Final results of a phase I/II pilot study of capecitabine with or without vinorelbine after sequential dose-dense epirubicin and paclitaxel in high-risk early breast cancer

Background: The integration of the non-cross-resistant chemotherapeutic agents capecitabine and vinorelbine into an intensified dose-dense sequential anthracycline- and taxane-containing regimen in high-risk early breast cancer (EBC) could improve efficacy, but this combination was not examined in this context so far. Methods: Patients with stage II/IIIA EBC (four or more positive lymph nodes) received post-operative intensified dose-dense sequential epirubicin (150mg/m2 every 2 weeks) and paclitaxel (225mg/m2 every 2 weeks) with filgrastim and darbepoetin alfa, followed by capecitabine alone (dose levels 1 and 3) or with vinorelbine (dose levels 2 and 4). Capecitabine was given on days 1-14 every 21 days at 1000 or 1250 mg/m2 twice daily (dose levels 1/2 and 3/4, respectively). Vinorelbine 25 mg/m2 was given on days 1 and 8 of each 21-day course (dose levels 2 and 4). Results: Fifty-one patients were treated. There was one dose-limiting toxicity (DLT) at dose level 1. At dose level 2 (capecitabine and vinorelbine), five of 10 patients experienced DLTs. Therefore evaluation of vinorelbine was abandoned and dose level 3 (capecitabine monotherapy) was expanded. Hand-foot syndrome and diarrhoea were dose limiting with capecitabine 1250 mg/m2 twice daily. At 35.2 months' median follow-up, the estimated 3-year relapse-free and overall survival rates were 82% and 91%, respectively. Administration of capecitabine monotherapy after sequential dose-dense epirubicin and paclitaxel is feasible in node-positive EBC, while the combination of capecitabine and vinorelbine as used here caused more DLTs. Trial registration: Current Controlled Trials ISRCTN38983527

Elektrocochleographische Muster bei Patienten mit auditorischer Neuropathie

Hintergrund: Die auditorische Neuropathie stellt ein Störungsbild dar, das sich klinisch und audiologisch mannigfaltig präsentieren kann. Bis heute sind die zugrundeliegenden physiologischen Mechanismen unklar. Jüngste Arbeiten deuten auf unterschiedlichen Erfolg einer CI-Versorgung bei Kindern mit ANP hin, abhängig vom Ort der zugrundeliegenden Schädigung.Ziel der vorliegenden Arbeit war es, bei Kindern mir einer auditorischen Neuropathie mit einer Elektrocochleographie am Promontorium den Ort der Läsion zu untersuchen und diese Ergebnisse mit klinisch-audiologischen und genetischen Daten zu korrelieren.Material und Methoden: Bei 14 von insgesamt 19 Kindern mit einer auditorischen Neuropathie erfolgte eine transtympanale Elektrocochleographie in Vollnarkose unter Verwendung von Clicks (0,1 ms Druck- und Sogimpulse in absteigender Intensität ab 100 dB mit einer Frequenz von 11,1 Impulsen pro sec) und Tonbursts im Frequenzbereich von 1000-4000 Hz. Desweiteren wurden bei 10 Kindern alle kodierenden Regionen der verschiedenen Otoferlinisoformen durch direkte Sequenzierung der Exons 1-48 sowie des 5`UTRsfl und des Introns, das sich zwischen 5`UTRsfl und dem Exon 20 befindet, untersucht.Ergebnisse: Die Schwelle der cochleären Mikrophonpotentiale lag bei 40 bis 60 dB. 11 Patienten zeigten ein Summationspotential mit/ oder ohne Summenaktionspotential. Bei 3 Kindern ließ sich ein langstreckiges negatives Potential nachweisen, wie mit einem dendritischen Potential vereinbar. Zwei Kinder zeigten Mutationen im Otoferlingen. Elektrocochleographisch wiesen beide Kinder ein perisynaptisches Schädigungsmuster auf. Ansonsten fand sich keine Korrelation zu klinisch audiologischen Daten.Diskussion: Die Elektrocochleographie ermöglicht es, den genauen Schädigungort bei Patienten mit ANP näher einzugrenzen. Dies könnte hilfreich sein, bei der Frage nach dem möglichen Erfolg vor CI-Implantation

West German Study PlanB Trial: Adjuvant Four Cycles of Epirubicin and Cyclophosphamide Plus Docetaxel Versus Six Cycles of Docetaxel and Cyclophosphamide in HER2-Negative Early Breast Cancer

PURPOSE The West German Study Group PlanB trial evaluated an anthracycline-free chemotherapy standard (six cycles of docetaxel and cyclophosphamide [TC]) in the routine treatment of human epidermal growth factor receptor 2-negative early breast cancer (EBC). PATIENTS AND METHODS Patients with pT1 to pT4c, all pN+, and pN0/high-risk EBC were eligible. High-risk pN0 was defined by one or more of the following: pT greater than 2, grade 2 to 3, high urokinase-type plasminogen activator/plasminogen activator inhibitor-1, hormone receptor (HR) negativity, and less than 35 years of age. After an early amendment, all HR-positive tumors underwent recurrence score (RS) testing, with chemotherapy omission recommended in RS less than or equal to 11 pN0 to pN1 disease. Patients were randomly assigned to four cycles of epirubicin (E)(90)/cyclophoshamide (C)(600) followed by four cycles of docetaxel (T)(100) or six cycles of T75C600 (administered once every 3 weeks). The primary end point was disease-free survival (DFS); secondary end points were overall survival (OS) and safety. The protocol specified P = .05 for a noninferiority margin of 4.4% for all patients combined. RESULT Of the 3,198 registered patients, 348 (RS <= 11) omitted chemotherapy, and 401 were not randomly assigned. The intention-to-treat population included 2,449 patients (1,227 EC-T v 1,222 TC: postmenopausal, 62.2% v60.8%; pNO, 58.2% v59.5%; pT1, 57.6% v52.3%; HR positive, 81.4% v82.2%; RS greater than 25 [in H.R-positive patients], 26.2% v 27.5%). Within the safety population (1,167 v 1,178 patients), 87.5% v 93.0% completed therapy. After a 60-month median follow-up, 5-year outcomes were similar in the EC-T and TC arms (DFS, 89.6% [95% CI, 87.9% to 91.5%] v89.9% [95% CI, 88.1% to 91.8%]; OS, 94.5% [95% CI, 93.1% to 95.9%] v94.7% [95% CI, 93.3% to 96.1%]). The DFS difference was within the noninferiority margin of the original trial design. Five treatment-related deaths were reported for TC (one for EC-T), despite a trend toward more-severe adverse events in the latter. Interaction analysis revealed no predictive trends with respect to key factors, including triple-negative, luminal A/B-like, pN, age, and RS status. CONCLUSION In the West German Study Group PlanB trial, 5-year outcomes for TC and EC-T were equally excellent. Six cycles of TC is an effective/safe option in human epidermal growth factor receptor 2-negative EBC with pN0 high genomic risk or pN1 EBC with genomically intermediate- to high-risk disease. (C) 2019 by American Society of Clinical Oncolog

Limited clinical relevance of imaging techniques in the follow-up of patients with advanced chronic lymphocytic leukemia: results of a meta-analysis

The clinical value of imaging is well established for the follow-up of many lymphoid malignancies but not for chronic lymphocytic leukemia (CLL). A meta-analysis was performed with the dataset of 3 German CLL Study Group phase 3 trials (CLL4, CLL5, and CLL8) that included 1372 patients receiving first-line therapy for CLL. Response as well as progression during follow-up was reassessed according to the National Cancer Institute Working Group1996 criteria. A total of 481 events were counted as progressive disease during treatment or follow-up. Of these, 372 progressions (77%) were detected by clinical symptoms or blood counts. Computed tomography (CT) scans or ultrasound were relevant in 44 and 29 cases (9% and 6%), respectively. The decision for relapse treatment was determined by CT scan or ultrasound results in only 2 of 176 patients (1%). CT scan results had an impact on the prognosis of patients in complete remission only after the administration of conventional chemotherapy but not after chemoimmunotherapy. In conclusion, physical examination and blood count remain the methods of choice for staging and clinical follow-up of patients with CLL as recommended by the International Workshop on Chronic Lymphocytic Leukemia 2008 guidelines. These trials are registered at http://www.isrctn.org as ISRCTN 75653261 and ISRCTN 36294212 and at http://www.clinicaltrials.gov as NCT00281918