Routine Clinical Practice In Germany Research Articles

Efficacy and Tolerability of Leuprorelin Acetate (Eligard®) in Daily Practice in Germany: Pooled Data from 2 Prospective, Non-Interventional Studies with 3- or 6-Month Depot Formulations in Patients with Advanced Prostate Cancer

Introduction: We evaluated the efficacy and tolerability of 3- and 6-month leuprorelin acetate (LA) depot formulations (Eligard®, Astellas Pharma GmbH) in patients with advanced prostate cancer treated in routine clinical practice in Germany. Materials and Methods: Data was pooled from 2 prospective, open-label, non-interventional studies in which 1,906 patients were treated for 12 months with either the 3-month (n = 633) or 6-month (n = 1,273) LA formulation. Results: Median prostate-specific antigen levels in the pooled patient population declined from 12.0 ng/mL at baseline to 0.5 ng/mL after 12 months. Prostate-specific antigen reduction was achieved in treatment-naïve and pre-treated patients. Adverse events were documented in 8.8% of patients. Conclusions: These pooled data from routine clinical practice in Germany indicate that LA 3- and 6-month depot injections can effectively reduce prostate-specific antigen levels in a broad patient population with advanced prostate cancer.

Aflibercept for Patients with Neovascular Age-Related Macular Degeneration in Routine Clinical Practice in Germany: Twelve-Month Outcomes of PERSEUS

To explore real-world effectiveness of intravitreal aflibercept injection (IAI) for neovascular age-related macular degeneration (nAMD) in Germany. A 24-month, prospective, noninterventional, noncontrolled, multicenter observational cohort study. Patients (n= 848) with nAMD treated with IAI. Patients (n= 988) were screened at 67 study sites. Therapeutic decisions were made by the treating physician. Primary end point analysis was performed after 12 months for the entire study cohort and for predetermined subgroups of treatment-naïve and previously treated patients. Additionally, outcomes with regular injection intervals (bimonthly after 3 monthly injections) were compared with those of patients with irregularities in their treatment regimen. The primary end point was the mean change in visual acuity (VA) from baseline after 12 months. Other key end points included the proportions of patients gaining 15 letters or more and patients with reading vision (≥70 letters). Furthermore, the number of injections, anatomic measurements, and safety data were recorded. Mean ± standard deviation VA improvement was 5.3±17.4 letters in treatment-naïve patients and-0.1±15.6 letters in previously treated patients (P ≤ 0.0001), and that of the total study group was 2.9±16.8 letters. Baseline VA was 53.4±17.9 letters for treatment-naïve patients, 52.9±18.4 letters for previously treated patients, and 53.2±18.1 letters for the total patient population. Treatment pattern was associated with VA outcome: best outcomes-an average VA gain of 8.0±17.7 letters-were seen in treatment-naïve patients in the regularly treated population, whereas irregularly treated, treatment-naïve patients achieved a mean VA gain of only 4.0±17.1 letters. Among previously treated patients, regular treatment also was associated with better outcomes (+3.1±10.7 vs.-1.1±16.8 letters). For the total study group, the mean VA gain was the following: regularly treated population, 6.1±15.6 letters; irregularly treated population, 1.5±17.1 letters (P= 0.008). No cases of endophthalmitis were observed during the first 12 months of the study. Adverse events were in line with the known safety profile of IAI. After 12 months of treatment with IAI, treatment-naïve patients showed substantial functional benefit, whereas previously treated patients maintained their VA. With regular IAI treatment, it seems that similar results as those in pivotal IAI studies can be achieved in routine clinical practice.

Patients’ perception of Parkinson’s disease-associated pain following initiation of rotigotine: a multicenter non-interventional study

ABSTRACTObjectives: To evaluate Parkinson’s disease (PD)-associated pain as perceived by the patients (subjective characterization), and how this may change following initiation of rotigotine transdermal patch.Methods: SP1058 was a non-interventional study conducted in routine clinical practice in Germany and Austria in patients experiencing PD-associated pain (per the physician’s assessment). Data were collected at baseline (ie, before rotigotine initiation) and at a routine visit after ≥25 days (–3 days allowed) of treatment on a maintenance dose of rotigotine (end of study [EoS]). Pain perception was assessed using the 12-item Pain Description List of the validated German Pain Questionnaire (each item ranked 0 = ‘not true’ to 3 = ‘very true’). Primary effectiveness variable: change from baseline to EoS in the sum score of the 4 ‘affective dimension’ items of the Pain Description List. Secondary effectiveness variables: change from baseline to EoS in Unified Parkinson’s Disease Rating Scale (UPDRS) II, III, and II+III scores, and Parkinson’s Disease Questionnaire (PDQ-8) total score (PD-related quality-of-life). Other variables included scores of the eight ‘sensory dimension’ items of the Pain Description List.Results: Of 93 enrolled patients (mean [SD] age: 71.1 [9.0] years; male: 48 [52%]), 77 (83%) completed the study, and 70 comprised the full analysis set. The mean (SD) change from baseline in the sum score of the four ‘affective dimension’ items was –1.3 (2.8) indicating a numerical improvement (baseline: 3.9 [3.4]). In the ‘sensory dimension’, pain was mostly perceived as ‘pulling’ at baseline (49/70 [70%]); ‘largely true’/‘very true’). Numerical improvements were observed in all UPDRS scores (mean [SD] change in UPDRS II+III: −5.3 [10.5]; baseline: 36.0 [15.9]), and in PDQ-8 total score (−2.0 [4.8]; baseline: 10.7 [5.9]). Adverse drug reactions were consistent with dopaminergic stimulation and transdermal administration.Conclusion: The perception of the ‘affective dimension’ of PD-associated pain numerically improved in patients treated with rotigotine. ClinicalTrials.gov identifier: NCT01606670; https://clinicaltrials.gov/ct2/show/NCT01606670?term=NCT01606670&rank=1

Similar efficacy and tolerability of raltegravir-based antiretroviral therapy in HIV-infected patients, irrespective of age group, burden of comorbidities and concomitant medication: Real-life analysis of the German 'WIP' cohort.

Only limited efficacy and tolerability data on raltegravir (RAL) use are currently available. Study objectives were to describe the efficacy and tolerability profile of RAL-based antiretroviral therapy (ART) in routine clinical practice in Germany. The WIP study (WIP = “Wirksamkeit von Isentress unter Praxisbedingungen”, Efficacy of Isentress under routine clinical conditions) was a prospective, multi-centre cohort study in Germany. Human immunodeficiency virus (HIV)-infected patients aged ≥ 18 years in whom combinational ART with RAL 400 mg BID was indicated were enrolled. The primary endpoint was virologic response (HIV-RNA <50 copies/mL; non-completion equals failure) after 48 weeks. Of 451 patients, 85.1% (n = 384) were still receiving RAL at week 48. At baseline (BL), the prevalence of concomitant diseases was higher in patients of the age group ≥50 years (94.2% vs. 75.7%) as well as concomitant medications (74.8 % vs. 55.4%). Virologic response at week 48 was 74.7% (overall), 75.0% (naïve at BL), 81.5% (suppressed at BL), 47.1% (interrupted previous treatment at BL) and 64.9% (failing at BL), without significant differences by age group. A significant correlation of achievement of HIV-RNA <50 copies/mL was seen with treatment status at BL (p = 0.004). In addition, 77.3 % of the patients with a CD4 cell count >200 cells/µL at BL achieved HIV-RNA <50 copies/mL (p = 0.029). RAL was well tolerated with 80 adverse events (AEs) in 49 patients (10.9%) and 8 serious AEs (SAEs) in 6 patients (1.3%) reported to be drug related. A total of 22 patients (4.9%) discontinued treatment due to AEs. The WIP study shows that the previously reported efficacy and safety profile of RAL can be achieved in a population with multiple comorbidities and comedications, with no major difference observed in ageing patients (≥50 years) vs. younger patients. RAL is therefore an attractive treatment option in routine medical care in Germany.

Optimised photodynamic diagnosis for transurethral resection of the bladder (TURB) in German clinical practice: results of the noninterventional study OPTIC III

PurposeWhite light cystoscopy (WLC) is the standard procedure for visualising non-muscle invasive bladder cancer (NMIBC). However, WLC can fail to detect all cancerous lesions, and outcomes with transurethral resection of the bladder differ between institutions, controlled trials, and possibly between trials and routine application. This noninterventional study assessed the benefit of hexaminolevulinate blue light cystoscopy (HALC; Hexvix®, Ipsen Pharma GmbH, Germany) plus WLC versus WLC alone in routine use.MethodsFrom May 2013 to April 2014, 403 patients with suspected NMIBC were screened from 30 German centres to perform an unprecedented detailed assessment of the additional detection of cancer lesions with HALC versus WLC alone.ResultsAmong the histological results for 929 biopsy samples, 94.3 % were obtained from suspected cancerous lesions under either WLC or HALC: 59.5 % were carcinoma tissue and 40.5 % were non-cancerous tissue. Of all cancer lesions, 62.2 % were staged as Ta, 20.1 % as T1, 9.3 % as T2, 7.3 % as carcinoma in situ (CIS), and 1.2 % were unknown. Additional cancer lesions (+6.8 %) and CIS lesions (+25 %, p < 0.0001) were detected by HALC plus WLC versus WLC alone. In 10.0 % of patients, ≥1 additional positive lesion was detected with HALC, and 2.2 % of NMIBC patients would have been missed with WLC alone. No adverse events were observed.ConclusionsThe results of this study demonstrate that HALC significantly improves the detection of NMIBC versus WLC alone in routine clinical practice in Germany. While this benefit is statistically significant across all types of NMIBC, it seems most relevant in CIS.

3106 Open label, multicenter, prospective non-interventional study to monitor the safety and effectiveness of Bevacizumab with chemotherapy in patients with NSCLC under conditions of routine clinical practice in Germany

3106 Open label, multicenter, prospective non-interventional study to monitor the safety and effectiveness of Bevacizumab with chemotherapy in patients with NSCLC under conditions of routine clinical practice in Germany

Prevention and Treatment of Chemotherapy-Induced Neutropenia with the Biosimilar Filgrastim: A Non-Interventional Observational Study of Clinical Practice Patterns

Background: Biosimilars are similar but non-identical versions of existing biological drugs. The HEXAFIL study was an observational study that assessed the clinical usage, safety and efficacy of the biosimilar filgrastim in routine clinical practice in Germany. Patients and Methods: A total of 1,337 cancer patients received the biosimilar filgrastim for primary prophylaxis (PP), secondary prophylaxis (SP) or interventional treatment (TX) plus chemotherapy. Data including neutropenic complications and adverse events (AEs) were documented for up to 3 consecutive cycles. Results: In cycle 1, 44.9% of the patients received the biosimilar filgrastim as PP, 31.0% as SP, and 23.6% as TX. Approximately 90% of the patients required no modifications to their chemotherapy regimen, with lower rates among the PP/SP versus the TX patients. Neutropenic complications occurred in 7.9%, 6.9%, and 3.9% of the patients (cycles 1, 2, and 3, respectively). Only 1.8% of the patients experienced febrile neutropenia during cycle 1. Earlier and longer filgrastim treatment reduced grade 3/4 leukopenia and neutropenic complications. The observed safety/tolerability profile was as expected; the most common AE (4.3%) was musculoskeletal back/bone pain. Conclusion: In this observational real-life study of clinical practice, the biosimilar filgrastim was effective and well tolerated, with results consistent with those reported in phase II and phase III trials.

Caregivers’ and physicians’ attitudes to rotigotine transdermal patch versus oral Parkinson’s disease medication: an observational study

Objective:To provide real-world data on caregiver and physician perceptions of the advantages and disadvantages of rotigotine transdermal patch (Neupro) versus oral Parkinson’s Disease (PD) medication.Methods:Cross-sectional, non-interventional study in routine clinical practice in Germany (NCT01330290). Patients had PD with documented need for care, and had received rotigotine transdermal patch as add-on to oral PD treatment for ≥1 month. Caregivers/nurses and physicians assessed rotigotine transdermal patch versus oral PD medications using questionnaires. Specific questions regarding the possible benefits of transdermal application were asked and comprised questions on: swallowing dysfunction, nausea/vomiting, monitoring therapy, once daily application, application independently from meals, application to sleeping patients, caregiving efforts (caregivers only) and clinical aspects (physicians only). Each question was assessed on a 5 point scale ranging from -2 (major disadvantage) to 2 (major advantage) compared with oral treatment. Primary outcomes were mean total scores of all questions for caregivers/nurses and physicians who provided responses for ≥4 questions. As there are no validated tools to assess physician/caregiver preference in the PD setting, there is no reference against which the current findings can be compared; this study serves to pilot the questionnaires.Results:Questionnaire responses from 128 caregivers/nurses and 41 physicians were documented for 147 patients. One hundred (68%) patients had a caregiving family member; 40 (27%) were cared for by a nurse. Mean PD duration was 8.2 (SD 6.3) years; 136 (93%) patients were taking levodopa. Mean total score of caregivers’/nurses’ questionnaires was 1.32 (SD 0.67) and of physicians’ questionnaires was 1.46 (0.32) indicating a perceived advantage of rotigotine transdermal patch over oral PD therapy. Mean scores for individual questions were in the range 1.03–1.54 for caregivers/nurses and 1.15–1.87 for physicians. When given a choice about rationale to prescribe, physicians cited pharmaceutical form (patch) in 139 (95%) cases and active agent (rotigotine) in 89 (61%) cases.Conclusion:Caregivers/nurses and physicians perceived advantages with rotigotine transdermal patch compared to an oral PD medication as add-on therapy in patients with PD; advantages were observed in aspects of medical treatment as well as in everyday situations of caregiving of PD patients.

Tapentadol Prolonged Release as Used in Clinical Practice in Patients with Severe Chronic Tumor Pain

Objective: This subgroup analysis of a non-interventional study that included general practitioners and internists, assessed efficacy and safety of tapentadol prolonged release (Palexia® retard) as used in routine clinical practice in Germany for the treatment of severe chronic tumor pain. Study design: Data of all patients in the study cohort who were exclusively diagnosed with ‘tumor pain’ (n=143) were included in this analysis. Data collection during the 3-month observation period included previous analgesic and concomitant treatment, tapentadol PR dosage, pain intensity, sleep and quality of life parameters and tolerability of tapentadol PR. Results: A total of 96.5% of all patients with tumor pain had already received analgesic long-term treatment before initiation of tapentadol PR therapy, 49.0% of those had received strong opioids. Switching to tapentadol PR resulted in a mean pain reduction of 3.8 points from 7.1 ± 1.4 at baseline to 3.3 ± 1.9 at end of observation (NRS-11, 11-point pain scale; descriptive p value 50%, and 89.9% of the patients attained either their desired pain reduction and/or an additional individual treatment goal; both goals had been predefined at start of tapentadol PR treatment. This was accompanied by a significant decrease in pain-related impairments of daily activities and an improvement in quality of life (descriptive p value<0.001) with an overall good tolerability of tapentadol PR. Treatment with tapentadol PR was assessed positively by physicians and patients. Conclusions: In this routine clinical practice non-interventional study, treatment with tapentadol PR resulted in effective and well-tolerated relief of severe tumor pain and improvement of pain-related impairments of daily activities and quality of life. Tapentadol PR, an innovative effective analgesic, may thus provide an alternative treatment option in the management of tumor pain.

Panitumumab (pmab) in patients (pts) with chemorefractory metastatic colorectal cancer (mCRC): Final analysis from a community-based, observational study (VECTOR) in Germany.

550 Background: Pmab monotherapy significantly improves progression-free survival versus best supportive care in pts with chemorefractory KRAS wild-type (WT) mCRC. This study evaluated the efficacy and safety of pmab in routine clinical practice in Germany. Methods: To ensure a representative sample, eligibility criteria were largely unrestricted. Consenting pts were &gt;18 years old, had histologically confirmed KRAS WT mCRC, &gt;4 weeks pmab therapy, failure of fluoropyrimidine-, oxaliplatin- and irinotecan-containing chemotherapy (CTx) regimens, and women of child-bearing age received contraception. Predefined endpoints were overall response rate (ORR; investigator`s assessment) and skin toxicity (NCI Common Terminology Criteria for Adverse Events v3.0). Results: A total of 428 pts were included in the full analysis set. At the start of pmab therapy, median age was 69 (range 22-89) years, 268 pts (63%) were male and 343 (80%) had an ECOG performance status of 0-1. Overall, 400 pts (93%) had undergone prior surgery and 154 (36%) had received ≥1 cycle of adjuvant CTx. Pts had received a median of 3 cycles (range: 1‑12) of prior CTx for mCRC. The most common regimens were FOLFOX/FOLFIRI ±antibody therapy; 65% of regimens were given with palliative, 32% with curative/palliative and 3% with curative intent. The median pmab dose was 6 mg/kg (range 2.4-7.2) q2w for a median of 8 (range 2‑45) cycles, with 143 pts (33%) receiving &gt;10 cycles. The ORR during pmab therapy was 20% (complete response: n=7 [2%]; partial response: n=77 [18%]); disease control (including stable disease) was achieved in 261 pts (61%). Skin reactions occurred in 324 pts (67%) with 52% experiencing a maximum grade ≥2. Most pts had some type of rash (48% acne, 5% desquamation, 4% hand-foot skin reaction, 1% erythema multiforme). Overall, 21% of pts had other toxicities. Three serious adverse drug reactions (infection/fever; thrombosis/embolism; erythema multiforme) and two grade 1 infusion reactions were reported. Conclusions: In this observational study, pmab monotherapy had efficacy at least as good as was seen in the randomised pmab trial and safety was also similar.

STRike ‐ characteristics of HIV‐1‐infected patients treated with a single‐tablet regimen in daily clinical practice

The life‐long antiretroviral treatment of HIV‐1 infection requires effective and well tolerated medications complemented by high rates of adherence in order to achieve viral suppression, immunologic reconstitution and to prevent the development of resistance. Single‐tablet regimens (STRs), combining a full antiretroviral regimen in one tablet taken once daily, have been designed to achieve high adherence and better long‐term outcomes. “STRike” is the first cohort study, describing the use of various STRs in routine clinical practice in Germany. In this observational cohort study 800 participants will be included in 4 treatment arms, treated with the STRs of TDF/FTC/EFV (a retrospective and prospective arm), TDF/FTC/RPV or TDF/FTC/COBI/EVG after regulatory approval. Patients are followed for at least two years, and reasons for choice of medications and treatment satisfaction will be collected, in addition to safety, demographic, effectiveness data. To date 344 patients on TDF/FTC/EFV and 123 patients on TDF/FTC/RPV are being followed. In general, the spectrum of patients in the study reflects the German HIV‐1 infected population with regards to gender (88%/89% male), age (median 40/38 years of age) and mode of infection (71%/63% MSM). However, patients starting TDF/FTC/RPV are less progressed in their disease according to their CDC stage compared with patients on TDF/FTC/EFV (74.5% stage “A” vs. 53.2%). Patients starting TDF/FTC/RPV show less comorbidities (54% vs. 82%) with a spectrum different from patients on TDF/FTC/EFV. Pre‐existing neuropsychiatric comorbidities are relatively more common (10% more) among patients starting TDF/FTC/RPV than TDF/FTC/EFV. The decision to use an STR is mostly driven by patient preference to start with a more convenient ART regimen (56%) or to simplify their current ART regimen (75%). STRs aim to make treatment of HIV more convenient, more efficacious and more durable and by that allowing for earlier initiation of treatment. Different STRs may meet the requirements of distinct patient populations. TDF/FTC/RPV in this early review of our data, is utilized by younger patients with fewer overall comorbidities, but is selected more frequently for patients with pre‐existing neuropsychiatric comorbidities presumably to avoid the known neuropsychiatric complications of TDF/FTC/EFV. TDF/FTC/RPV appears to fit into the concept of early HIV treatment initiation as recommended by national and international guidelines.image

Urinary proteome analysis for prostate cancer diagnosis: Cost‐effective application in routine clinical practice in Germany

Capillary electrophoresis mass spectrometry urinary proteome analysis for prostate cancer has been shown to be highly accurate in the detection of prostate cancer. The aim of the present study was to report our experience with routine application of this test in clinical practice and its cost-effectiveness. The urinary proteome analysis for prostate cancer test was carried out in 211 patients in outpatient centers. In 184 of them, data about their follow up and the test results were available for analysis. Prostate cancer was detected in 49 cases. The test correctly recognized 42 out of 49 tumor patients, showing a sensitivity of 86% (95% confidence interval 73-94). Of 135 prostate cancer-negative patients, 79 had a negative urinary proteome analysis for prostate cancer test (specificity 59% [79/135 95% confidence interval 50-66]). Negative and positive predictive values were 92% (95% confidence interval 84-96) and 43% (95% confidence interval 33-53), respectively. A statistically significant (P<0.0005) improvement in terms of diagnostic accuracy was observed in comparison with serum prostate-specific antigen and percent-free prostate-specific antigen. Whereas the urinary proteome analysis for prostate cancer test results agreed in 65.7% with follow-up reference results, prostate-specific antigen achieved 33.3% and percent-free prostate-specific antigen achieved 42.7%. Cost-effectiveness analysis showed that the urinary proteome analysis for prostate cancer strategy outperformed the biopsy approach as well as prostate-specific antigen tests. The non-invasive urinary proteome analysis for prostate cancer test appears to be a helpful addition to prostate cancer diagnostics for patients with suspicious prostate-specific antigen and/or digital-rectal examination.

Capecitabine (X) in the first-line treatment of metastatic breast cancer (MBC).

1080 Background: The utility of anthracyclines/taxanes in MBC is decreasing as their use in EBC increases. Alternative agents are needed for treatment-resistant/-refractory pts presenting in the first-line MBC setting. We evaluate evidence for X as a first-line therapy. Methods: We reviewed data from phase II/III randomized trials and observational cohorts. Results: Significantly prolonged OS (p=0.02) was seen with first-line X 1,000mg/m2 bid vs CMF (tTable); in the X arm 40% of pts received therapy for >6 months and 18% for >1 year vs 21% and 5% of pts in the CMF arm. First-line X 1,250mg/m2 bid showed comparable efficacy (p=ns) to pegylated liposomal doxorubicin (PLD). In the SO14999 study (O’Shaughnessy JCO 2002), X 1,250mg/m2 bid + docetaxel (T) gave an ORR of 42% vs 31% for T in 169 pts receiving first-line therapy; ORR + SD rates were 82% and 72%. In combination with biologics, first-line X 1,000mg/m2 bid + bevacizumab (X-A; HR for PFS 0.69; p=0.0002) or sorafenib (X-S) (PFS, p=0.002) showed superior efficacy to X + placebo (X-pl). Results in the control arm of these studies were consistent with other studies of X monotherapy. First-line X 1,000mg/m2 bid was also effective in the single-arm, phase II MONICA study. Across the phase II/III trials, X was associated with minimal myelosuppression and alopecia, with hand-foot syndrome and diarrhea the most frequently reported grade 3/4 AEs. Results from observational studies in MBC pts receiving first-line X in routine clinical practice in Germany and France (n=479) confirmed the data reported in the interventional studies (Dalivoust SABCS 2010, Siedentopf Onkologie 2009). Conclusions: First-line X, often given at a dose of 1,000mg/m2 bid, is a well supported therapy in anthracycline-/taxane-pretreated MBC or in pts unsuited to taxanes, with proven efficacy and manageable safety in the first-line setting. Study Pts, n Median OS, months Median TTP/PFS, months ORR, % ANZBCTG0001 Stockler ASCO 2007 X vs CMF 214 vs 109 22.0 vs 18.0 6.0 vs 7.0 21.0 vs 18.0 PELICAN Jager ASCO 2010 X vs PLD 105 vs 105 29.4 vs 22.4 7.1 vs 6.2 24.4 vs 22.9 RIBBON-1 Robert ASCO 2009 X-A vs X-pl 409 vs 206 29.0 vs 21.2 8.6 vs 5.7 35.4 vs 23.6 SOLTI-0701 Baselga SABCS 2009 X-S vs X-pl 50 vs 62* – 7.6 vs 4.1 – MONICA Kaufmann EJC 2010 X 165 17.1 7.3 26.1 * First line only.

Capecitabine in the Routine Treatment of Advanced Breast Cancer: Results from a Non-Interventional Observational Study in 876 Patients

Background: This observational study evaluated patient characteristics, treatment schedule and setting, efficacy and tolerability of capecitabine in routine clinical practice in Germany. Patients and Methods: Patients with advanced breast cancer pretreated with or ineligible for anthracycline-containing therapy were treated with capecitabine. Data were collected until disease progression or completion of 12 cycles (with long-term follow-up in progression-free patients). Results: 846 of the 876 patients enrolled between 2002 and 2007 were eligible. Capecitabine was administered as monotherapy in 64% (median starting dose 1,070 mg/m² bis in diem (b.i.d.)) and combination chemotherapy (typically with vinorelbine or docetaxel) in 36% (median starting dose 987 mg/m2 b.i.d.). Capecitabine was given as first-line therapy in 35% of patients. Objective response rate was 41% and median progression-free survival was 7.5 months. Good performance status at baseline was a significant predictor of efficacy. The most common non-hematological toxicity was hand-foot syndrome (all grades: 54%; grade 3: 7%). Myelosuppression and alopecia were substantially less common with capecitabine monotherapy than with capecitabine combination regimens. Conclusions: Capecitabine, alone or in combination, is a feasible, effective treatment for breast cancer. Our findings in real-life clinical practice compare favorably with results from interventional studies, perhaps reflecting the longer treatment duration possible at more tolerable doses.

Capecitabine (X) in the routine treatment of advanced breast cancer (BC): Results from a large (n = 870) noninterventional study

e12021 Background: This observational study evaluated patient (pt) characteristics, treatment schedule and setting, efficacy and tolerability of X in routine clinical practice in Germany. Methods: Pts with advanced BC pretreated with or ineligible for anthracycline-containing therapy received X. As there was no specific protocol for X administration, data on dose, treatment duration, treatment delays/interruptions, and concomitant anticancer therapy were collected as well as efficacy data. Pts were followed until disease progression or completion of 12 cycles (with long-term follow-up in pts who were progression-free after 12 cycles). Results: Between 2002 and 2007, 870 pts were recruited from 135 centers, of whom 846 were eligible. Most pts (62%) were aged 50–69 years and 64% had received prior taxane therapy. X was given as monotherapy in 64% (median starting dose 1070 mg/m2 bid) and combination chemotherapy in 36% (median starting dose 987 mg/m2 bid), typically with vinorelbine or docetaxel. Generally, pts receiving X alone were slightly older and were more likely to have hormone receptor-positive disease than those receiving combination therapy. 35% of pts received X as first-line therapy. Pts received a median of 7 cycles; 26% received ≥12 cycles. Overall response rate (RR) was 41% (95% CI: 38–45) and median progression-free survival (PFS) was 7.5 months (95% CI: 7.1–8.3). RR was higher with combination therapy (49%) than monotherapy (37%), but PFS was similar in the two subgroups. Good performance status at baseline was a significant predictor of efficacy. The most common non-hematologic adverse event was hand-foot syndrome (all grades: 54%; grade 3: 7%), leading to premature treatment discontinuation in 6%. Myelosuppression and alopecia were substantially less common when X was administered as monotherapy than as combination chemotherapy. Conclusions: X, either alone or in combination, is a feasible and effective treatment for advanced BC. Our findings in real-life clinical practice compare favorably with results from interventional studies, perhaps reflecting the longer treatment duration possible at a more tolerable dose. No significant financial relationships to disclose.

Donepezil for Alzheimer’s Disease in Clinical Practice – The DONALD Study

This multicenter open-label clinical trial was designed to investigate the safety and efficacy of donepezil, a selective acetylcholinesterase inhibitor, in the treatment of Alzheimer’s disease (AD) in routine clinical practice in Germany. A total of 237 patients with mild-to-moderate AD were treated with donepezil for 24 weeks, 186 completed the study according to the protocol. In the completer group, mean MMSE score for efficacy showed an improvement from baseline of +1.6 points at week 12 (95% CI +1.1 to +2.1) and of +1.1 points at week 24 (95% CI +0.5 to +1.7). In more than 80% of the patients, global tolerability was rated to be very good or good. There were only insignificant effects on ECG parameters. This study confirms the results obtained in previous double-blind trials, which showed that donepezil is effective and well tolerated in patients with mild-to-moderately severe AD.

Stellenwert der Rektumexstirpation im Therapiekonzept des tief sitzenden Rektumkarzinoms

The main objective of surgery of rectal carcinomas is to avoid a permanent colostomy by sphincter-sparing surgical procedures. A variety of different abdominoperineal resection rates is described in the literature. The study was performed in 2000 within the framework of a multicentric study including 282 hospitals. The purpose of the study was to document the quality of diagnosis and therapy for colorectal carcinomas.A total of 9477 patients were included in this study: 3402 suffering from a rectal carcinoma and 6075 suffering from a colon carcinoma. A total of 866 abdominoperineal resections was performed. This corresponds to an abdominoperineal resection rate of 27.4%. In 30.4% of all men and in 23.0% of all women an abdominoperineal resection was performed. Of all tumor patients who underwent abdominoperineal resection, 8.3% had a pT4 carcinoma and 57.5% a pT3 carcinoma. Adapted to the localization of the tumor in the rectum, i.e., the distance of the aboral tumor margin to the anal verge, the following abdominoperineal resection rates were found: <4 cm from the anal verge 84.6%, 4-7.9 cm 43.9%, 8-11.9 cm 5.8%, and 12-16 cm 0.5%.Intraoperative complications occurred in 11.8%, specific postoperative complications in 33.1%, and general postoperative complications in 27.4% of the patients. The postoperative lethality was 2.8%. The mean postoperative hospital stay was 21.7 days. Logistic regression identified the body mass index, gender, the distance of the carcinoma from the anal verge, and the T category as independent factors influencing the abdominoperineal resection rate. Despite an overall decrease in use, abdominoperineal resection will continue to play an important role for the surgical treatment of low rectal cancers in routine clinical practice in Germany. It will remain an individual decision for each patient whether the tumor and the patient allow sphincter preservation or whether abdominoperineal resection seems to be necessary. According to the results of the present study,a general definition of an abdominoperineal resection rate in an unselected group of patients should be viewed critically.