life.
Journal of Clinical Oncology 04/2009; 27(11):1899-905. · 18.37 Impact Factor
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Ioannis Mylonas,
Silvia Worbs,
Naim Shabani,
Christina Kuhn,
Susanne Kunze,
Sandra Schulze,
Darius Dian,
Andrea Gingelmaier,
Christian Schindlbeck,
Ansgar Brüning, Harald Sommer,
Udo Jeschke,
Klaus Friese
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ABSTRACT: Inhibins are dimeric glycoproteins, composed of an alpha-subunit (inhibin-alpha) and one of two possible beta-subunits (betaA or betaB), with substantial roles in human reproduction and in endocrine-responsive tumours. The aims of this study were to determine the distribution of inhibin-alpha, -betaA and -betaB subunits in malignant human endometrial tissue and the assessment of an association with specific clinicopathologic tumour features and clinical outcome. A series of 302 endometrial cancer tissue samples were immunohistochemically analysed with monoclonal antibodies against inhibin subunits. The inhibin-alpha subunit showed a significant association with histological grading, surgical staging, lymph node status and diabetes in patients with endometrial cancer. Interestingly, loss of inhibin-alpha expression resulted in a poorer survival of endometrial cancer patients. Additionally, survival analysis demonstrated that inhibin-alpha immunoreactivity was an independent prognostic factor for progression-free survival, cause-specific survival as well as for overall survival. In contrast, although inhibin-betaA- and -betaB subunits showed a significant association between endometrial histological subtypes and histological grading, both subunits were not found to be associated with survival in endometrial cancer patients. Therefore, inhibin-alpha immunostaining might be used as a simple and efficient marker to identify high-risk patients leading to the selection of patients for an aggressive adjuvant therapy.
European journal of cancer (Oxford, England: 1990) 03/2009; 45(7):1304-14. · 4.12 Impact Factor
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Gabriele Hölscher,
Christoph Anthuber,
Gunther Bastert,
Alexander Burges,
Doris Mayr,
Ernst Oberlechner,
Gabriele Schubert-Fritschle,
Sonja Sinz, Harald Sommer,
Barbara Schmalfeldt,
Jutta Engel
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ABSTRACT: To highlight aspects of malignant ovarian sex cord stromal tumors, effects of treatment, and developments over the past 28 years.
Population-based cohort study.
Gynecological departments within the catchment-area of the Munich Cancer Registry and associated with the project group 'Malignant Ovarian Tumors' of the Munich Cancer Center.
One hundred and forty-five women with an invasive single sex cord stromal tumor diagnosed between 1978 and 2005.
Overall survival was estimated with the Kaplan-Meier method, relative survival was computed by the ratio of observed to expected survival rate. The impact of age, International Federation of Gynecology and Obstetrics (FIGO)-stage, residual tumor, and chemotherapy was examined by multivariate analysis (Cox regression model).
Overall and relative survival and multivariate adjusted overall survival.
Survival data showed a five-/10-year overall survival of 55.8%/42.8% (relative survival 58.6%/49.2%) for women diagnosed before 1988 and 89.1%/78.3% (relative survival 92.7%/85.2%) for women diagnosed after 1988. After adjustment for age and FIGO-stage, the following hazard ratios and 95% confidence intervals (95% CI) for treatment methods resulted: 3.3 (95% CI 1.5-7.0) for women with compared to women without residual tumor and 2.2 (95% CI 1.2-4.2) for women with chemotherapy compared to women where no chemotherapy was given.
Improvements in survival may be attributed to a stage-shift toward more favorable stages at diagnosis and to advances in treatment such as improved surgery without residual tumor. There is no evidence for any benefit of adjuvant chemotherapy. Surgery remains the cornerstone of treatment, yet the benefit of postoperative therapy is still under debate.
Acta Obstetricia Et Gynecologica Scandinavica 03/2009; 88(4):440-8. · 1.77 Impact Factor
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ABSTRACT: The aim of this study was to investigate changes in the quality of life (QoL) and body image among breast cancer patients over 2 years and to examine different predictive factors for QoL 2 years after the primary operation.
A total of 203 women with a primary diagnosis of breast cancer completed the questionnaires 2 weeks and 6, 12, 18, and 24 months after surgery. Quality of Life Questionnaire (QLQ-C30), Breast Cancer Specific Quality of Life Questionnaire Module (QLQ-BR23), Questionnaire on Stress in Cancer Patients (QSC-R23), Freiburg Personality Inventory (FPI-R), Life Orientation Test (LOT) were used as standardized measures.
The overall QoL and most functional and symptom scales improved during the 2-year period. However, cognitive functioning, body image, and the three symptom scales of insomnia, constipation, and diarrhea did not change. Age was only capable of predicting physical functioning, whereas tumor size, axillary surgery, and adjuvant chemotherapy were not predictive of the long-term QoL functional scores. Initial distress was the most potent predictive factor for long-term QoL. Baseline functioning predicted functional QoL scores 2 years later. And higher scores for neuroticism were associated with a poorer QoL. However, optimism was not capable of predicting the QoL 2 years later.
Screening measures should be implemented at the time when breast cancer is diagnosed, in order to identify psychologically vulnerable patients and offer them professional psycho-oncological help.
Psycho-Oncology 02/2009; 19(2):160-9. · 3.34 Impact Factor
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Sibylle Loibl,
Gunter von Minckwitz,
Nadia Harbeck,
Wolfgang Janni,
Dirk Elling,
Manfred Kaufmann,
Holm Eggemann,
Valentina Nekljudova, Harald Sommer,
Marion Kiechle,
Sherko Kümmel
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ABSTRACT: Despite the fact that people older than 65 years of age have the highest incidence of developing breast cancer, these patients are excluded from clinical trials in most cases. Furthermore, most physicians tend towards therapy regimens without the use of dose-dense, highly active taxane-based treatments because of a lack of data regarding toxicities of these compounds in older patients.
Pooled side-effect data were analyzed from four prospective, randomized clinical trials in which patients of different age groups (< 60 years, between 60 and 64 years, and > 64 years) with primary breast cancer received taxane-based chemotherapy.
Dose delays, dose reductions, hospitalization, and therapy discontinuation increased with age. Hematologic toxicities and some nonhematologic toxicities were generally more common in older patients. Leucopenia increased from 55.3% in patients aged < 60 years to 65.5% in patients aged > 64 years (P < 0.001), and neutropenia increased from 46.9% to 57.4% (P < 0.001). There was no difference, however, in clinically more relevant febrile neutropenia between the different age groups. Thrombopenia shows a similar age-dependent increase, whereas there is no difference between the age groups concerning anemia. Hot flushes and elevated liver enzymes decreased with increasing age.
The present pooled analysis of a substantial cohort of older primary breast cancer patients demonstrates that taxane-containing (neo)adjuvant chemotherapy is feasible in older patients and that toxicity can be reduced by sequential therapy regimens.
Breast cancer research: BCR 10/2008; 10(5):R77. · 5.24 Impact Factor
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Jalid Sehouli,
Dirk Stengel,
Guelten Oskay-Oezcelik,
Alain G Zeimet, Harald Sommer,
Peter Klare,
Martina Stauch,
Axel Paulenz,
Oumar Camara,
Elke Keil,
Werner Lichtenegger
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ABSTRACT: The management of recurrent ovarian cancer remains controversial. Single-agent topotecan is an established treatment option, and preliminary evidence suggests improved tumor control by combining topotecan with etoposide or gemcitabine.
Women with relapsed ovarian cancer after primary surgery and platinum-based chemotherapy were randomly assigned to topotecan monotherapy 1.25 mg/m(2)/d, topotecan 1.0 mg/m(2) plus oral etoposide 50 mg/d, or topotecan 0.5 mg/m(2)/d plus gemcitabine 800 mg/m(2) on day 1 and 600 mg/m(2) on day 8 every 3 weeks. Patients were stratified for platinum-refractory and platinum-sensitive disease according to a recurrence-free interval of less or more than 12 months, respectively. The primary end point was overall survival. Secondary end points included progression-free survival, objective response rates, toxicity, and quality of life (as measured by the European Organisation for Research and Treatment of Cancer [EORTC] 30-item Quality-of-Life Questionnaire).
The trial enrolled 502 patients with a mean age of 60.5 years (+/- 10.2 years), 208 of whom were platinum resistant. Median overall survival was 17.2 months (95% CI, 13.5 to 21.9 months) with topotecan, 17.8 months (95% CI, 13.7 to 20.0 months) with topotecan plus etoposide (log-rank P = .7647), and 15.2 months (95% CI, 11.3 to 20.9 months) with topotecan plus gemcitabine (log-rank P = .2344). Platinum-sensitive patients lived significantly longer than platinum-refractory patients (21.9 v 10.6 months). The median progression-free survival was 7.0, 7.8, and 6.3 months, respectively. Objective response rates were 27.8%, 36.1%, and 31.6%, respectively. Patients under combined treatment were at higher risk of severe thrombocytopenia.
Nonplatinum topotecan combinations do not provide a survival advantage over topotecan alone in women with relapsed ovarian cancer.
Journal of Clinical Oncology 08/2008; 26(19):3176-82. · 18.37 Impact Factor
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Dominique Koensgen,
Dirk Stengel,
Antje Belau,
Peter Klare,
Guelten Oskay-Oezcelik,
Thomas Steck,
Oumar Camara,
Alexander Mustea, Harald Sommer,
Alexandra Coumbos,
Thomas Bogenrieder,
Werner Lichtenegger,
Jalid Sehouli
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ABSTRACT: Second-line treatment with paclitaxel and carboplatin enhances survival of women with platinum-sensitive recurrent ovarian cancer (ROC). However, because of its cumulative neurotoxicity, there is a strong demand for platinum-combinations with better therapeutic index. Because of its pharmacological properties, topotecan is a good adjunct to carboplatin in this setting, but its safety and efficacy remains to be defined.
Patients with platinum-sensitive ROC were eligible in this multicenter phase I/II study, stratified according to treatment-free interval (TFI). Dose level 0 consisted of topotecan 1 mg/m(2)/d1-3/q21d plus carboplatin AUC5/d3/q21d. DLT was defined as grade > or =3 neutropenia or thrombocytopenia or grade > or =3 non-hematological toxicity excluding alopecia, nausea and vomiting, accompanied by a treatment delay >1 week.
From June 2004 to August 2005, 26 patients were enrolled, receiving a total of 145 cycles of chemotherapy. MTD was reached at topotecan 0.75 mg/m(2) and carboplatin AUC5. We observed a single grade 4 leucopenia. There were 3 (12%), 15 (58%) and 8 (31%) events of grade 3/4 hematological anaemia, leucopenia, and thrombocytopenia. Response rate was 67% (95% CI 43-85), median progression-free survival 9.5 months (95% CI 7.3-12.0), median overall survival 19.4 months (95% CI 12.3-26.9). None of the toxicity or efficacy endpoints were associated with TFI.
Topotecan and carboplatin is a well tolerated novel doublet option for women with platinum sensitive ROC. We encourage further studies on this approach, but to limit the doses of topotecan to 0.75 mg/m(2)/d1-3 and carboplatin AUC 5/d3.
Cancer Chemotherapy and Pharmacology 08/2008; 62(3):393-400. · 2.83 Impact Factor
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ABSTRACT: Differences in overall survival (OS) and disease-free survival (DFS) between patients with invasive ductal (IDC) and invasive lobular breast cancer (ILC) are controversial.
The study population was selected from a database of 5,689 female patients with invasive breast cancer. In order to focus on the impact of tumour histology, all primary metastatic patients and patients with adjuvant chemotherapy or anti-hormonal treatment were excluded. Only patients with pure invasive lobular and invasive ductal histology were included.
Multivariate survival analyses of 2,058 eligible patients confirmed tumour histology as an independent prognostic factor for OS in invasive breast cancer (p = 0.046) but not for DFS (p = 0.599). Kaplan-Meier survival analysis of OS between IDC and ILC patients showed a statistically significantly better OS for patients with ILC (p = 0.0302). DFS was not statistically different (p = 0.6659) between IDC and ILC. Univariate survival analyses of tumour size, tumour grading and nodal status in our study population were highly statistically significant for OS and DFS (p < 0.0000).
Patients in our study population with ILC have significantly better OS than patients with IDC. Differences in DFS are not statistically significant.
Archives of Gynecology 05/2008; 279(1):23-8. · 0.91 Impact Factor
