How to break bad news and how to learn this skill: results from an international North-Eastern German Society for Gynecological Oncology (NOGGO) survey among physicians and medical students with 1089 participants

BACKGROUND: Delivering bad news to patients is one of the most challenging tasks in medical practice. Despite its great relevance to patients, relatives, and medical staff, there is a paucity of data pertaining to training, experience, expectations, and preferences of physicians and medical students on breaking bad news. METHODS: We conducted an international survey in Germany, Switzerland, and Austria using an online questionnaire among physicians and medical students. RESULTS: A total of 786 physicians and 303 medical students completed the survey. Physicians stated that 32.7% deliver bad news several times a week and 45.2% several times a month. Difficulties controlling their emotions (35.1%) and remaining professional (43.4%) were the greatest challenges for physicians. Delivering bad news is associated with feelings of anxiety, both among experienced physicians (median of 3.8 out of 10.0) and medical students (median of 5.3). Conveying bad news is a burden to physicians and consequently has a substantial impact on their job satisfaction. All participants reported the need for more communication training concerning this subject. Only 49.5% of medical students and 67.3% of physicians mentioned having learned adequate communication skills. Our data demonstrate that communication training decreases the level of anxiety and increases the feeling of self-confidence towards breaking bad news. Preferred educational tools were seminars with simulation (students: 71.4%, physicians: 49.5%), observing more senior faculty (students: 57.4%, physicians: 55.1%), and supervision and feedback sessions (students: 36.3%, physicians: 45.7%). The largest barriers regarding education on communication were limited time (students: 77.0%, physicians: 74.9%) and missing awareness of supervisors (students: 60.6%, physicians: 41.1%). CONCLUSIONS: Our study showed a great need for systematic training and education in breaking bad news among physicians and medical students. Hospitals, medical schools, and postgraduate training programs are strongly encouraged to fill this gap, and improve sustainable doctor-patient communication to overcome the psychological burden for physicians.

The Endocrine Treatment Landscape for Patients with HR+ HER2- Early-stage Breast Cancer in Germany Before the Introduction of CDK4/6 Inhibitor Therapy - A Real-World Analysis.

Introduction: While premenopausal patients with HR+ HER2- early breast cancer are treated with tamoxifen +/- ovarian suppression with a GnRH analog or an aromatase inhibitor (AI) + GnRH, the majority of postmenopausal women receive an AI due to its higher efficacy compared to tamoxifen. As the introduction of CDK4/6 inhibitors into the treatment of early-stage breast cancer with a higher risk of recurrence will probably result in a shift in the endocrine treatment landscape, the question is what treatment did potential candidates for CDK4/6 inhibitors in Germany receive before CDK4/6 inhibitors were available. Patients and Methods: As part of a retrospective multicenter analysis, anonymized data were collected of patients with HR+ HER2- early-stage breast cancer who received endocrine therapy in the period between 10/2021 and 03/2022. Potential candidates for CDK4/6 inhibitor treatment were classified into different risk cohorts using the inclusion criteria of the NATALEE and monarchE trials. Results: The data of 238 patients from 29 different centers were analyzed. While 20.6% of patients met the monarchE criteria, the subgroup which met the NATALEE inclusion criteria consisted of 46.2% of patients. 53.8% of patients did not meet the inclusion criteria for either the NATALEE or the monarchE trial. More than half of the patients did not receive chemotherapy. 28.6% of patients in the whole cohort were premenopausal. 67.6% of premenopausal women received neo-/adjuvant chemotherapy. 61.8% of premenopausal patients received tamoxifen as adjuvant endocrine therapy, 19.1% received an AI + GnRH and 10.3% were treated with tamoxifen + GnRH. Conclusion: Despite the high percentage of premenopausal patients who received aggressive treatment in the form of chemotherapy, only one third of premenopausal patients received GnRH in addition to their standard endocrine therapy. Studies carried out at a later point in time and registry studies will be necessary to see how the endocrine therapy landscape in Germany has changed following the introduction of CDK4/6 inhibitors.

Real-world evidence of NEPA, netupitant-palonosetron, in chemotherapy-induced nausea and vomiting prevention: effects on quality of life.

Aim: To determine quality of life, effectiveness and safety of oral netupitant-palonosetron (NEPA)-based antiemetic prophylaxis in the real-world setting. Materials & methods: Prospective, noninterventional study in adults receiving highly or moderately emetogenic chemotherapy and NEPA for three cycles. NEPA was administered per summary of product characteristics. Results: A total of 2429 patients enrolled, 2173 were evaluable. 'No impact on daily life' due to vomiting was reported by 85%/82% of patients in the highly emetogenic chemotherapy/moderately emetogenic chemotherapy groups in cycle 1, with rates of 54%/59% for nausea. Overall, complete response rate was 89%/87%/83% in the acute/delayed/overall phases. NEPA was well tolerated. Conclusion: NEPA had beneficial effects on the quality of life of a heterogeneous group of cancer patients and was safe and effective in the real-world setting.

Expectations and preferences of patients with primary and relapsed ovarian cancer to maintenance therapy: A NOGGO/ENGOT-ov22 and GCIG survey (Expression IV).

BACKGROUND: Maintenance therapy induces remission and prolongs disease free interval in primary and recurrent ovarian disease. For the treatment decision making process, aspects of quality of life and patients' preferences are crucial, despite the fact that scientific data are lacking. Therefore, we conducted this European-wide study in patients with ovarian cancer. METHODS: A 25 item questionnaire was provided to ovarian cancer patients via the internet or as a paper version in 10 European countries (Austria, Belgium, France, Germany, Italy, Romania, Slovenia, Finland, Turkey, and Spain). Data recorded were demographics, tumor stage, therapy after firstline and recurrent disease, preferences for administration, and expectations concerning maintenance therapy. RESULTS: Overall, 1954 patients participated from September 2013 to March 2016; 42% had recurrent disease. Most patients (98%) with primary epithelial ovarian cancer underwent surgery followed by chemotherapy (91%). Almost one-third of participants (29%) were receiving maintenance therapy whereas 45% had only heard of it. For 70% of patients with primary epithelial ovarian cancer, they heard about maintenance therapy from their doctor, 10% heard about maintenance therapy from other patients, and 8% from the internet. The main source of information about maintenance therapy in patients with epithelial ovarian cancer relapse was from the treating physician (72%), from other patients (8%), and from the internet (7%). For patients undergoing maintenance therapy, the four most disturbing adverse effects were polyneuropathy (37%), nausea (36%), hair loss (34%), and vomiting (34%). The main objective of maintenance treatment, as perceived by patients, was to increase the chances of cure (73%), improvement in quality of life (47%), and delay in tumor growth (37%). Many patients were willing to undergo maintenance therapy until tumor progression (38%) and 39% would prefer oral administration. No significant differences were detected in the cross country subanalysis regarding expectations of maintenance therapy and patients with primary or relapsed ovarian cancer. CONCLUSION: Patients with ovarian cancer were willing to accept maintenance therapy of prolonged duration and preferred oral administration. There is still a gap between the efficacy of maintenance therapy and patient expectations. Patients need more information on the adverse effects and treatment goals of maintenance therapy to avoid misunderstandings.

Participation of elderly gynecological cancer patients in clinical trials.

BACKGROUND: Elderly patients are underrepresented in clinical trials in gynecological cancer, even though they are disproportionally often affected. This study aimed to evaluate the disposition and apprehension of elderly patients toward study participation. METHODS: 112 elderly gynecological cancer patients (median age 70) were surveyed in a multicenter cross-sectional study. Besides fitness, state of disease, education and domestic situation, questions aimed at the general willingness to participate in a clinical trial. Personal reasons for refusal and anticipated advantages/disadvantages that might evolve from participation were inquired. RESULTS: Willingness to participate in a clinical study was generally high (72%, 74/102). Reasons for potential study participation were: 'better monitoring of the disease' (67.1%), 'better medical care' (46.1%), 'to help medical research' (44.7%), 'better medication' (35.5%) and 'because of my doctor's recommendation' (22.4%). Reasons for potential refusal were: 'too time consuming' (24.4%), 'fear of side effects' (21.8%), 'misuse as experimental animal' (18%), 'long distance to clinic' (14.1%) and 'too little or unclear information' (10.3%). 37.2% (29/78) of the patients stated that they had 'no objection' at all against study participation. The question if patients anticipated having a longer life due to study participation was answered with 'yes' or 'rather yes' in 42% (38/90); 28.9% answered 'no' or 'rather no' (29% undecided). No statistical significant relation between willingness to participate in a study and general fitness (p = 0.133), education (p = 0.122), age (p = 0.474) or domestic situation (p = 0.123) could be observed in a multivariate logistic regression model. CONCLUSIONS: Elderly patients are generally willing to participate in clinical studies, in our cohort regardless of their fitness. Benefits of participation seem to be unclear among a majority of potential study participants. Therefore, it might be decisive to provide more general information regarding benefits and safety for elderly patients in a clinical trial.

Development of a Questionnaire for Monitoring Risk Factors for Chemotherapy-induced Nausea and Vomiting - A NOGGO Pilot Study.

BACKGROUND: Despite many years of clinical research and development, nausea and vomiting remain challenging toxicities related to chemotherapy. The aim of our study was to clarify the significance of non-pharmacological, patient-related risk factors for chemotherapy-induced nausea and vomiting. Furthermore, we aimed to develop a unique patient-related risk score predicting nausea and vomiting in patients with gynaecological malignancies under chemotherapy. MATERIALS AND METHODS: Based on a literature research, 27 risk factors were identified and a preliminary questionnaire was generated. This questionnaire was assessed in 20 patients diagnosed with gynaecological malignancies. RESULTS: The majority of questions were easy to understand and could be answered unambiguously. Questions regarding alcohol consumption and nutrition needed optimization due to problems with suitable answer option finding. CONCLUSION: Patient-related factors are currently not included when selecting antiemetic prophylaxis in patients under chemotherapy. After a few amendments, our questionnaire will be used in prospective study. To our knowledge, this is the first practicable questionnaire addressing these issues.

Treosulfan in the Treatment of Advanced Ovarian Cancer - Results of a German Multicenter Non-interventional Study.

BACKGROUND: Data on routine systemic treatment of patients with ovarian cancer are currently available only to a limited degree. The alkylating agent treosulfan is approved in oral (p.o.) and intravenous (i.v.) form for the treatment of ovarian carcinoma. The present non-interventional study analyzed the clinical use of treosulfan in Germany, evaluating the mode of application, toxicity, and response and survival rate. PATIENTS AND METHODS: Two hundred and forty-eight ovarian cancer patients in 57 Centers, who received treosulfan mainly either i.v. (5,000-8,000 mg/m(2) d1, q21d or q28d) or p.o. (400-600 mg/m(2) d1-14 or 21, q28d) for at least one therapy cycle were evaluable and were included in the study. RESULTS: With a median age of 70 years (range=36-92 years), predominantly elderly patients received treosulfan treatment. Most participants presented serous histology (131, 52.8%) and advanced-stage FIGO III (122, 49%) or IV (55, 22%) disease. Median ECOG status was 1 (range=0-2), whereas cardiac co-morbidity was common (31%). Treosulfan was usually administered as second- (26%), third- (21%) or fourth-line (17%) therapy. Two hundred and one patients received i.v. and 47 p.o. TREATMENT: The most common reason for dose modifications was due to hematological toxicity (46%). The main reason for a therapy discontinuation was progressive disease (38.5%). Response was observed in 25.8% of participants, disease stabilization in 28.6 % and progress in 45.6%. The median progression-free and overall survival was 196 and 405 days, respectively. CONCLUSION: In predominantly elderly and heavily pre-treated patients with recurrent ovarian cancer, treosulfan featured a clinical relevant efficacy and well-manageable, mostly hematological, toxicity, which resulted in a positive therapeutic index.

Ovarian cancer: Ion channel and aquaporin expression as novel targets of clinical potential.

Ovarian cancer is associated with limited overall survival, due to problems in early detection and therapy. Membrane ion channels have been proposed to play a significant, concerted role in the cancer process, from initial proliferation to metastasis, and promise to be early, functional biomarkers. We review the evidence for ion channel and aquaporin expression and functioning in human ovarian cancer cells and tissues. In vitro, K(+) channels, mainly voltage-gated, including Ca(2+)-activated channels, have been found to control the cell cycle, as in other cancers. Voltage-gated, volume-regulated and intracellular Cl(-) channels have been detected in vitro and in vivo and shown to be involved in proliferation, adhesion and invasion. Evidence for 'transient receptor potential', voltage-gated sodium and calcium channels, which have been shown to contribute to pathogenesis of other carcinomas, is also emerging in ovarian cancer. Aquaporins may be involved in cell growth, migration and formation of ascites via increased water permeability of micro-vessels. It is concluded that functional expression of ion channels and their regulation by steroid hormones and growth factors are an integral part of ovarian cancer development and progression. Furthermore, ion channels may be involved in multidrug resistance, commonly associated with treatment of ovarian cancer. We propose that ion channel studies can facilitate our understanding of the pathobiology of ovarian cancer and, ultimately, can serve as viable novel targets for its clinical management.

A prospective multicenter study of treosulfan in elderly patients with recurrent ovarian cancer: results of a planned safety analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 %). CONCLUSION: 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.

First patient treated with a re-challenge of catumaxomab in recurrent malignant ascites: a case report.

In the past, treatment for malignant ascites focussed on symptomatic relief or treatment of the underlying disease. A promising option evolved with catumaxomab (Removab(®)) in 2009. Since catumaxomab is a bispecific, trifunctional antibody with mouse-rat origin, so far repeated treatment cycles were not an option due to the occurrence of human anti-drug antibodies (HADA). Nevertheless, the good results obtained so far raised the question whether a repeated treatment cycle with catumaxomab could be feasible and effective. We report on a 74-year-old female patient with breast cancer and peritoneal carcinomatosis. To our knowledge, this is the first patient world-wide to be treated with a repeated cycle of catumaxomab. HAMA (human anti-mouse antibodies) values were identified in blood and ascites samples. Ascites samples were also stained to identify and quantify cells, positive for EpCAM (epithelial cell adhesion molecule) and CD45. The patient tolerated the second cycle without unexpected side effects and remained puncture-free for another 45 days. Analysis of blood and ascites revealed a quick increase in HAMA values in the blood samples after 1 week, but considerably lower HAMA values and delayed increase in the ascites samples. Also a distinct and continuous decrease of EpCAM-positive cells was observed in the ascites samples under treatment. A strong increase in CD45-positive cells was detected after the beginning of the second cycle, with a consecutive decline toward the end. This first experience suggests that a repeated cycle of catumaxomab might be feasible and effective. As a consequence, a phase II trial (SECIMAS) was initiated.

Cancer patients and the Internet: a survey of the 'Quality of Life' Working Groups of the Arbeitsgemeinschaft für Internistische Onkologie and the Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie.

BACKGROUND: Patient-reported outcomes, such as quality of life (QoL) assessment, are becoming more important as endpoint in clinical trials and for decision making regarding new anticancer product approvals. Nevertheless, numerous obstacles exist regarding the implementation of QoL assessment in the daily practice of medical oncologists. Regular, computerized or internet home-based QoL assessments could be a step forward. METHODS: Using a 15-item paper questionnaire, we conducted a survey among 1580 cancer patients regarding their willingness to use internet QoL assessment, and collected personal data and information about current disease and performance status. RESULTS: Younger patients (i.e. ≤65 years) significantly more often had internet access (78% versus 36%; χ(2) test, p < 0.001). Moreover, the availability of internet access correlated with higher education levels. 55% of all polled patients are willing to use an internet-based QoL assessment tool, regardless of the type of internet access, whereas almost two-thirds (n = 600; 65%) of patients with their own internet access would be willing to use it for providing statements about QoL. Of these, especially younger patients in good health status with higher education degrees indicated their willingness to use such tools. CONCLUSION: These data may serve as a basis for identifying patient groups willing to participate in pilot projects to evaluate the implementation of internet-based regular assessment of QoL in cancer.

Predictive factors in relapsed ovarian cancer for complete tumor resection.

AIM: The aim of this study was to identify predictive factors for complete tumor resection in patients with relapsed ovarian cancer. PATIENTS AND METHODS: All patients with first relapse of ovarian cancer who underwent secondary cytoreduction at our center between September 2000 and April 2006 were evaluated according to a validated intraoperative documentation tool. Predictive factors were identified by logistic regression following the Cox regression model. RESULTS: Overall, 177 consecutive patients (pts) were analyzed. The median age at first diagnosis was 55 years (range, 23-83 years). The complete tumor resection rate was 44.6%. Predictive factors that correlated with an adverse surgical outcome in terms of residual tumor were ascites <500 ml (Odds ratio, OR=0.3; 95% Confidence interval, CI=0.1-0.8 p<0.05), tumor involvement of the small bowel (OR=0.22; 95% CI=0.07-0.71 p<0.05), tumor spread in the upper abdomen (OR=0.33; 95% CI=0.1-0.9 p<0.05) and platinum resistance (OR=0.1, 95% CI=0.06-0.5 p<0.01). Serous tumor histology (OR=5.8) appeared to have a protective effect. Age and initial FIGO stage were of no predictive significance. CONCLUSION: Platinum-sensitive patients without ascites, no intestinal tumor involvement, tumor restricted to middle and lower abdomen, and of serous papillary histology have significantly higher complete tumor resection rates. Prospective studies are warranted to evaluate the predictive value of these factors.

Bevacizumab in heavily pre-treated and platinum resistant ovarian cancer: a retrospective study of the North-Eastern German Society of Gynaecologic Oncology (NOGGO) Ovarian Cancer Study Group.

BACKGROUND: Bevacizumab is an agent with a tolerable safety profile which was described to be effective in recurrent ovarian cancer in recent phase I and phase II trials. But it remains unclear if these characteristics can translate to the very special collective of heavily pre-treated ovarian cancer patients. The present analysis was conducted to answer questions regarding safety and efficacy for the use of bevacizumab in these patients. PATIENTS AND METHODS: A single-center, retrospective chart review was performed including all patients with histologically confirmed ovarian cancer and treatment with bevacizumab between 1981 and 2008. Data documentation was performed with an internet-based documentation tool (Alcedis Med, Alcedis, Gießen, Germany). All data were analyzed using SPSS version 16.0 (SPSS Inc., Chicago, IL, USA). RESULTS: Overall, 15 patients who were treated with bevacizumab outside of a clinical study were identified. A total of 134 cycles of bevacizumab were applied, with a median of 8.9 cycles per patient. All 15 patients had platinum-resistant disease at the time of treatment, with a median of 5.4 prior lines of chemotherapy (range 1-7). The best response under treatment with bevacizumab was classified as partial response in 2 patients (13.3%). Stable disease was found in 6 (40%) and progressive disease in 7 (46.7%) patients. The median time to progression was 6.6 months and the median overall survival was 15.0 months from the first cycle of bevacizumab. At the time of analysis 3 patients were still alive and 1 patient had been lost to follow-up. No gastrointestinal perforations or treatment related deaths were observed. Severe adverse events included 3 fistulas (20%), 1 impaired wound healing (6.6%) and 1 severe blood pressure crisis (6.6 %). DISCUSSION: Despite previous experience of a high rate of bowel perforations in patients with ovarian cancer treated with bevacizumab, no perforation was observed in this analysis despite the fact that this collective was a heavily pretreated and platinum resistant subgroup. The most severe possible side effect in this group was the occurrence of fistula, which might suggest that bevacizumab is a therapy option with an acceptable safety profile, even though the rate of fistulas is higher than reported in previous studies. This might again be related to the nature of this very special subgroup of heavily pretreated patients. CONCLUSION: The results of this analysis suggest that bevacizumab might be an efficient therapy option in the setting of heavily pre-treated ovarian cancer with a tolerable safety profile even in this very special collective.

Pros and cons for systemic therapy in recurrent ovarian cancer.

Due to the high recurrence rates of ovarian carcinoma, the treatment of recurrent disease is currently one of the most challenging topics in the clinical setting. Ovarian cancer patients who do not respond to initial chemotherapy or who relapse after achieving a response are generally incurable. Treatment goals after failure of first-line treatment for ovarian cancer include: (a) controlling or preventing disease-related symptoms, (b) maintaining quality of life by choosing an effective treatment with low toxicity potential, and (c) prolonging progression-free survival. In contrast to the adjuvant situation in which prospective randomized phase III trials have established the current standard, only a few randomized trials are available for patients with recurrent disease. In addition, a series of agents has been shown to have clinical activity in recurrent ovarian cancer, including topotecan, pegylated liposomal doxorubicin, gemcitabine and oral etoposide. It has also been demonstrated that re-treatment with a platinum drug and taxane has been associated with a significant clinical activity in patients with "sensitive" (treatment-free interval >6 months) recurrent disease. The role of antihormonal therapy is still unclear. These possible treatments for recurrent ovarian cancer require prospective randomized trials comparing efficacy, toxicity and quality of life.

Current role and future aspects of topotecan in relapsed ovarian cancer.

BACKGROUND: Ovarian cancer is the fifth leading cause of cancer deaths in women. It is associated with a poor prognosis, as the majority of patients present with advanced disease and relapse after radical surgery, and following chemotherapy with carboplatin and paclitaxel. OBJECTIVE: To review the role of topotecan in the treatment of advanced and relapsed ovarian cancer, and the efficacy and safety of novel dosing regimens and formulations of topotecan. It will also discuss further options of combination of topotecan with other cytotoxic agents and targeted therapies. RESEARCH DESIGN AND METHODS: The authors searched for relevant references in the MEDLINE database and in congress abstracts of the American Society of Clinical Oncology. RESULTS: Topotecan is an established second-line therapy for advanced and relapsed ovarian cancer; a regimen of 1.5 mg/m(2)/day 1-5 has been approved in the USA and many other western countries. Topotecan is well tolerated; associated haematological toxicity is generally manageable, reversible and non-cumulative. A number of alternative dosing regimens and formulations have been investigated in an attempt to improve the toxicity profile of topotecan without compromising anti-tumour activity. A novel oral formulation of topotecan has shown clinical promise in patients with advanced and relapsed disease. Administration of i.v. topotecan on a weekly basis produced encouraging results in several phase II trials, with less haematological toxicity and similar response rates to the day 1-5 regimen. Also, recent early studies demonstrate that topotecan is effective in combination with several other therapeutic agents in the relapsed setting. CONCLUSION: The peer-reviewed literature reports that topotecan is an effective, well tolerated treatment option for relapsed ovarian cancer.

Brain metastases in relapsed epithelial ovarian cancer after chemotherapy with pegylated liposomal doxorubicin.

BACKGROUND: Brain metastases in epithelial ovarian cancer (EOC) occur rarely and are associated with a poor prognosis. No significant risk factors have been identified and no evidence-based treatment guidelines are currently available. CASE REPORT: A 56-year-old EOC patient presented with seizure at the Emergency Department eleven days after completion of fourth-line chemotherapy with pegylated liposomal doxorubicin (PLD). A computed tomography (CT) scan revealed multiple metastases. The patient received radiotherapy with a total dose of 30.8 Gy and 8 cycles of paclitaxel resulting in stable disease. Based on the current literature, treatment options are discussed. CONCLUSION: Therapeutic options for brain metastases include radiation, systemic or intrathecal chemotherapy, surgery or a combination regime. Since the effectiveness of systemic chemotherapy remains controversial, current research focuses on developing new anticancer drugs that penetrate the blood-brain barrier in order to prevent and/or treat brain metastases.

New aspects of adjuvant therapy in endometrial cancer: current standards and future directions.

Endometrial cancer is one of the most common gynaecological cancers in western countries. Most women are diagnosed at an early stage of the disease and can be cured by surgery alone. In patients with poor prognostic factors or an advanced disease, the chance of progression-free survival and overall survival is greatly diminished. Adjuvant chemotherapy is effective for patients with advanced disease. The combination of doxorubicin and cisplatin achieves overall response rates ranging from 34 to 60%, and the addition of paclitaxel seems to improve the outcome of patients with advanced disease, but it induces a significantly higher toxicity. A Gynecologic Oncology Study Group phase-III study is currently exploring the triplet paclitaxel+doxorubicin+cisplatin plus G-CSF vs. the less toxic combination of paclitaxel+carboplatin. Ongoing and planned phase-III trials are evaluating newer combination chemotherapy regimens, a combination of irradiation and chemotherapy and the implementation of targeted therapies with the goal of improving the tumour control rate and quality of life.