Significantly longer time to deterioration of quality of life due to CANKADO PRO-React eHealth support in HR+ HER2- metastatic breast cancer patients receiving palbociclib and endocrine therapy: primary outcome analysis of the multicenter randomized AGO-B WSG PreCycle trial.

BACKGROUND: The multicenter, randomized, phase IV, intergroup AGO-B WSG PreCycle trial (NCT03220178) evaluated the impact of CANKADO-based electronic patient-reported outcome (ePRO) assessment on quality of life (QoL) in hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer (MBC) patients receiving palbociclib and an aromatase inhibitor or palbociclib + fulvestrant. CANKADO PRO-React, a European Union-registered medical device, is an interactive autonomous application reacting to patient self-reported observations. PATIENTS AND METHODS: Between 2017 and 2021, 499 patients (median age 59 years) from 71 centers were randomized (2 : 1, stratified by therapy line) between an active version of CANKADO PRO-React (CANKADO-active arm) and a version with limited functionality (CANKADO-inform arm). A total of 412 patients (271 CANKADO-active; 141 CANKADO-inform) were available for analysis of the primary endpoint, time to deterioration (TTD) of QoL [10-point drop on the Functional Assessment of Cancer Therapy-General (FACT-G) score], using an Aalen-Johansen estimator for cumulative incidence function of TTD DQoL (QoL deterioration) with 95% pointwise confidence intervals (CIs). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and DQoL. RESULTS: In all patients [intention-to-treat (ITT)-ePRO], cumulative incidence of DQoL was significantly more favorable (lower) in the CANKADO-active arm (hazard ratio 0.698, 95% CI 0.506-0.963). Among first-line patients (n = 295), the corresponding hazard ratio was 0.716 (0.484-1.060; P = 0.09), and in second-line patients (n = 117) it was 0.661 (0.374-1.168; P = 0.2). Absolute patient numbers declined in later visits; FACT-G completion rates were 80% and higher until about visit 30. Mean FACT-G scores showed a steady decline from baseline and an offset in favor of CANKADO-active. No significant differences in clinical outcome were observed between arms: median PFS (ITT population) was 21.4 (95% CI 19.4-23.7) (CANKADO-active) and 18.7 (15.1-23.5) months (CANKADO-inform); median OS was not reached (CANKADO-active) and 42.6 months (CANKADO-inform). CONCLUSIONS: PreCycle is the first multicenter randomized eHealth trial demonstrating a significant benefit for MBC patients receiving oral tumor therapy when using an interactive autonomous patient empowerment application.

Patients' perspectives towards malignant ascites: results of a prospective observational trial regarding expectations, characteristics and quality of life-a study of the North-Eastern-German Society of Gynecological Oncology.

PURPOSE: Malignant ascites (MA) is a frequent and common symptom in (gyneco-) oncological patients. The present trial evaluated and assessed patients' characteristics, clinical features and the possible influence of MA on QoL measurements. METHODS: A prospective observational trial was conducted from Oct 2013 until Nov 2016. Therefore an interdisciplinary questionnaire was developed. Overall 250 patients with histological confirmed MA were included with different cancer entities (gynecological, gastrointestinal). The correlation of MA caused symptoms and QoL measurements was assessed using Kendall's tau b. Multivariable logistic regression models were applied to analyze the risks of symptoms or severe limitation in daily activities. RESULTS: 125 questionnaires could be analyzed. The majority of patients with MA had diagnosis of ovarian cancer (68.8%) and were under current cancer treatment (57.6%), mostly chemotherapy. Over 50% reported abdominal tension as major symptom, around 56% of the patients had MA when cancer was firstly diagnosed. Regression analysis showed that patients with MA above 2l were significantly more likely to be harmed in everyday activities. However, the age, gender, type of malignancy and the current treatment (chemotherapy vs. no chemotherapy) had no significant influence. CONCLUSION: MA has a significantly impact on QoL measurements in cancer patients and might influence everyday activities including basic needs like eating, walking and body care. There is a high need for more information and education of patients with MA.

Health resource utilisation associated with skeletal-related events in patients with bone metastases secondary to solid tumours: regional comparisons in an observational study.

Skeletal-related events (SREs) including spinal cord compression, pathologic fracture, and radiation or surgery to bone, occur frequently due to bone metastases in advanced cancer. This analysis of a multicentre, observational study was designed to describe cross-regional differences in health resource utilisation (HRU) of SREs in Western Europe and the US. Patients with bone metastases due to breast, lung or prostate cancer, or multiple myeloma who had experienced a SRE within the past 97 days were enrolled. Investigators recorded HRU associated with SREs, including hospitalisation and length of stay (LOS), outpatient visits, procedures and bisphosphonate use. This subanalysis includes 668 patients with solid tumours (US, n = 190 with 354 SREs; EU, n = 478 with 893 SREs). The rate of SREs associated with hospitalisation(s) was higher in the EU vs. the US (30% vs. 15%, P < 0.001) and LOS was longer in the EU [mean (SD) days/SRE: 19.87 (17.31) vs. 10.61 (9.39)]. However, the US was associated with higher rate of SREs with outpatient visits than the EU (88% vs. 74%, P < 0.0001) and more procedures [mean (SD)/SRE: 11.26 (7.94) vs. 6.91 (6.48)]. Bisphosphonates were less often used in the EU (65% vs. 76% of US, P = 0.0033). In patients experiencing SREs due to bone metastases, HRU patterns reflect regional diversity with a substantial burden in both regions.

Energy Ordering of Molecular Orbitals.

Orbitals are invaluable in providing a model of bonding in molecules or between molecules and surfaces. Most present-day methods in computational chemistry begin by calculating the molecular orbitals of the system. To what extent have these mathematical objects analogues in the real world? To shed light on this intriguing question, we employ a photoemission tomography study on monolayers of 3,4,9,10-perylene-tetracarboxylic acid dianhydride (PTCDA) grown on three Ag surfaces. The characteristic photoelectron angular distribution enables us to assign individual molecular orbitals to the emission features. When comparing the resulting energy positions to density functional calculations, we observe deviations in the energy ordering. By performing complete active space calculations (CASSCF), we can explain the experimentally observed orbital ordering, suggesting the importance of static electron correlation beyond a (semi)local approximation. On the other hand, our results also show reality and robustness of the orbital concept, thereby making molecular orbitals accessible to experimental observations.

ABC3 Consensus Commented from the Perspective of the German Guidelines: Third International Consensus Conference for Advanced Breast Cancer (ABC3), Lisbon, 07. 11. 2015.

The Third International Consensus Conference for Advanced Breast Cancer ABC3 on the diagnosis and treatment of advanced breast cancer was held in Lisbon from 5 to 7 November 2015. This year the focus was the treatment of metastatic breast cancer (stage IV) - including the patient perspectives. Important topics were questions relating to quality of life, the care for long-term survivors as well as the management of disease-related symptoms and treatment-based side effects. The use of standardised tools to assess individual treatment success and the benefits of new substances were important points for discussion. The diagnosis and treatment of inoperable locally advanced breast cancer were discussed two years ago during the ABC2 consensus 1. A working group of German breast cancer experts commented on the results of the ABC panellists, paying particular attention to the German guidelines (AGO, S3, DGHO) on the diagnosis and treatment of breast cancer 2, 3, 4, 5 in Germany.

Neurocognitive function, brain-derived neurotrophic factor (BDNF) and IL-6 levels in cancer patients with depression.

BACKGROUND: Increased IL-6 and decreased brain-derived neurotrophic factor (BDNF) levels have been implicated in the pathophysiology of depression. The objective was to assess the influence of BDNF and IL-6 on cognitive function and depression in patients with cancer. METHODS: Serum BDNF and plasma IL-6 were measured in patients with metastatic cancer. Diagnosis of depression was established according to DSM-IV criteria. Cognitive function was assessed by the Verbal Learning and Memory Test (VLMT). RESULTS: A total of 59 patients were recruited in this study. Only IL-6 levels were significantly elevated in patients with clinical depression (35.7 vs. 6.9 pg/ml; p<0.001). There were no differences in hemoglobin levels (p=0.3) or BDNF levels (p=0.16). Patients with clinical depression showed significant impairment of short-term memory (STM) (24.4 vs. 37.5; p=0.01), but not of long-term memory (LTM) (3.9 vs. 2.8; p=0.3). STM was dependent on the level of BDNF and younger age (b=0.60; p=0.001; b= -0.63; p=0.003, respectively). IL-6 was not only strongly associated with depression, but was an independent predictor of BDNF level as well (b= -0.50; p=0.01). LTM was associated only with a good KPS (b=0.47; p=0.037). Hemoglobin levels and the prior number of chemotherapy lines were not predictive of memory performance. CONCLUSIONS: Low BDNF is associated with cognitive impairment, STM, in patients with cancer, however no influence on depression could be found. IL-6 is strongly associated with depression and an independent predictor of BDNF levels.

Exploring three-dimensional orbital imaging with energy-dependent photoemission tomography.

Recently, it has been shown that experimental data from angle-resolved photoemission spectroscopy on oriented molecular films can be utilized to retrieve real-space images of molecular orbitals in two dimensions. Here, we extend this orbital tomography technique by performing photoemission initial state scans as a function of photon energy on the example of the brickwall monolayer of 3,4,9,10-perylene tetracarboxylic dianhydride (PTCDA) on Ag(110). The overall dependence of the photocurrent on the photon energy can be well accounted for by assuming a plane wave for the final state. However, the experimental data, both for the highest occupied and the lowest unoccupied molecular orbital of PTCDA, exhibits an additional modulation attributed to final state scattering effects. Nevertheless, as these effects beyond a plane wave final state are comparably small, we are able, with extrapolations beyond the attainable photon energy range, to reconstruct three-dimensional images for both orbitals in agreement with calculations for the adsorbed molecule.

Breast Cancer Update 2014 - Focus on the Patient and the Tumour.

The therapy for patients with breast cancer has developed markedly in the past ten years. Our understanding of the molecular biology of tumours and the characteristics of the patients has shaped the recent advances. In this review we present the latest knowledge about the therapy for breast cancer. There are new tests and options not only in the field of anti-HER2 therapy but also in the management of triple negative and hormone receptor-positive patients. Comprehension of prognosis and therapeutic response to chemotherapies is little by little helping to define patient groups who will not respond to chemotherapy or who do not need treatment because their prognosis is extremely good. In the field of anti-HER2 therapy, work is continuing on the development of drugs suitable for and able to overcome trastuzumab resistance. For hormone receptor-positive cancers, we now have a better understanding of which therapy groups will benefit from which anti-endocrine drugs, and which will be able to overcome a possible resistance (treatment of the PI3K pathways, inhibition of the cell cycle). Molecular tests are still being evaluated with regard to the clinical situations in which they may have the greatest relevance for therapeutic decision-making; however, evidence is also increasing as to the fields in which good predictions for the prognosis can be obtained. On the whole, more work is needed to promote our understanding of the new developments in diagnostics and therapy and to involve both physicians and patients equally in the procedures.

Biomarkers in Patients with Metastatic Breast Cancer and the PRAEGNANT Study Network.

Progress has been made in the treatment of metastatic breast cancer in recent decades, but very few therapies use patient or tumor-specific characteristics to tailor individualized treatment. More than ten years after the publication of the reference human genome sequence, analysis methods have improved enormously, fostering the hope that biomarkers can be used to individualize therapies and offer precise treatment based on tumor and patient characteristics. Biomarkers at every level of the system (genetics, epigenetics, gene expression, micro-RNA, proteomics and others) can be used for this. This has led to changes in clinical study designs, with drug developments often only focusing on small or very small subgroups of patients and tumors. The screening and registration of patients and their molecular tumor data has therefore become very important for the successful completion of clinical studies. This new form of medicine presents particular challenges for patients and physicians. Even in this new age of genome-wide analysis, the focus should still be on the patients' quality of life. This review summarizes recent developments and describes how the PRAEGNANT study network manages the aforementioned medical challenges and changes to create a professional infrastructure for patients and physicians.

A survey of treatment approaches of malignant ascites in Germany and Austria.

BACKGROUND: Malignant ascites (MA) is a common manifestation of advanced cancer. Currently, there are no evidence-based guidelines for the management of MA. We conducted a survey with physicians throughout Germany and Austria, to get an overview of current approaches and opinions in the treatment of MA. METHODS: One hundred and twenty-eight medical oncologists (MO), gastroenterologists (GE), and gynecologists (GYN) completed an electronic questionnaire consisting of 33 questions. RESULTS: Ninety percent of the physicians were from Germany and 10% from Austria; 48% of those were MO, 30% were GYN, and 14% were GE. Most physicians treated an average of 34 patients (pts)/year with MA. Twenty-six percent of these pts suffered from ovarian, 20% from pancreatic, 17% from gastric, and 14% from colorectal cancer. The majority of the physicians associated MA with poor prognosis (92%) and significant reduction in quality of life (87%). One third felt that MA was a contraindication for full dosing of systemic chemotherapy. Paracentesis (PC) was performed in 70% of pts with symptom relieve and quality of life being the main reasons. Almost half of the pts required 3-5 PC, 50% even more than 5 PC during the course of their disease. Only 15% of pts needed multiple PC per week; the majority (79%) needed the procedure either once a week or every 14 days. In 61% of pts, 3-5 L of ascites fluid was drained. Only in 8%, 5 L and more were removed. Volume substitution with IV albumin was performed in 40% of pts. Most pts (55%) had to stay 1-3 h in a healthcare facility for the procedure. However, 21% had to stay ≥1 day. While almost all physicians (89%) performed a PC at some point in the treatment of MA, 75% felt that a systemic chemotherapy and 55% thought a concomitant diuretic therapy were a necessary adjunct. Seven percent of the pts received a targeted treatment with catumaxomab. CONCLUSIONS: Repeated PC is the main pillar of treatment of MA; its effect is only temporary and requires significant hospital resources. Further treatment strategies of MA have to be evaluated in prospective studies. Targeted therapies like catumaxomab and VEGF inhibitors should be integrated into these.

The interplay between interface structure, energy level alignment and chemical bonding strength at organic-metal interfaces.

What do energy level alignments at metal-organic interfaces reveal about the metal-molecule bonding strength? Is it permissible to take vertical adsorption heights as indicators of bonding strengths? In this paper we analyse 3,4,9,10-perylene-tetracarboxylic acid dianhydride (PTCDA) on the three canonical low index Ag surfaces to provide exemplary answers to these questions. Specifically, we employ angular resolved photoemission spectroscopy for a systematic study of the energy level alignments of the two uppermost frontier states in ordered monolayer phases of PTCDA. Data are analysed using the orbital tomography approach. This allows the unambiguous identification of the orbital character of these states, and also the discrimination between inequivalent species. Combining this experimental information with DFT calculations and the generic Newns-Anderson chemisorption model, we analyse the alignments of highest occupied and lowest unoccupied molecular orbitals (HOMO and LUMO) with respect to the vacuum levels of bare and molecule-covered surfaces. This reveals clear differences between the two frontier states. In particular, on all surfaces the LUMO is subject to considerable bond stabilization through the interaction between the molecular π-electron system and the metal, as a consequence of which it also becomes occupied. Moreover, we observe a larger bond stabilization for the more open surfaces. Most importantly, our analysis shows that both the orbital binding energies of the LUMO and the overall adsorption heights of the molecule are linked to the strength of the chemical interaction between the molecular π-electron system and the metal, in the sense that stronger bonding leads to shorter adsorption heights and larger orbital binding energies.

Influence of comorbidity, age and performance status on treatment efficacy and safety of cetuximab plus irinotecan in irinotecan-refractory elderly patients with metastatic colorectal cancer.

BACKGROUND: We investigated the influence of comorbidity, Eastern Cooperative Oncology Group (ECOG) performance status and age on the efficacy and safety profile of cetuximab and irinotecan in elderly irinotecan-pretreated patients with mCRC. METHODS: 497 patients with mCRC were entered in the database of this non-interventional study (NIS). Comorbid conditions were recorded. RESULTS: A total of 247 and 250 patients aged <65 and >65 years, respectively, with a median age of 66 y were documented; 78% of the patients showed a reduced ECOG status. Grade III/IV toxicities occurred in 18% of patients without any difference between age groups although older patients had more comorbidities with a higher Charlson Comorbidity Index (CCI) (p = 0.002). Skin rash was strongly related to response (p = 0.006). Age, line of therapy, ECOG, gender and CCI had no influence on response. The objective response rates were similar: 38.1% for age <65 years versus 36.4% for age >65 years (p = 0.57). Progression-free survival (PFS) did not differ between patients 18-65 years (6.0 months) and patients >65 years (6.2 months; p = 0.99). Only PS had a negative impact on PFS (hazard ratio (HR): 0,499; 95% confidence interval (CI) 0.34-0.72; p=0.002), whereas the presence of skin toxicity (grade>1) influenced PFS and response rate (RR) positively (HR: 2.04; 95% CI, 1.6-2.6; p<0.001). CONCLUSIONS: Only PS and age had a negative influence on PFS irrespective of CCI or age. There were no significant differences in response rate and safety profile for elderly patients when treated with cetuximab and irinotecan. Comorbidities and age had no influence on efficacy or toxicity.

Health resource utilization associated with skeletal-related events in patients with bone metastases: Results from a multinational retrospective - prospective observational study - a cohort from 4 European countries.

BACKGROUND: Skeletal-related events (SREs; pathologic fracture, radiation or surgery to bone, spinal cord compression) frequently occur in patients with advanced cancer with bone metastases/lesions. Limited data on the associated patient and economic burden are available to aid in resource planning and evaluating treatment options. METHODS: Patients with bone metastases/lesions secondary to breast, lung or prostate cancer or multiple myeloma; with at least one SRE within 97 days prior to enrollment; life expectancy of at least 6 months; and Eastern Cooperative Oncology Group performance status 0, 1 or 2 were recruited. Information on health resource utilization (HRU; including number/duration of hospitalizations, outpatient visits, procedures), attributed by investigators to be associated with a SRE, was collected retrospectively for up to 97 days prior to enrollment and prospectively for up to 18-21 months. RESULTS: A total of 631 patients contributing 1282 SREs, were enrolled across Germany, Italy, Spain and the United Kingdom. Approximately a third of all SREs required an inpatient stay. Mean duration of inpatient stay for patients with SREs requiring one ranged from 8.4 to 41.1 days across all countries and SRE types. CONCLUSION: All types of SREs are associated with substantial HRU burden. Preventing SREs by using the best therapeutic options available may help to reduce the burden to patients and healthcare systems.

Cost of skeletal-related events in European patients with solid tumours and bone metastases: data from a prospective multinational observational study.

OBJECTIVES: Patients with bone metastases often experience skeletal-related events (SREs: radiation or surgery to bone, pathologic fracture, and spinal cord compression). This study examined health resource utilization and costs associated with SREs. METHODS: Data presented are from the European cohort (Germany, Italy, Spain, and the UK) of patients with solid tumours enrolled in a multi-national, prospective, observational study in patients with solid tumours or multiple myeloma. Patients with Eastern Cooperative Oncology Group score 0-2 and life expectancy ≥6 months, who experienced an SRE up to 97 days before enrolment, were eligible. Health resource utilization associated with SREs (including number/length of inpatient stays, numbers of procedures and outpatient visits) were collected through chart review for up to 97 days before enrolment and prospectively during follow-up. Country-specific cost calculations were performed. RESULTS: In total, 478 eligible patients contributed 893 SREs to this analysis. Radiation to bone occurred most frequently (66% of total). Spinal cord compression (7%) and surgery to bone (10%) were the least common events, but most likely to require inpatient stays. The most costly SREs were also spinal cord compression (mean per SRE across countries, €4884-€12,082) and surgery to bone (€3348-€9407). Inpatient stays were the main cost drivers. LIMITATIONS: Health resource utilization used to calculate the costs associated with SREs may have been under-estimated as a result of exclusion of patients with low performance status or life expectancy; unavailable information and exclusion of resource consumption associated with pain. Thus, the estimate of associated costs is likely to be conservative. CONCLUSIONS: SREs result in considerable health resource utilization, imposing a substantial financial burden driven by inpatient stays. Treatments that prevent/delay SREs may help ease this burden, thereby providing cost savings across European healthcare systems.

Influence of age, performance status, cancer activity, and IL-6 on anxiety and depression in patients with metastatic breast cancer.

Depression and anxiety are the core disorders causing emotional distress in patients (pts) with metastatic breast cancer. The aim of our study was to screen metastatic breast cancer outpatients for anxiety and depression, and to investigate the influence of age, Karnofsky Performance Status (KPS), cancer activity, and inflammation as represented by IL-6 levels on these two mood disorders. Pts treated with chemotherapy for metastatic breast cancer (n = 70) were assessed using the Hospital Anxiety and Depression Scale (HADS) for symptoms (scores 0-21) and caseness (score ≥11) of clinical depression and anxiety. Blood samples for IL-6 concentrations were collected at 10:00 a.m. A total of 22 (31.4 %) pts were diagnosed with caseness of clinical depression and 23 (32.9 %) pts with clinical anxiety, while 12 pts were diagnosed positive for both mood disorders. Depression and anxiety were positively but moderately correlated (Spearman's r (2) = 0.24, p < 0.001). IL-6 was significantly correlated with symptoms of depression (r (2) = 0.42, p < 0.001) and to a lesser extent to symptoms of anxiety (r (2) = 0.16, p = 0.001). In addition, IL-6 was positively associated with tumor progression (p < 0.001). Multiple linear regression analysis showed that tumor progression (standardized b = 0.226, p = 0.047), symptoms of anxiety (b = 0.292, p = 0.016), and IL-6 (b = 0.314, p = 0.007) were independently associated with clinical depression, whereas anxiety was linked to tumor progression (b = 0.238, p = 0.030), symptoms of depression (b = 0.407, p < 0.001) and age (b = -0.381, p < 0.001), but not to IL-6 (b = 0.168, p = 0.134). Even though a positive correlation between depression and anxiety exists, clinical parameters like age, cancer activity, KPS, and IL-6 do influence depression and anxiety differently. Unlike clinical depression, anxiety is not associated with increased IL-6 levels, however, shows a reciprocal correlation with age.

Cetuximab-based therapy in elderly comorbid patients with metastatic colorectal cancer.

BACKGROUND: Clinical trials under-represent patients (pts) >65 years. Non-interventional studies (NISs) help to evaluate therapies in daily practice. This NIS evaluates efficacy and safety of cetuximab in combination with chemotherapy in metastatic colorectal cancer (mCRC) pts aged >65 years vs ≤ 65 years. METHODS: A total of 657 pts were recruited into the NIS and analysed applying descriptive statistics and χ(2) or Fisher's exact test. RESULTS: A total of 309 and 305 pts aged ≤ 65 and >65 years, respectively, were documented; 80% showing a reduced ECOG status of 1-2 and 95% having received at least one palliative treatment. Cetuximab was combined with irinotecan according to approval status. Grade III/IV toxicities occurred in 20% of pts without any difference between age groups although the older pts had significantly more pre-existing comorbidities (P=0.001). A total of 64.2% of the pts developed skin rash, which was strongly related to response (P<0.0002) without any difference between age groups (P=0.34). The objective response rates were 37.9% for ages 18-65 years vs 35.4% for >65 years. Progression-free survival (PFS) did not differ between pts 18-65 years old (6.5 months) in comparison with pts >65 years (7.0 months). In a multivariate analysis only ECOG status had a negative impact on PFS (HR: 0,675; 95% Cl, 0.53-0.87; P=0.0019). CONCLUSION: This NIS reports one of the largest mCRC collectives >65 years and reduced performance status. Cetuximab has a similar efficacy and safety profile for pts aged ≤ 65 and >65 years.

Advances in Breast Cancer - Looking Back over the Year.

Treatment options as well as the characteristics for therapeutic decisions in patients with primary and advanced breast cancer are increasing in number and variety. New targeted therapies in combination with established chemotherapy schemes are broadening the spectrum, yet not every new, promising combination achieves a better result. New data from the field of pharmacogenomics point to prognostic and predictive factors that take not only the properties of the tumour but also the genetic disposition of the patient into consideration. Current therapeutic decision-making is thus based on a combination of classical clinical and modern molecular biomarkers. Health-economic concerns are also being taken into consideration more frequently, meaning political decisions may also become a factor. This review presents the trends over the past year.

Breast Cancer 2012 - New Aspects.

Treatment options as well as the characteristics for therapeutic decisions in patients with primary and advanced breast cancer are increasing in number and variety. New targeted therapies in combination with established chemotherapy schemes are broadening the spectrum, however potentially promising combinations do not always achieve a better result. New data from the field of pharmacogenomics point to prognostic and predictive factors that take not only the properties of the tumour but also inherited genetic properties of the patient into consideration. Current therapeutic decision-making is thus based on a combination of classical clinical and modern molecular biomarkers. Also health-economic aspects are more frequently being taken into consideration so that health-economic considerations may also play a part. This review is based on information from the recent annual congresses. The latest of these are the 34th San Antonio Breast Cancer Symposium 2011 and the ASCO Annual Meeting 2012. Among their highlights are the clinically significant results from the CLEOPATRA, BOLERO-2, EMILIA and SWOG S0226 trials on the therapy for metastatic breast cancer as well as further state-of-the-art data on the adjuvant use of bisphosphonates within the framework of the ABCSG-12, ZO-FAST, NSABP-B34 and GAIN trials.

First safety and response results of a randomized phase III study with liposomal platin in the treatment of advanced squamous cell carcinoma of the head and neck (SCCHN).

BACKGROUND: Cisplatin is one of the most active chemotherapeutic agents used in the treatment of advanced squamous cell carcinoma of the head and neck (SCCHN). However, its clinical efficacy is limited by its renal and hematotoxicity profile. In a randomized, multicenter phase III trial, we replaced conventional cisplatin by a liposomal formulation of cisplatin (lipoplatin) and compared the safety and efficacy profiles of patients in the two treatment arms. PATIENTS AND METHODS: Main inclusion criteria were: histologically confirmed SCCHN, age between 18-75 years with sufficient renal function. Main endpoints for this interims analysis were hemato- and nephrotoxicity. First response data were collected. RESULTS: Forty-six patients were evaluable for outcome and toxicity. Grade III and IV hematotoxicity were more frequent in the cisplatin arm (31.7% vs. 12%), with grade IV leucopenia occurring in 22.2%. However, 16% of the patients in that treatment arm experienced grade III anemia compared to only 9.5% treated with the cisplatin regimen. A total 4% of the patients in the lipoplatin arm developed grade IV neuropathy, whereas in the cisplatin arm, 19% developed grade III neuropathy and none developed grade IV. The renal toxicity profile of both drugs also showed marked differences. In the cisplatin arm, 23.8% of patients suffered grade III toxicity. In contrast, no grade III or IV renal toxicity occurred in patients treated with lipoplatin. The efficacy results showed 38.8% objective partial remission in the cisplatin arm vs. 19% in the lipoplatin arm. However 64% of the patients achieved stable disease while being treated with lipoplatin/5-fluorouracil (5-FU), vs. 50% in the cisplatin/5-FU arm. CONCLUSION: Liposomal cisplatin seems to reduce both the renal and hematological toxicity to a clinically relevant extent as compared to conventional cisplatin. The clinical benefit rate is similar for both regimens.