[Fentanyl buccal tablets in the treatment of breakthrough cancer pain. German cohort of a pan-European multicentre study]. / Fentanyl-Buccaltabletten in der Behandlung von Durchbruchschmerzen : Deutsche Kohorte einer paneuropäischen multizentrischen Studie.

BACKGROUND: Patients with breakthrough cancer pain (BtCP) experience significant limitations in their physical, mental and social functions. Fentanyl buccal tablets (FBT), a rapid onset opioid, are specifically indicated for the treatment of BtCP. METHOD: The results of the German cohort of a pan-European study are presented. This included cancer pain patients from 32 German centers. Patients were on continuous opioid medication and had at least 4 BtCP episodes per day. After randomization to 2 groups, 66 patients started the titration of FBT with 100 µg (group A) and 200 µg (group B), respectively. All patients were titrated to their individual EAD, which could be a maximum of 800 µg FBT per episode, regardless of the initial dose. Subsequently, up to 8 BtCP episodes were treated with this EAD. At baseline and after treatment, patients assessed the effects of BtCP on their functional status using the modified BPI-7S and answered questions about the efficacy, simplicity, and ease-of-use of the treatment. RESULTS AND CONCLUSIONS: Successful titration was achieved by 49 patients (74.2%). There was no statistically significant difference between group A and group B. The global score of the modified BPI-7S increased by 8.5 (± 12.8) points (from 34.7 ± 13.6 at the beginning to 26.2 ± 15.8 at the end of treatment), from which a statistically significant improvement in the quality of life of patients can be derived. Global patient contentment improved, most notably the rapid onset of 2.4 points to 3.4 points at the end of the study. 76.9% of patients found taking FBT simple or very simple.

Improved patient functioning after treatment of breakthrough cancer pain: an open-label study of fentanyl buccal tablet in patients with cancer pain.

PURPOSE: This open-label study evaluated the effects of fentanyl buccal tablet (FBT) on functioning and mood in cancer patients with breakthrough cancer pain (BTcP). METHODS: Opioid-tolerant patients in seven European countries with up to four BTcP episodes/day received FBT doses (100-800 µg) identified during open-label titration to treat up to eight BTcP episodes during an open-label treatment period. In countries where FBT was not commercially available, patients could enter an open-label continuation phase. Functionality and satisfaction assessments included change from baseline to the end of the treatment period in the modified Brief Pain Inventory (BPI-7S) seven-item interference subscale, patient's global assessment of satisfaction and ease of use, and Patient's Global Impression of Change (PGIC). Safety was also assessed. RESULTS: Of 330 randomized patients, 218 completed the treatment period and 88 entered the continuation phase. Median background pain intensity was 4.0 (mild) throughout the study. After the treatment period, mean (SD) global modified BPI-7S score improved from 39.7 (15.9) at baseline to 31.6 (16.8) for a mean change of -8.6 (95% confidence interval CI -10.5, -6.7; P < 0.0001), and 74.5% of patients reported improvement in overall status (PGIC) compared with 25.5% who reported no change or worsening (P < 0.001). Treatment-related adverse events (≥2 patients) during the continuation phase were application site erythema (6.9%), application site swelling (4.6%), and vertigo (4.6%). CONCLUSIONS: FBT may improve patient functioning, mood, and overall satisfaction in the management of BTcP. Long-term data did not indicate new safety concerns with FBT doses up to 800 µg.

[WINHO quality indicators for outpatient oncology care in Germany]. / WINHO-Qualitätsindikatoren für die ambulante onkologische Versorgung in Deutschland.

The aim of the WINHO indicators project is to describe and enhance the quality of outpatient oncology care in Germany with indicators. This paper deals with the development of a set of evidence- and consensus-based meaningful indicators to assess the quality of outpatient oncology care in Germany. These indicators are intended to be applied in assessments of quality of patient care in oncology practices, in quality reports and in peer-to-peer benchmarking. A set of 272 already existing indicators was identified through internet and literature searches. After redundancy reduction and addition of newly developed indicators for areas of ambulatory oncology care that were not yet covered, a preliminary set of 67 indicators was established. The further development of the indicator set was based on a modified version of the two-step RAND/UCLA expert evaluation method, which has been internationally established for developing quality indicator sets. The indicators were modified after the first round of ratings. After completing and assessing the second round of ratings, a set of 46 homogeneously positively rated quality indicators is now available for outpatient oncology care in Germany.

Malignant melanoma S3-guideline "diagnosis, therapy and follow-up of melanoma".

This first German evidence-based guideline for cutaneous melanoma was developed under the auspices of the German Dermatological Society (DDG) and the Dermatologic Cooperative Oncology Group (DeCOG) and funded by the German Guideline Program in Oncology. The recommendations are based on a systematic literature search, and on the consensus of 32 medical societies, working groups and patient representatives. This guideline contains recommendations concerning diagnosis, therapy and follow-up of melanoma. The diagnosis of primary melanoma based on clinical features and dermoscopic criteria. It is confirmed by histopathologic examination after complete excision with a small margin. For the staging of melanoma, the AJCC classification of 2009 is used. The definitive excision margins are 0.5 cm for in situ melanomas, 1 cm for melanomas with up to 2 mm tumor thickness and 2 cm for thicker melanomas, they are reached in a secondary excision. From 1 mm tumor thickness, sentinel lymph node biopsy is recommended. For stages II and III, adjuvant therapy with interferon-alpha should be considered after careful analysis of the benefits and possible risks. In the stage of locoregional metastasis surgical treatment with complete lymphadenectomy is the treatment of choice. In the presence of distant metastasis mutational screening should be performed for BRAF mutation, and eventually for CKIT and NRAS mutations. In the presence of mutations in case of inoperable metastases targeted therapies should be applied. Furthermore, in addition to standard chemotherapies, new immunotherapies such as the CTLA-4 antibody ipilimumab are available. Regular follow-up examinations are recommended for a period of 10 years, with an intensified schedule for the first three years.

Adjuvant therapy reduces the benefit of palliative treatment in disseminated breast cancer - own findings and review of the literature.

BACKGROUND: Adjuvant treatment concepts have improved the 10-year cure rate of breast and colon cancer, but new treatments for metastatic disease have yielded only incremental benefit. If treatments for disseminated cancer were actually prolonging life rather than only increasing remission rates, this effect should have been documented over the last 30+ years. However, published data concerning advances in treatment for disseminated cancer have been contradictory. PATIENTS AND METHODS: To add data-based information, we analyzed 2 sources: a regional population-based cancer registry (Hamburgisches Krebsregister, HKR), and a research cancer registry (Projektgruppe Internistische Onkologie, PIO). We compared the survival of several thousand patients with metastatic disease who received treatment only after dissemination with that of patients who received initial adjuvant therapy. RESULTS: After adjuvant treatment, survival in patients with disseminated breast cancer is up to a third shorter than that of patients without adjuvant therapy. CONCLUSIONS: In accordance with published evidence, we conclude that ineffective adjuvant treatment shortens survival after documentation of metastatic disease. This is probably due to the elimination of chemo-sensitive tumor cells or to the induction of resistance in remaining micrometatases. This negative effect on survival after dissemination has been shown clearly for breast cancer and is also probable for cancer of the colon and other sites.

Superior outcome of women with stage I/II cutaneous melanoma: pooled analysis of four European Organisation for Research and Treatment of Cancer phase III trials.

PURPOSE: Several studies observed a female advantage in the prognosis of cutaneous melanoma, for which behavioral factors or an underlying biologic mechanism might be responsible. Using complete and reliable follow-up data from four phase III trials of the European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group, we explored the female advantage across multiple end points and in relation to other important prognostic indicators. PATIENTS AND METHODS: Patients diagnosed with localized melanoma were included in EORTC adjuvant treatment trials 18832, 18871, 18952, and 18961 and randomly assigned during the period of 1984 to 2005. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs for women compared with men, adjusted for age, Breslow thickness, body site, ulceration, performed lymph node dissection, and treatment. RESULTS: A total of 2,672 patients with stage I/II melanoma were included. Women had a highly consistent and independent advantage in overall survival (adjusted HR, 0.70; 95% CI, 0.59 to 0.83), disease-specific survival (adjusted HR, 0.74; 95% CI, 0.62 to 0.88), time to lymph node metastasis (adjusted HR, 0.70; 95% CI, 0.51 to 0.96), and time to distant metastasis (adjusted HR, 0.69; 95% CI, 0.59 to 0.81). Subgroup analysis showed that the female advantage was consistent across all prognostic subgroups (with the possible exception of head and neck melanomas) and in pre- and postmenopausal age groups. CONCLUSION: Women have a consistent and independent relative advantage in all aspects of the progression of localized melanoma of approximately 30%, most likely caused by an underlying biologic sex difference.

Fentanyl buccal tablet for breakthrough cancer pain: why titrate?

Breakthrough cancer pain is a significant problem for many patients with cancer because of the fast onset and often unpredictable nature of the pain episodes. The rapid onset opioids therefore have a central role to play in the management of breakthrough cancer pain. The rapid onset opioid fentanyl buccal tablet provides a fast analgesic effect and is easy to administer. However, titration of the medication is essential in order to optimize the management of pain. This is because individual patient characteristics, comorbidities, and other treatments may influence the absorption, pharmacokinetics, and pharmacodynamics of drugs. It is therefore important to individualize treatment by determining the effective dose for each patient, which is the dose that provides adequate analgesia and minimizes undesirable adverse effects. Data from clinical studies of fentanyl buccal tablet show that patients' effective doses ranged from 100 to 800 µg per episode, highlighting the need for the titration process. Following successful dose titration, treatment with fentanyl buccal tablet can achieve significant pain relief as early as 10 minutes after administration, resulting in a high level of patient satisfaction.

Frequency of side effects in outpatient cancer care and their influence on patient satisfaction--a prospective survey using the PASQOC questionnaire.

STUDY OBJECTIVES: The aims of the study were to examine the frequency of side effects and fatigue in ambulatory cancer patients and to analyse how these symptoms are reflected in patient satisfaction. SETTING: Private practices (N = 41) and day hospitals (N = 8) in Germany took part in the study. PARTICIPANTS: The respondents were 4,538 patients with cancer (response rate: 82%). The diagnoses were: 25% breast cancer, 21% colorectal cancer, 11% lymphomas and 12% haematological malignancies; mean age 63.5 years; 57% female. MEASUREMENTS: The 2004 PASQOC questionnaire contained 63 problem-oriented items which covered patient satisfaction for 15 dimensions of care. One item specifically assessed the prevalence of 17 different side effects. A score reflecting the severity of fatigue (fatigue index) was computed from three additional questions. For statistical analysis of patient satisfaction, the problem frequency was computed for each item. RESULTS: The most frequent single side effects were fatigue (60%), hair loss (54%), nausea (51%), sleep disturbance (42%), weight loss (36%), diarrhoea (32%) and mouth ulcerations (31%). The mean number of side effects was 5 per patient (range 0 to 17). The fatigue index revealed that 42% of subjects complained of moderate and 28% of severe fatigue. Both the total number of side effects and the fatigue score were negatively associated with patient satisfaction. CONCLUSIONS: Side effects and especially fatigue are frequent problems in cancer patients and are related to the patients' assessment of cancer care. Routine symptom assessment may identify patients who require more comprehensive supportive care.

Patient satisfaction in outpatient cancer care: a prospective survey using The PASQOC questionnaire.

STUDY OBJECTIVES: To examine how outpatient cancer patients assess their cancer care in private oncology practices and day hospitals, and to identify the extent to which staff meet the expectations of their patients. SETTING: Private practices (n = 41) and day hospitals (n = 8) in Germany, including 16 "repeater" practices who had already participated in the 2002 Patient Satisfaction and Quality in Oncological Care (PASQOC) survey. PARTICIPANTS: n = 4,615 patients with cancer. Diagnoses: 25% breast cancer, 21% colorectal cancer, 12% haematologic malignancies, 11% lymphomas; mean age 63.5 years; 57% female; n = 1,639 patients from repeater practices. MEASUREMENTS: The 2004 PASQOC questionnaire contained 63 problem-oriented items which covered 15 different dimensions of care. Practice staff invited their patients to participate and surveys were mailed to all sampled patients. For statistical analysis, the problem frequency (PF) was calculated for each item. RESULTS: Of 5,600 patients who received the questionnaire, 4,615 replied (response rate: 82%). The best results were obtained for the dimensions "further support in daily life" (3% PF), "nurses" (5% PF), and "physician-patient-relationship" (8% PF). Potential for improvement was most pronounced for "handling of side effects" (39% PF), "partnership and shared decision making" (30% PF), "side effects" (30% PF) and "communication with other patients" (26% PF). Considerable differences in PFs between practices were observed. Mean results from the 16 repeater practices revealed only few changes compared to the 2002 PASQOC survey, although some practices had greatly improved their performance. CONCLUSIONS: The PASQOC questionnaire identified strengths and weaknesses of outpatient care for cancer patients. By providing a comparison with other practices, PASQOC can help staff of individual practices to improve their performance.

Costs of treatment of colorectal cancer in different settings in Germany.

The objective of this study was to evaluate the cost implications of different settings (inpatient, outpatient/day clinic, or office-based oncologists) for the administration of standard fluoropyrimidine therapies, i.e., Mayo Clinic and Arbeitsgemeinschaft Internistische Onkologie (AIO)/Ardalan regimen, and to compare the results with the cost of oral capecitabine in Germany. In total, 89 quarterly fee-listings from 26 patients provided by 5 office-based oncologists were analyzed. Physician's services, drug costs, pharmacy costs, and costs for implantable venous port systems and single-use pumps were considered. Findings were transferred to the hospital setting. A third-party payer perspective was applied. Quarterly treatment costs for the Mayo Clinic regimen varied between 2,036 and 10,569, and between 1,294 and 10,179 for the AIO/Ardalan regimen depending on the treatment setting. Projected costs for capecitabine were 2,338. No hospitalization was considered to be necessary for capecitabine due to its oral administration route. The most expensive treatment options were the AIO/Ardalan protocol in the office-based setting and the Mayo Clinic protocol in the hospital setting. Capecitabine emerged as the cheapest option in the office-based setting. Overall, the cheapest option was the AIO/Ardalan protocol in municipal hospitals. However, municipal hospitals are unlikely to cover their costs in this situation. Substantial cost savings without incurring losses to providers may be realized if patients are transferred from the hospital setting to the office-based setting and treated with capecitabine.

Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women: a prospective combined analysis of two multicenter trials.

BACKGROUND: Fulvestrant (ICI 182,780) is a new type of estrogen receptor (ER) antagonist that down-regulates the ER and has no known agonist effects. The authors report the prospectively planned combined analysis of data from 2 Phase III trials comparing fulvestrant 250 mg monthly (n=428) and anastrozole 1 mg daily (n=423) in postmenopausal women with advanced breast carcinoma (ABC) who previously had progressed after receiving endocrine treatment. METHODS: The primary endpoint was time to progression (TTP). Secondary endpoints included objective response (OR), duration of response (DOR), and tolerability. The trials were designed to demonstrate superiority of fulvestrant over anastrozole. Noninferiority of fulvestrant versus anastrozole was determined using a retrospectively applied statistical test. RESULTS: At a median follow-up of 15.1 months, approximately 83% of patients in each treatment arm had progressed. The median TTP was 5.5 months in the fulvestrant group and 4.1 months in the anastrozole group, and the OR rates were 19.2% and 16.5% for fulvestrant and anastrozole, respectively (although the difference between treatments was not statistically significant). In patients who responded, further follow-up (median, 22.1 months) was performed to obtain more complete information on DOR; the median DOR (from randomization to disease progression) in patients who responded to treatment was 16.7 months in the fulvestrant group and 13.7 months in the anastrozole group. In a statistical analysis of DOR (using all randomized patients; from the start of response to disease progression), DOR was significantly longer for patients in the fulvestrant group compared with patients in the anastrozole group. Both drugs were tolerated well; withdrawals due to drug-related adverse events were 0.9% and 1.2% in the fulvestrant group and the anastrozole group, respectively. The incidence of joint disorders was significantly lower in the fulvestrant group (P=0.0036). CONCLUSIONS: Fulvestrant was tolerated well and was at least as effective as anastrozole in the second-line treatment of patients with ABC. This new hormonaltherapy may provide a valuable treatment option for ABC in postmenopausal women.

Inverse association between melanoma and previous vaccinations against tuberculosis and smallpox: results of the FEBIM study.

Various forms of immunotherapy utilizing bacille Calmette-Guérin vaccine or vaccinia vaccine have been evaluated in clinical trials on melanoma patients. The effect of the "natural" application of these vaccinations, administered to provide protection against tuberculosis and smallpox, has, however, never been studied in epidemiologic investigations on risk factors for melanoma. In a case-control study comprising 11 institutions in seven countries we recruited 603 incident melanoma cases and 627 population controls frequency matched to the cases with respect to sex, age, and ethnic origin within each center to assess this relationship to obtain insights into the prevention of melanoma. Exposure information, incorporating also detailed ascertainment of potential confounding variables, was obtained in standardized personal interviews at the study subject's home. We found an inverse association between melanoma risk and previous bacille Calmette-Guérin vaccine/vaccinia vaccination depicted by an adjusted odds ratio of 0.44 (95% confidence interval: 0.26-0.72) for those vaccinated against tuberculosis and smallpox compared with subjects without a positive history of either vaccination. A variety of subgroup analyses showing a consistent pattern of results make it unlikely that the observed inverse association is a spurious finding. We conclude that bacille Calmette-Guérin vaccination and vaccinia vaccination may lower melanoma risk. Current immunologic theory of melanoma development provides a sound basis for understanding the biologic plausibility of the findings that have to be confirmed in future studies.