August Zabernigg

Taste Alterations in Cancer Patients Receiving Chemotherapy: A Neglected Side Effect?

BACKGROUND Taste alterations (TAs) are a frequent but under-recognized treatment side effect in cancer patients undergoing chemotherapy (CT). CT regimens with different toxicity profiles may vary in their impact on TAs, but research on this topic is lacking. This study assesses the prevalence of TAs and their relation to sociodemographic and clinical variables, especially CT regimens. Furthermore, the association between TAs and quality of life (QOL) is investigated. PATIENTS AND METHODS TAs and QOL data were collected longitudinally in 197 cancer patients (lung cancer, 54.3%; pancreatic cancer, 19.3%; colorectal cancer, 26.4%; age, 65.2 +/-10.4 years; male, 57.4%) who were receiving CT at the Department of Internal Medicine at Kufstein County Hospital, giving rise to a total of 1,024 assessment times. Patients completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire and two additional questions taken from the EORTC item bank concerning TAs. Statistical analyses were performed using mixed-effect models. RESULTS The study showed that the prevalence of TAs in chemotherapy patients is alarmingly high (69.9%). There were clear differences in TA scores among treatment groups: patients receiving irinotecan reported significantly more TAs than patients in other treatment groups; patients receiving a combination of gemcitabine and a platinum agent reported the lowest TAs. Additionally, significant associations between TAs and several QOL dimensions were found, especially with appetite loss and fatigue. CONCLUSION The high prevalence of TAs and their impact on QOL in CT patients underscore the urgent need for increased attention to this side effect, both in research and in clinical practice.

Recombinant human granulocyte-macrophage colony-stimulating factor applied locally in low doses enhances healing and prevents recurrence of chronic venous ulcers

Background Chronic venous leg ulcers have a major medical and economic impact on the elderly worldwide. Healing of the large ulcers (>10 cm2 ) occurs only in two‐thirds of the patients and reulceration of healed ulcers recurs in one‐third within 1 year. Because both healing and relapse rate influence greatly a patient’s quality of life and the overall cost of treatment, every effort should be made to improve these two parameters.

The Computer-based Health Evaluation Software (CHES): a software for electronic patient-reported outcome monitoring

BackgroundPatient-reported Outcomes (PROs) capturing e.g., quality of life, fatigue, depression, medication side-effects or disease symptoms, have become important outcome parameters in medical research and daily clinical practice. Electronic PRO data capture (ePRO) with software packages to administer questionnaires, storing data, and presenting results has facilitated PRO assessment in hospital settings. Compared to conventional paper-pencil versions of PRO instruments, ePRO is more economical with regard to staff resources and time, and allows immediate presentation of results to the medical staff.The objective of our project was to develop software (CHES – Computer-based Health Evaluation System) for ePRO in hospital settings and at home with a special focus on the presentation of individual patient’s results.MethodsFollowing the Extreme Programming development approach architecture was not fixed up-front, but was done in close, continuous collaboration with software end users (medical staff, researchers and patients) to meet their specific demands. Developed features include sophisticated, longitudinal charts linking patients’ PRO data to clinical characteristics and to PRO scores from reference populations, a web-interface for questionnaire administration, and a tool for convenient creating and editing of questionnaires.ResultsBy 2012 CHES has been implemented at various institutions in Austria, Germany, Switzerland, and the UK and about 5000 patients participated in ePRO (with around 15000 assessments in total). Data entry is done by the patients themselves via tablet PCs with a study nurse or an intern approaching patients and supervising questionnaire completion.DiscussionDuring the last decade several software packages for ePRO have emerged for different purposes. Whereas commercial products are available primarily for ePRO in clinical trials, academic projects have focused on data collection and presentation in daily clinical practice and on extending cancer registries with PRO data. CHES includes several features facilitating the use of PRO data for individualized medical decision making. With its web-interface it allows ePRO also when patients are home. Thus, it provides complete monitoring of patients‘physical and psychosocial symptom burden.

Routine Clinical Use of Alemtuzumab in Patients With Heavily Pretreated B-Cell Chronic Lymphocytic Leukemia A Nation-Wide Retrospective Study in Austria

In previous studies, alemtuzumab demonstrated considerable activity in patients with previously treated B‐cell chronic lymphocytic leukemia (CLL), including fludarabine‐refractory disease. In this retrospective study, the authors evaluated the benefit of alemtuzumab monotherapy in unselected patients with advanced, previously treated CLL who received treatment in the routine clinical setting.

Clinical outcome of pretreated B-cell chronic lymphocytic leukemia following alemtuzumab therapy: a retrospective study on various cytogenetic risk categories

BACKGROUND Patients with B-cell chronic lymphocytic leukemia (CLL) with 17p deletion respond poorly to chemotherapy. This retrospective study evaluated the benefit of alemtuzumab monotherapy in unselected patients with advanced CLL in the various cytogenetic subgroups. PATIENTS AND METHODS Data were collected from 105 consecutive, pretreated, cytogenetically defined patients who had received alemtuzumab. Response, progression-free survival (PFS), and overall survival (OS) were assessed. RESULTS The hierarchic incidence of cytogenetic abnormalities was: 13q deletion (as sole abnormality), 18%; trisomy 12, 13%; 11q deletion, 19%; 17p deletion, 33%; and none of these, 16%. Overall response rate (ORR) was 43% in the total cohort and 49% in the subgroup of 17p-deleted patients (n = 35). From the start of alemtuzumab monotherapy, median PFS in the total cohort and in the subgroup of 17p-deleted patients was 7.0 and 7.1 months, respectively. Median OS in the total cohort and in 17p-deleted patients was 32.8 and 19.1 months, respectively. The poor-risk group of patients with CLL (i.e. fludarabine resistant, 17p deletion; n = 20) showed encouraging ORR, PFS, and OS (35%, 7.0 and 19.2 months, respectively). CONCLUSIONS Alemtuzumab was effective in treating patients with CLL across the cytogenetic categories evaluated, but there were differences. In patients with CLL with 17p deletion quite favorable ORR, PFS, and OS were achieved.

Rituximab maintenance versus observation alone in patients with chronic lymphocytic leukaemia who respond to first-line or second-line rituximab-containing chemoimmunotherapy: final results of the AGMT CLL-8a Mabtenance randomised trial

BACKGROUND In many patients with chronic lymphocytic leukaemia requiring treatment, induction therapy with rituximab plus chemotherapy improves outcomes compared with chemotherapy alone. In this study we aimed to investigate the potential of rituximab maintenance therapy to prolong disease control in patients who respond to rituximab-containing induction regimens. METHODS In this randomised, international, multicentre, open-label, phase 3 clinical trial, we enrolled patients who had achieved a complete response (CR), CR with incomplete bone marrow recovery (CRi), or partial response (PR) to first-line or second-line rituximab-containing chemoimmunotherapy and randomly assigned them in a 1:1 ratio (central block randomisation in the electronic case report form system) to either intravenous rituximab 375 mg/m(2) every 3 months, or observation alone, for 2 years. Stratification was by country, line of treatment, type of chemotherapy added to the rituximab backbone, and degree of remission following induction. The primary endpoint was progression-free survival. Efficacy analysis was done in the intention-to-treat population. This is the final, event-triggered analysis. Final analysis was triggered by the occurrence of 92 events. This trial is registered with ClinicalTrials.gov, number NCT01118234. FINDINGS Between April 1, 2010, and Dec 23, 2013, 134 patients were randomised to rituximab and 129 to observation alone. Median observation times were 33·4 months (IQR 25·7-42·8) for the rituximab group and 34·0 months (25·4-41·9) for the observation group. Progression-free survival was significantly longer in the rituximab maintenance group (47·0 months, IQR 28·5-incalculable) than with observation alone (35·5 months, 95% CI 25·7-46·3; hazard ratio [HR] 0·50, 95% CI 0·33-0·75, p=0·00077). The incidence of grade 3-4 haematological toxicities other than neutropenia was similar in the two treatment groups. Grade 3-4 neutropenia occurred in 28 (21%) patients in the rituximab group and 14 (11%) patients in the observation group. Apart from neutropenia, the most common grade 3-4 adverse events were upper (five vs one [1%] patient in the observation group) and lower (three [2%] vs one [1%]) respiratory tract infection, pneumonia (nine [7%] vs two [2%]), thrombopenia (four [3%] vs four [3%]), neoplasms (five [4%] vs four [3%]), and eye disorders (four [3%] vs two [2%]). The overall incidence of infections of all grades was higher among rituximab recipients (88 [66%] vs 65 [50%]). INTERPRETATION Rituximab maintenance therapy prolongs progression-free survival in patients achieving at least a PR to induction with rituximab plus chemotherapy, and the treatment is well tolerated overall. Although it is associated with an increase in infections, there is no excess in infection mortality, suggesting that remission maintenance with rituximab is an effective and safe option in the management of chronic lymphocytic leukaemia in early treatment phases. FUNDING Arbeitsgemeinschaft Medikamentöse Tumortherapie gemeinnützige GmbH (AGMT), Roche.

A randomized study comparing interferon (IFNα) plus low-dose cytarabine and interferon plus hydroxyurea (HU) in early chronic-phase chronic myeloid leukemia (CML)

This multicenter randomized phase III study was designed to compare the efficacy and toxicity of IFN alpha-2c (3.5 MU/d) in combination with either araC (10 mg/m(2) d1-10) or hydroxyurea (HU: 25 mg/kg per day) in newly diagnosed CML patients. A total of 114 patients were randomized. Following a median observation period of 36 (range 1-73) months the major cytogenetic response rates were 25 and 27% and the 4-year survival probabilities 62.5 and 63% for the araC and HU group, respectively. While the overall toxicity profile was comparable between both groups, patients in the HU arm exhibited a slightly higher degree of WHO grades 3 and 4 non-hematological toxicities.

Quality of life across chemotherapy lines in patients with cancers of the pancreas and biliary tract

BackgroundIn patients with cancers of the pancreatic and biliary tract quality of life (QOL) improvement is the main treatment goal, since survival can be prolonged only marginally. Up to date, knowledge on QOL impairments throughout the entire treatment process, often including several chemotherapy lines, is scarce. Our study aimed at investigating QOL trajectories from adjuvant treatment to palliative 3rd-line therapyMethodsPatients were included in routine electronic patient-reported outcome monitoring at Kufstein County Hospital at the time of diagnosis and assessed with the EORTC QLQ-C30 during each chemotherapy cycle.ResultsEighty out of 147 patients with pancreatic cancer or cancer of the bile ducts treated at the Kufstein County Hospital, fulfilled inclusion criteria and could be included in the study (mean age 67.4 years; 53.8% women). Physical, Emotional and Cognitive Functioning, and Global QOL deteriorated across chemotherapy lines, whereas Fatigue, Pain, Dyspnoea, Sleeping Disturbances, Diarrhoea, and Taste Alterations increased. With regard to Physical Functioning, Global QOL, Fatigue, Dyspnoea, Diarrhoea and Taste Alterations, the patients receiving adjuvant or 1st-line palliative chemotherapy did not differ significantly. Most patients in 2nd- or 3rd-line chemotherapy showed significantly higher impairments and symptom burden. However, patients under 1st and 2nd-line treatment showed stable QOL trajectories, whereas 3rd-line patients perceived substantial deteriorations.ConclusionsThe results suggest early palliative treatment initiation to stabilise QOL on a level as high as possible. The continuous QOL improvement during adjuvant treatment, probably reflecting post-operative recovery, may indicate that deleterious effects of adjuvant chemotherapy on QOL are highly unlikely.

Expertenempfehlung 2006 zur rationalen Zweitlinien-Therapie beim nicht-kleinzelligen Bronchuskarzinom

1 Medizinische Universität Innsbruck, Klinische Abteilung für Allgemeine Innere Medizin, Schwerpunkt Onkologie, Innsbruck, Österreich 2 KH der Elisabethinen Linz, Abteilung für Pneumologie, Linz, Österreich 3 Kaiser Franz Josef-Spital Wien, 3. Medizinische Abteilung – Zentrum für Onkologie und Hämatologie; LBI-ACR VIEnna & ACR-ITR VIEnna, Österreich 4 Klinikum Kreuzschwestern Wels, Abteilung für Lungenkrankheiten, Wels, Österreich 5 LKH Natters, Abteilung für Innere Medizin, Natters, Österreich 6 LKH Leoben, Abteilung für Lungenkrankheiten, Leoben, Österreich 7 Paracelsus Medizinische Privatuniversität, St. Johanns-Spital LKH Salzburg, Univ. Klinik für Innere Medizin III, Salzburg, Österreich 8 LKH Natters, Abteilung für Pneumologie, Natters, Österreich 9 Landesklinikum St.Pölten, 1. Medizinische Abteilung, St. Pölten, Österreich 10 LKH Feldkirch, Abteilung für Innere Medizin, Feldkirch, Österreich 11 SMZ West Baumgartner Höhe Otto Wagner Spital mit Pfelgezentrum, 2. Interne Lungenabteilung, Österreich 12 KH der Stadt Linz, Abteilung für Lungenkrankheiten, Linz, Österreich 13 Paracelsus Medizinische Privatuniversität, St. Johanns-Spital LKH Salzburg, Univ.-Klinik für Pneumologie, Salzburg, Österreich 14 Medizinische Universität Wien, Univ.-Klinik für Innere Medizin I, Wien, Österreich 15 Medizinische Universität Graz Univ.-Klinik für Innere Medizin, Klinische Abteilung für Onkologie, Graz, Österreich 16 LKH Feldkirch, Abteilung für Pneumologie, Feldkirch, Österreich 17 LKH Vöcklabruck, Abteilung für Innere Medizin, Vöcklabruck, Österreich 18 BKH Kufstein, Abteilung für Innere Medizin, Kufstein, Österreich

CYTOKINE PRIMING OF THE GRANULOCYTE RESPIRATORY BURST IN MYELODYSPLASTIC SYNDROMES

Increased susceptibility to infections in patients with myelodysplastic syndromes (MDS) is thought to be due to neutropenia as well as functional abnormalities of neutrophils. In the present study we examined the effect of two different stimulants (fMLP, PMA) and three cytokines (alphaTNF, G-CSF and GM-CSF), both singly and in combination on granulocyte (RB) in 25 MDS patients compared to seven healthy controls. Single fMLP and PMA-stimulation showed similar results for both groups. Preincubation with cytokines enhanced fMLP-stimulated RB in most MDS patients and controls, but in patients to a significantly lesser extent when compared to the control group (p < or = 0,05). Combinations of alphaTNF + GM-CSF and alphaTNF + G-CSF were highly synergistic in priming fMLP-stimulated burst in both groups. But again, as with the single cytokine priming this effect was markedly reduced in MDS patients compared to controls (p < or = 0,05). A specific priming defect for one of the cytokines or a cytokine combination could not be demonstrated. Serum alphaTNF levels were measured in 18 and neutrophil alkaline phosphatase (NAP) index in 23 patients. Results did not correlate with variations of the RB in MDS patients. We conclude that reduced alphaTNF, GM-CSF and G-CSF priming of granulocyte RB is a frequent finding in MDS and may contribute to the enhanced susceptibility to bacterial infections.