Effects of physical exercise on breast cancer-related secondary lymphedema: a systematic review.

PURPOSE: The aim of this systematic review is to assess the effect of different types of exercise on breast cancer-related lymphedema (BCRL) in order to elucidate the role of exercise in this patient group. METHODS: A systematic data search was performed using PubMed (December 2016). The review is focused on the rehabilitative aspect of BCRL and undertaken according to the PRISMA statement with Levels of Evidence (LoE) assessed. RESULTS: 11 randomized controlled trials (9 with LoE 1a and 2 with LoE 1b) that included 458 women with breast cancer in aftercare were included. The different types of exercise consisted of aqua lymph training, swimming, resistance exercise, yoga, aerobic, and gravity-resistive exercise. Four of the studies measured a significant reduction in BCRL status based on arm volume and seven studies reported significant subjective improvements. No study showed adverse effects of exercise on BCRL. CONCLUSION: The evidence indicates that exercise can improve subjective and objective parameters in BCRL patients, with dynamic, moderate, and high-frequency exercise appearing to provide the most positive effects.

Economic burden of clinical trials in lung cancer in a German Comprehensive Cancer Center.

OBJECTIVES: The recent success of individualized lung cancer therapy has triggered fundamental changes in clinical research strategies. To date there is a strong focus on early proof of concept trials in genetically preselected small patient subgroups. This analysis focuses on the economic burden caused by such trials for advanced lung cancer patients in a German Comprehensive Cancer Center (CCC). METHODS: The profit margins between recruiting groups with ≤3 and >3 patients were compared. Clinical and economic data from clinical trials for advanced lung cancer (LC), pharma-sponsored trials (PhST) as well as investigator initiated trials (IIT), conducted between 2011 and 2015 at the Center for Integrated Oncology (CIO) Cologne, were analyzed using a profit-center calculation model. RESULTS: 161 patients were enrolled in 27 clinical trials. The key economic parameter determining costs and payments was the 'trial visits'. In comparison of the two groups (A≤3; B>3 patients enrolled) we found negative profit margins for the low recruiting group (€ -1444). Concerning the number of visits significant differences were found between PhST and IIT (p=0.009). Additionally, sub-analysis show structural differences in cost composition by conducting PhST and IIT. CONCLUSION: Trials with low patient numbers and IIT, do not cover the cost. To ensure adequate, cost-covering compensation by pharmaceutical companies CCCs have to thoroughly calculate the cost of early proof of concept trials. The findings of this study also underline the need for novel structures in public funding for investigator-initiated clinical trials in precision medicine.

Impact of aerobic exercise training during chemotherapy on cancer related cognitive impairments in patients suffering from acute myeloid leukemia or myelodysplastic syndrome - Study protocol of a randomized placebo-controlled trial.

Cancer related cognitive impairments (CRCI) are frequently reported by patients prior to, during and after medical treatment. Although this cognitive decline severely affects patients' quality of life, little is known about effective treatments. Exercise programs represent a promising supportive strategy in this field. However, evidence is sparse and existing studies display methodological limitations. In the planned study, 83 men and women newly diagnosed with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) will be randomized into one of three treatment groups. During 4weeks of induction chemotherapy with Anthracycline and Cytarabin patients allocated to exercise group will cycle 3×/week for 30min at moderate to vigorous intensity on an ergometer. Patients allocated to placebo group will receive a supervised myofascial release training (3×/week, approx. 30min) and patients at control group will get usual care. As primary endpoints a cognitive test battery will be conducted measuring performances depending on verbal/spatial memory and executive functioning. Secondary endpoints will be self-perceived cognitive functioning, as well as neurotrophic and inflammatory serum markers. All assessments will be conducted immediately after hospitalization and before chemotherapy is commenced, immediately before discharge of hospital after 4-5weeks as well as before continuing medical treatment 3-4weeks after discharge. This will be the first study investigating the impact of an aerobic exercise training on CRCI in AML/MDS patients. We hope that the study design and the state-of-the-art assessments will help to increase knowledge about CRCI in general and exercise as potential treatment option in this under investigated population.

Novel and emerging drugs for chronic lymphocytic leukemia.

During the last decades advanced treatment options for chronic lymphocytic leukemia have enabled the shift from rather ineffective palliative treatment to therapies that are aiming for long lasting complete remission and prolongation of survival. This remarkable progress was achieved by combining conventional chemotherapy with monoclonal antibodies such as rituximab and alemtuzumab. Despite this improvement, CLL remains an incurable disease and all patients will eventually relapse and become refractory to treatment. Allogeneic stem cell transplantation is the only curative option but is feasible only in a minority of patients due to the comorbidity and impaired physical fitness of many patients, since the mean age at first diagnosis lies between 70 and 75 years. Therefore, novel less-toxic therapeutic agents are needed, particularly for patients with comorbidities or high-risk cytogenetic abnormalities. Research in the field of CLL and growing understanding of the pathogenesis of B-cell lymphomas has produced a wide variety of new substances for different targets, e.g. different novel monoclonal antibodies, immunomodulatory agents and inhibitors targeting different kinases of B-cell receptor signalling cascade, such as Bruton tyrosine kinase (BTK) and phosphatidylinositol-3-kinase (PI3K). This article reviews novel drugs that were recently developed for the use in CLL. The agents discussed in this article were selected for having already shown preliminary evidence of clinical activity.

[Oncology and palliative medicine]. / Onkologie und Palliativmedizin.

Approximately one half of patients who receive the diagnosis of cancer still die as the result of their disease. To be able to adequately meet the patients and their families needs, it is essential that oncologists and palliative care physicians cooperate closely. How the recommendations of international institutions are concerning the cooperation between the fields of oncology and palliative care medicine can be approached is exemplified by the concepts developed in the Center for Integrated Oncology (CIO Cologne/Bonn) at the University Hospital in Cologne and discussed critically.

Chronotherapy with 5-fluorouracil and folinic acid in advanced colorectal carcinoma. Results of a chronopharmacologic phase I trial.

BACKGROUND: Chronotherapy with antineoplastic drugs is a rather new strategy of reducing cytotoxic side effects. Because the circadian timing of 5-fluorouracil (5-FU) was reported to result in a higher efficacy and lower toxicity, the authors conducted a chronopharmacologic Phase I trial with 5-FU and folinic acid (FA). METHODS: Eight patients with advanced colorectal cancer received 5-FU (initial dose of 500 mg/m2/day) and FA (20 mg/m2/day) as a continuous intravenous infusion over 5 consecutive days. Using a portable, ambulatory drug delivery system, 75% of the daily dose of 5-FU and FA were given from Oh00-7h00, and the remaining 25% from 7h00-24h00. Treatment courses were repeated after 28 days. Dose escalations of 250 mg/m2/day of 5-FU and 10 mg/m2/day of FA per course were performed in the absence of any toxicity greater than WHO (World Health Organization) grade 2. RESULTS: Dose-limiting toxicity WHO grade 3 was observed at a dose of 750 mg/m2/day of 5-FU and 30 mg/m2/day of FA in five, and 1000 mg/m2/day of 5-FU and 40 mg/m2/day of FA in two patients, respectively. One patient tolerated 1000 mg/m2/day of 5-FU and 40 mg/m2/day of FA, but the treatment was stopped before further dose escalation because of rapid disease progression. Mucositis was the dose-limiting toxicity in seven patients and diarrhea in two. Disease stabilization occurred in three patients and disease progression in five. Compared with conventional Phase I/II trials using a 5-day infusion regimen, the maximal tolerated dose of 5-FU and FA was slightly higher but significantly lower than in a chronotherapeutic trial that used a different, sinusoidal mode of drug application. CONCLUSION: Based on these results, the authors feel justified to caution that the circadian timing of 5-FU plus FA may not always allow the safe application of high dose levels. Future Phase I/II studies need to define whether specific drug delivery systems or schedules are necessary for chronotherapy with 5-FU and FA in patients with colorectal carcinoma.

Aspects of chronopharmacology and chronotherapy in children.

Pediatric studies involving chronopharmacology until now have been limited mainly to investigation of circadian patterns in children of 6 to 15 years. This means that: a. data on newborns and even on infants of one year or younger are not available, and b. other bioperiodicities, such as those of one year (infradian rhythms), have not yet been explored in older children. Biological time-related changes have been documented for phenytoin and theophylline with regard to their pharmacokinetics and for orciprenaline, ipratropium bromide, corticosteroids and anticancerous agents with regard to their effectiveness. Despite the small number of investigations performed to date, results indicate that: a. more comprehensive and precise characterization of pharmacokinetic and pharmacodynamic phenomena can be achieved by a chronopharmacological approach than the conventional one and, b. better therapeutics can be achieved using chronopharmacological facts since an appropriate timing of medicines with regard to biological rhythms is likely to enhance desired and/or reduce undesired effects.

Aspects of chronopharmacology and chronotherapy in pediatrics.

Pediatric chronopharmacological findings until now have been limited to circadian changes in children from ages 6 to 15 years. This means that data in newborns and even in infants of 1 year are not available and other bioperiodicities with periods of about-1-year (infradian rhythms) have not been explored in older children. Biologic time-related changes have been documented for phenytoin and theophylline with regard to pharmacokinetics, for orciprenaline with regard to bronchodilation, and for corticosteroids as well as anticancer agents with regard to their effectiveness. Despite the limited number of experiments performed to date, it is already possible to state that a chronopharmacological approach provides better precision in pharmacologic study than the conventional approach not using time-related data and better therapeutics can be achieved with the help of chronopharmacological facts since appropriate timing in administration of medicine usually enhances its desired and/or reduces its undesired effects.