Purpose
The aim of this work was to evaluate exercise behavior and physical fitness of advanced lung cancer patients shortly after primary diagnosis.
Methods
Between November 2013 and December 2016, ...advanced lung cancer patients (
n
= 227, mean age 62.2 years) were enrolled shortly after diagnosis and 211 patients were tested for endurance capacity (six-minute walk test) and strength performance (maximum voluntary isometric contraction of upper and lower extremities). Current and previous exercise and walking behavior were assessed using a self-reported questionnaire regarding type, frequency, intensity, and duration. Paired Student’s
t
tests were used to compare physical fitness to reference data. The relation of potential determinants with physical fitness was assessed using linear regression analysis.
Results
Exercise behavior was superior in the year before diagnosis compared to the time of study enrollment. Patients reduced frequency, intensity, and duration of sports/exercise after their lung cancer diagnosis. We observed significantly lower endurance capacity (
p
< .01) and strength performance in lower extremities (
p
< .01) in male and female patients compared to age and sex-matched reference data. We found significant correlations of previous exercise and walking behavior with physical fitness shortly after diagnosis in patients with advanced lung cancer.
Conclusion
Patients with advanced lung cancer showed impaired physical fitness regarding endurance and strength capacity. The strong decline in participation of sports/exercise shortly after diagnosis supports early implementation of physical exercise during anti-cancer treatment.
Trial registration
ClinicalTrials.gov
NCT02055508
Patients with advanced stage non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) often experience multidimensional impairments, affecting quality of life during their course of ...disease. In lung cancer patients with operable disease, several studies have shown that exercise has a positive impact on quality of life and physical functioning. There is limited evidence regarding efficacy for advanced lung cancer patients undergoing palliative treatment. Therefore, the POSITIVE study aims to evaluate the benefit of a 24-week exercise intervention during palliative treatment in a randomized controlled setting.
The POSITIVE study is a randomized, controlled trial investigating the effects of a 24-week exercise intervention during palliative treatment on quality of life, physical performance and immune function in advanced, non-operable lung cancer patients. 250 patients will be recruited in the Clinic for Thoracic Diseases in Heidelberg, enrolment begun in November 2013. Main inclusion criterion is histologically confirmed NSCLC (stage IIIa, IIIb, IV) or SCLC (Limited Disease-SCLC, Extensive Disease-SCLC) not amenable to surgery. Patients are randomized into two groups. Both groups receive weekly care management phone calls (CMPCs) with the goal to assess symptoms and side effects. Additionally, one group receives a combined resistance and endurance training (3x/week). Primary endpoints are quality of life assessed by the Functional Assessment of Cancer Therapy for patients with lung cancer (FACT-L, subcategory Physical Well-Being) and General Fatigue measured by the Multidimensional Fatigue Inventory (MFI-20). Secondary endpoints are physical performance (maximal voluntary isometric contraction, 6-min walk distance), psychosocial (depression and anxiety) and immunological parameters and overall survival.
The aim of the POSITIVE trial is the evaluation of effects of a 24-week structured and guided exercise intervention during palliative treatment stages. Analysis of various outcomes (such as quality of life, physical performance, self-efficacy, psychosocial and immunological parameters) will contribute to a better understanding of the potential of exercise in advanced lung cancer patients. In contrast to other studies with advanced oncological patients the POSITIVE trial provides weekly phone calls to support patients both in the intervention and control group and to segregate the impact of physical activity on quality of life.
ClinicalTrials.gov NCT02055508 (Date: December 12, 2013).
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This phase III study compared efficacy and safety of topotecan-cisplatin (TP) versus topotecan-etoposide (TE) versus cisplatin-etoposide (PE) in chemo-naïve extensive disease small-cell lung cancer ...patients.
Seven hundred and ninety-five previously untreated patients were randomly assigned to TP (topotecan 1mg/m2 IV, d1–5; cisplatin 75mg/m2 IV, d5; n = 358), PE (cisplatin 75 mg/m2 IV, d1; etoposide 100 mg/m2 IV, d1–3; n = 345) or TE (topotecan 1mg/m2 IV, d1–5; etoposide 80 mg/m2 IV, d3–5; n = 92). Primary endpoint was superiority of TP compared with PE, with the possibility to switch to a noninferiority test.
The TE arm was closed after recommendations by the Independent Data Safety Monitoring Board. Median survival was similar and met the predefined endpoint of noninferiority of TP to PE (44.9 versus 40.9 weeks; p = 0.40). One-year survival rate showed 39.7% for TP versus 36.1% for PE (p = 0.29). Median time to progression was significantly longer with TP (27.4 versus 24.3 weeks, p = 0.01). Overall response rates were significantly higher for TP (55.5% versus 45.5%, p = 0.01).
Hematologic toxicity was slightly higher for TP regarding G 3/4 neutropenia (35.7/35.8%), G 3/4 thrombocytopenia (18.7/4.8%), G 3/4 anemia (11.6/6.7%), febrile neutropenia (2.0/2.7%), sepsis (1.7/1.2%), and toxicity-related deaths (5.2/2.7%).
TP is noninferior to PE in overall survival and superior in time to progression and overall response rates. Because of slightly worse toxicity profile TP is not a first-line standard treatment for patients with extensive disease small-cell lung cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hydroxychloroquine as a weak basic compound with two amines is strongly enriched in cell compartments with low pH, suggesting that modification of gastric pH by coadministered proton pump inhibitors ...might reduce its solubility and absorption and thus its efficacy in patients. We addressed this question in a single‐center, open‐label, randomized, parallel drug‐drug interaction trial in healthy adults (EudraCT No. 2020‐001470‐30). All participants received a single oral dose of 400‐mg hydroxychloroquine, and one group additionally received 40 mg of pantoprazole once daily for 9 days dosed to steady state. Whole‐blood samples were collected for 72 hours, and hydroxychloroquine was quantified by liquid chromatography–tandem mass spectrometry. Primary endpoints were whole‐blood hydroxychloroquine areas under the concentration‐time curve from 0 to 72 hours (AUC0‐72h) and peak concentrations (Cmax). Unpaired 2‐sided t‐tests of the log transformed pharmacokinetic parameters were performed to compare both groups. Twenty‐four participants (12 per group) were included. Hydroxychloroquine AUC0‐72h and Cmax did not differ between groups without and with pantoprazole (arithmetic mean; AUC0‐72h, 7649 ng/ml • h, and 8429 ng/ml • h, P = .50; Cmax, 448 ng/mL and 451.5 ng/mL, P = .96, respectively). Pantoprazole did not alter hydroxychloroquine absorption, indicating that proton pump inhibitors do not affect its bioavailability.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Introduction: Physical exercise intervention programs show beneficial effects in early stage cancer patients during and after treatment. There is also growing evidence that physical exercise is safe ...and feasible for advanced cancer patients but knowledge is limited.
Areas covered: This review provides an overview of randomized controlled exercise trials implemented in palliative care settings with advanced cancer patients. A comprehensive literature search was carried out in PubMed (MEDLINE), CINAHL, and the Cochrane Library. Six articles providing data of 590 patients met the predefined inclusion criteria. Mainly resistance exercise was applied and duration of interventions was between 8 and 16 weeks.
Expert commentary: Beneficial effects for exercise patients were reported for both physical and psychological outcomes. However, general exercise recommendation for patients undergoing palliative treatment cannot be derived from the six analyzed studies. This is due to large heterogeneity of the applied exercise programs, included patient groups and performed assessment methods.
OBJECTIVEChemoprevention trials have shown that celecoxib reduces adenoma recurrence but can cause cardiovascular toxicity. In this pilot study, we evaluated associations between genetic variation in ...several candidate pathways (e.g. prostaglandin synthesis) and adenoma recurrence and cardiovascular and gastrointestinal toxicities.
METHODSGenotyping analysis was carried out on 117 Israeli colorectal adenoma patients who participated in the Prevention of Colorectal Sporadic Adenomatous Polyps trial. Reassessment followed after 3 years on celecoxib and after 2 years from termination of treatment with celecoxib. Efficacy (absence of colorectal adenomas) was measured by colonoscopy at years 1, 3, and 5. Toxicities were assessed by investigators during celecoxib treatment and by self-report post-treatment. A linkage disequilibrium-based selection algorithm (r≥0.90, MAF≥4%) identified 255 tagSNPs in 25 analyzed candidate genes. Genotyping was performed by using Illumina GoldenGate technology.
RESULTSMultiple genetic variants were associated with adenoma recurrence and toxicity. Genetic variability in COX1, COX2, and ALOX12/15 genes played a role in adenoma recurrence, particularly among patients on placebo. More gene variants (especially variants in PGES, CRP, SRC, and GPX3) were associated with increased risk for cardiovascular toxicity and symptoms, compared with gastrointestinal toxicity and symptoms. The increased risk for cardiovascular toxicity/symptoms associated with the SRC gene variants (rs6017996, rs6018256, rs6018257) ranged from 6.61 (95% confidence interval 1.66–26.36, P<0.01) to 10.71 (95% confidence interval 1.96–58.60, P<0.01).
CONCLUSIONGenetic polymorphisms in multiple inflammation-related genes appear to interact with celecoxib on adenoma recurrence and its attendant toxicity, particularly cardiovascular toxicity/symptoms. Larger studies validating these pharmacogenetic relationships are needed.
Abstract
Background: Chemoprevention trials have shown that Celecoxib, a selective COX-2 inhibitor can reduce adenoma recurrence but can also increase risk of cardiac toxicity. Therefore, in this ...pilot study, we evaluated the associations between genetic variation in several candidate pathways (e.g. prostaglandin, arachidonic acid and leukotriene synthesis), the incidence of adenoma recurrence as well as toxicity (any, gastrointestinal, cardiac, and non-gastrointestinal/non-cardiac toxicities). Methods: This analysis includes 119 Israeli patients with colorectal adenoma who participated in the Prevention of Colorectal Sporadic Adenomatous Polyps (PreSAP) trial. Reassessment followed after ∼3 years on Celecoxib, followed by 2 years off drug. Incidence of colorectal adenomas was measured by colonoscopy at years 1, 3, and 5. The presence of any, gastrointestinal, cardiac and non-gastrointestinal/non-cardiac toxicities was assessed by investigators for the on-treatment period and collected by patient self-report after treatment. A linkage-disequilibrium-based tagSNP selection algorithm (r2≥0.90, MAF≥4%) identified tagSNPs in candidate pathways. Genotyping was performed using IlluminaTM GoldenGate bead-based genotyping technology. Results: Multiple variants were associated with adenoma recurrence and toxicities. Variability, particularly in COX-1 (rs10306164, rs1236913, rs1330344, rs3119773), COX- 2 (rs4648268), and ALOX12 (rs2073438, rs2292350) played a major role in adenoma recurrence risk among patients on placebo compared to patients on Celecoxib. The highest risk was observed for the COX-1 rs3119773 variant (1890 G>A intron 2) (HR=4.65, 95%CI 1.71-12.64, p=0.0026). Variants in COX2 (rs2206593, rs2745557), EGFR (rs1558544, rs17336919), ALOX15 (rs2619112, rs2619118, rs4796535), SRC (rs6018027, rs7269342), SEPP1 (rs230819, rs230820), and WNT6 (rs6747776, rs6754599) genes were associated with any toxicity. In contrast to gastrointestinal toxicity, a larger number of gene variants (especially variants in PGES, CRP, SRC and GPX3) were associated with increased risk of cardiac toxicity. The increased risk of cardiac toxicity associated with the SRC gene variants (rs6017996, rs6018256, rs6018257) ranged from 7- to 11-fold. Conclusion: Genetic polymorphisms in multiple inflammation-related genes appear to mediate the effect of Celecoxib on adenoma recurrence and the resultant toxicity, particularly cardiac toxicity. Identification of these genetic variants can potentially help in the provision of tailored and optimum care for colorectal adenoma patients. Larger studies validating these pharmacogenetic relationships are warranted.
Citation Format: {Authors}. {Abstract title} abstract. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1004. doi:1538-7445.AM2012-1004
Abstract 4471
Guidelines recommend glucocorticoids and splenectomy as standard 1st and 2nd line treatments for chronic ITP. We sought to find out how German ITP-patients are treated in respect of ...these guidelines.
Members of a patient support association >18 y with self-reported history of chronic ITP (>6 mo) were surveyed. A questionnaire was developed from literature review with clinician and patient input, and administered on-line.
123 questionnaires were evaluated. Age (median 51 years) and gender distribution (38% m, 62% f) are comparable to surveys from other countries. 70% of patients had chronic ITP for more than 5 years and 50% a “usual” platelet count of < 50.000/μl (20% < 30.000/μl). 69% had hematomas or petechiae within the last 12 months, 45% had oropharyngeal bleeds, and 11% had been admitted to a hospital within this year. 88% had received or receive glucocorticoids, 28% were splenectomized. IVIg was given to 55%, rituximab to 22%, anti-D to 11%, cyclosporine to 7%. Complementary and alternative medical treatments had been used by 36%. 38 women were under the age of 50 and 14 (36%) reported that they had been advised not to become pregnant. 23 became pregnant and 10 (44%) required ITP-treatment during their pregnancy.
Glucocorticoids are the most common therapy for chronic ITP but complementary and alternative treatments already come second and less than 1/3 of the patients are splenectomized. This and the frequent use of complementary medicines suggests dissatisfaction with conventional therapeutic approaches. Many patients receive off-label therapies (rituximab, anti-D, cyclosporine are not licensed for ITP in Germany). There is a major need for adequate counseling and care for pregnant ITP-patients.
Matzdorff:GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AMGEN: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Baxter: Consultancy, Honoraria. Off Label Use: Rituximab for chronic ITP Complementary medicines for ITP. Hummler:GlaxoSmithKline: Employment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract 4451
Chronic ITP is a rare disorder. Steroids are the usual 1st line therapy. Despite published guidelines there is considerable variation in 2nd and 3rd line therapies. Objective of this ...study was to compare therapies and patient-perceived treatment effects between the US and a European country (Germany).
Members of a US and a German patient support group >18 y with self-reported history of chronic ITP (>6 mo) were surveyed. A questionnaire was developed from literature review with clinician and patient input, and administered on-line. Demographics, patient histories, ITP therapy-related effects and side effects were recorded.
712 subjects participated in both surveys (US 589, GER 123). Most were female (US 78%, GER 63%), and diagnosed with ITP for ≥5 years (US 59%, GER 70%). Many subjects had a minimum platelet count under 50.000/μl during the last year (US 68%, GER 66%), dry (US 79%, GER 72%) and wet purpura (US 46%, GER 64%). Corticosteroids were the most frequently reported therapy (USA 92%, GER 86%) followed by IVIg (USA 55%, GER 55%), splenectomy (USA 39%, GER 28%), rituximab (USA 36%, GER 22%, note: GER public health insurance does not reimburse rituximab). Patients experienced steroid treatment as particularly bothersome (both US and GER 90% report weight gain, moon face). For rituximab US patients reported most commonly fatigue, tiredness, weakness (47%), GER patients infusion reactions (55%). For splenectomy US patients reported most commonly scarring (67%), GER patients antibiotic use (38%). 56% of splenectomized GER pts. would not recommend this procedure to other patients.
Responding patients in the US and GER survey are both heavily pre-treated and report comparable side effects of those treatments. 1st line (steroid) and emergency treatment (IVIg) does not differ while 2nd/3rd line therapies vary. US patients are more likely to receive invasive (splenectomy) or even “off-label” therapies (rituximab) to have a chance of cure, presumably to reduce the financial burden of their disease. GER public health insurance covers all costs (except rituximab) and this might explain why GER patients are more willing to delay or even forego splenectomy. This implies that GER patients might be more inclined to try thrombopoietin receptor agonists before splenectomy. Future studies need to consider the effect of different health care systems on treatment decisions.
Matzdorff:GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AMGEN: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxter: Consultancy, Honoraria. Off Label Use: Rituximab for chronic ITP. Hummler:GlaxoSmithKline: Employment. Grotzinger:GlaxoSmithKline: Employment. Horblyuk:GlaxoSmithKline: Employment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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