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Cottbus, Germany

Von Minckwitz G.,German Breast Group | Eidtmann H.,Universitats Frauenklinik | Rezai M.,Luisenkrankenhaus | Fasching P.A.,Friedrich - Alexander - University, Erlangen - Nuremberg | And 19 more authors.
New England Journal of Medicine | Year: 2012

BACKGROUND: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor A, has shown clinical efficacy in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. We evaluated the efficacy, measured according to the rate of pathological complete response (absence of invasive and intraductal disease in the breast and the axillary lymph nodes), and the safety of adding bevacizumab to neoadjuvant chemotherapy in patients with early-stage breast cancer. METHODS: We randomly assigned 1948 patients with a median tumor size of 40 mm on palpation to receive neoadjuvant epirubicin and cyclophosphamide followed by docetaxel, with or without concomitant bevacizumab. Patients with untreated HER2-negative breast cancer were eligible if they had large tumors, hormone-receptor-negative disease, or hormone-receptor-positive disease with palpable nodes or positive findings on sentinel-node biopsy, and no increased cardiovascular or bleeding risk. RESULTS: Overall, the rates of pathological complete response were 14.9% with epirubicin and cyclophosphamide followed by docetaxel and 18.4% with epirubicin and cyclophosphamide followed by docetaxel plus bevacizumab (odds ratio with addition of bevacizumab, 1.29; 95% confidence interval, 1.02 to 1.65; P = 0.04); the corresponding rates of pathological complete response were 27.9% and 39.3% among 663 patients with triple-negative tumors (P = 0.003) and 7.8% and 7.7% among 1262 patients with hormone-receptor-positive tumors (P = 1.00). Breast-conserving surgery was possible in 66.6% of the patients in both groups. The addition of bevacizumab, as compared with neoadjuvant therapy alone, was associated with a higher incidence of grade 3 or 4 toxic effects (febrile neutropenia, mucositis, the hand-foot syndrome, infection, and hypertension) but with a similar incidence of surgical complications. CONCLUSIONS: The addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response among patients with HER2-negative early-stage breast cancer. Efficacy was restricted primarily to patients with triple-negative tumors, in whom the pathological complete response is considered to be a reliable predictor of long-term outcome. (Funded by Sanofi-Aventis and Roche, Germany; ClinicalTrials.gov number, NCT00567554.) Copyright © 2012 Massachusetts Medical Society. Source

Stintzing S.,Ludwig Maximilians University of Munich | Fischer von weikersthal L.,Gesundheitszentrum St. Marien | Decker T.,Onkologie Ravensburg | Vehling-kaiser U.,Onkologische Praxis | And 10 more authors.
Annals of Oncology | Year: 2012

Background: The AIO KRK-0306 trial compares the efficacy of infusional 5-fluorouracil, folinic acid, irinotecan (FOLFIRI) plus cetuximab with FOLFIRI plus bevacizumab in first-line treatment of metastatic colorectal cancer (mCRC). In October 2008, an amendment terminated the inclusion of patients with KRAS-mutated tumours. This subgroup of patients is evaluated in the present analysis, while the study is ongoing for patients with KRAS wild-type tumours. Methods: Patients were randomly assigned to FOLFIRI (Tournigand regimen) every 2 weeks plus cetuximab (400 mg/m 2 day 1, followed by 250 mg/m 2 weekly = arm A) or bevacizumab (5 mg/kg every 2 weeks = arm B). Among 336 randomised patients, KRAS mutation was demonstrated in 100 assessable patients. The primary study end point was objective response rate (ORR). Results: ORR was 44% [95% confidence interval (CI) 29% to 59%] in arm A versus 48% (95% CI, 33% to 62%) in arm B. Progression-free survival was 7.5 versus 8.9 months (hazard ratio: 1.0) and overall survival was 22.7 versus 18.7 months (hazard ratio: 0.86) in arms A versus B, respectively. Conclusions: This is the first head to head comparison of cetuximab versus bevacizumab in first-line treatment of mCRC. In the present evaluation of patients with KRAS-mutated tumours, neither strategy demonstrated a clearly superior outcome. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Source

Klement R.J.,Leopoldina Hospital Schweinfurt | Fink M.K.,Onkologische Praxis
Oncogenesis | Year: 2016

As more and more links between cancer and metabolism are discovered, new approaches to treat cancer using these mechanisms are considered. Dietary restriction of either calories or macronutrients has shown great potential in animal studies to both reduce the incidence and growth of cancer, and to act synergistically with other treatment strategies. These studies have also shown that dietary restriction simultaneously targets many of the molecular pathways that are targeted individually by anticancer drugs. The insulin/insulin-like growth factor-1 (IGF-1) system has thereby emerged as a key regulator of cancer growth pathways. Although lowering of insulin levels with diet or drugs such as metformin and diazoxide seems generally beneficial, some practitioners also utilize strategic elevations of insulin levels in combination with chemotherapeutic drugs. This indicates a broad spectrum of possibilities for modulating the insulin/IGF-1 system in cancer treatment. With a specific focus on dietary restriction, insulin administration and the insulin-lowering drug diazoxide, such modifications of the insulin/IGF-1 system are the topic of this review. Although preclinical data are promising, we point out that insulin regulation and the metabolic response to a certain diet often differ between mice and humans. Thus, the need for collecting more human data has to be emphasized. Source

Al-Batran S.-E.,University Cancer Center | Hozaeel W.,University Cancer Center | Tauchert F.K.,Clinic for Oncology and Hematology | Hofheinz R.-D.,University of Mannheim | And 10 more authors.
Annals of Oncology | Year: 2015

Background: Docetaxel is a widely used cytotoxic agent. This study evaluates the impact of docetaxel toxicities on patient's health-related quality of life (QoL). Patients and methods: We conducted a multicenter, prospective, non-interventional trial, in which the QoL was assessed using the EORTC QLQ-C30 questionnaires at baseline and every 4 weeks up to 40 weeks in patients receiving a docetaxel-based chemotherapy for metastatic disease. Treatment-related adverse events were correlated with the corresponding QoL scores. Uni-and multivariate analyses were applied. Results: From January 2008 to June 2011, a total of 2659 patients were included. The majority of patients (48.1%) had prostate cancer, followed by breast (17.1%) and non-small-cell-lung cancer (15.8%). Patients received a median of 5 docetaxel cycles with the median dose of 75 mg/m2. The presence of grade 3/4 diarrhea showed the strongest effect on global health status/QoL average scores (50.91 versus 33.06), followed by vomiting (50.91 versus 35.17), dyspnea (50.94 versus 35.81), mucositis/stomatitis (50.88 versus 36.41), nausea (50.91 versus 36.68), infection (50.90 versus 37.14), fatigue (50.90 versus 43.82) and anemia (50.91 versus 41.03), P < 0.05 for all comparisons. Grade 3/4 leukopenia/neutropenia, alopecia, constipation, neurotoxicity and nail disorders had no significant impact on the global health status/QoL or other items. Conclusion: In this large non-interventional trial, docetaxel-associated grade 3 or 4 toxicities were shown to have a strong detrimental effect on patient's QoL. Notably, diarrhea and vomiting had the strongest negative impact on QoL measures. This has to be kept in mind while making therapeutic decisions and providing optimized supportive treatment measures. Clinical trials number: This study was registered at Deutsches Krebsstudienregister (DKSR, primary registry in the WHO Registry Network) with the ID 527. © The Author 2015. Source

Betticher D.C.,Clinics of Medical Oncology | Delmore G.,Medizinische Onkologie | Breitenstein U.,OnkoZentrum Zurich | Anchisi S.,Hopital de Sion | And 8 more authors.
Supportive Care in Cancer | Year: 2013

Purpose: Chemotherapy-induced alopecia is very distressing for a patient and may have an impact on treatment decisions. On docetaxel-based therapy, alopecia occurs in a substantial proportion of patients. We aimed to investigate whether two different methods of scalp cooling can prevent hair loss. Methods: In this open-label, prospective, nonrandomized trial, patients with solid tumors receiving docetaxel in a palliative setting were allocated according to patients' preference to short-term cooling (over 45 min postinfusion) with a Paxman® PSC-2 machine (PAX), with cold cap (CC), or no cooling. The combined endpoint was alopecia World Health Organisation (WHO) III or IV or the necessity to wear a wig. Study identifier is Clinicaltrials.gov NCT01008774. Results: Two hundred thirty-eight patients were included in the trial (128 patients PAX, 71 CC, and 39 no cooling). Number of cycles (median 4) and median docetaxel doses were similar across groups (55-60 mg/day on weekly therapy, 135-140 mg/day on 3-weekly therapy). Alopecia occurred with PAX, CC, and no cooling under 3-weekly docetaxel in 23, 27, and 74 % and under weekly docetaxel in 7, 8, and 17 %, respectively. Overall, cooling (PAX and CC combined) reduced risk of alopecia by 78 % (hazard ratio 0.22; 95 % confidence interval 0.12 to 0.41). CC and PAX prophylaxis led to the same degree of prevention of alopecia. Adverse events (AE) were reported in 5 % (most frequently, sensation of cold), and 30 patients (13 %) discontinued cooling measures after cycle 1. Conclusions: In this first comparison published to date, both PAX and CC offer efficacious protection against hair loss, in particular when docetaxel is administered in a 3-weekly interval. © 2013 Springer-Verlag Berlin Heidelberg. Source

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