Von Weikersthal L.F.,Klinikum Sankt Marien |
Schalhorn A.,Ludwig Maximilians University of Munich |
Stauch M.,Oncological Practice |
Quietzsch D.,Klinikum Chemnitz |
And 16 more authors.
European Journal of Cancer | Year: 2011
Purpose: To determine whether irinotecan plus oxaliplatin (mIROX) is superior to irinotecan plus infusional 5-fluorouracil, leucovorin (FUFIRI) as first-line therapy of patients with metastatic colorectal cancer (mCRC). Patients and methods: A phase III, randomised, open-label multicentre study compared standard treatment with FUFIRI (irinotecan 80 mg/m2, 5-fluorouracil 2000 mg/m2, folinic acid 500 mg/m2 weekly times 6) to mIROX using an identical schedule of irinotecan plus oxaliplatin 85 mg/m2 applied on days 1, 15 and 29 of a 7-week cycle. The primary end-point was progression-free survival (PFS). Results: A total of 479 eligible patients were randomly assigned. Progression-free survival was 7.2 months in the mIROX arm and 8.2 months in the FUFIRI arm [hazard ratio = 1.14; 95% confidence interval (CI) 0.94-1.37; P = 0.178]. Comparable results were also obtained for overall survival time with 19 months in the mIROX-arm and 22 months in the FUFIRI-arm (hazard ratio = 1.08, P = 0.276). Both regimens induced an identical objective response rate (ORR) of 41%, but disease control rate (ORR plus stable disease) was significantly greater in the FUFIRI group (81% versus 68%, P = 0.001). Most frequent grades 1-4 side-effects of mIROX and FUFIRI treatment were nausea (80% versus 73%) and delayed diarrhoea (79% versus 68%). Grades 3-4 toxicities were generally below 10%, except for diarrhoea which was more frequent in the mIROX-arm compared to the FUFIRI-arm (19% versus 30%, P = 0.006) Conclusion: mIROX failed to show superior activity compared to high-dose 5-FU/folinic acid plus irinotecan. Due to better tolerability the combination of high-dose 5-FU/folinic acid and irinotecan remains a standard of care in first-line treatment of metastatic colorectal cancer. © 2010 Elsevier Ltd. All rights reserved.
A randomized, phase III trial of capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in first-line treatment of metastatic colorectal cancer: The AIO KRK 0110 Trial/ML22011 Trial
Giessen C.,Ludwig Maximilians University of Munich |
von Weikersthal L.F.,MVZ Gesundheitszentrum St. Marien |
Hinke A.,WISP GmbH |
Stintzing S.,Ludwig Maximilians University of Munich |
And 12 more authors.
BMC Cancer | Year: 2011
Background: Several randomized trials have indicated that combination chemotherapy applied in metastatic colorectal cancer (mCRC) does not significantly improve overall survival when compared to the sequential use of cytotoxic agents (CAIRO, MRC Focus, FFCD 2000-05). The present study investigates the question whether this statement holds true also for bevacizumab-based first-line treatment including escalation- and de-escalation strategies.Methods/Design: The AIO KRK 0110/ML22011 trial is a two-arm, multicenter, open-label randomized phase III trial comparing the efficacy and safety of capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in the first-line treatment of metastatic colorectal cancer. Patients with unresectable metastatic colorectal cancer, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, will be assigned in a 1:1 ratio to receive either capecitabine 1250 mg/m2bid for 14d (d1-14) plus bevacizumab 7.5 mg/kg (d1) q3w (Arm A) or capecitabine 800 mg/m2BID for 14d (d1-14), irinotecan 200 mg/m2(d1) and bevacizumab 7.5 mg/kg (d1) q3w (Arm B). Patients included into this trial are required to consent to the analysis of tumour tissue and blood for translational investigations. In Arm A, treatment escalation from Cape-Bev to CAPIRI-Bev is recommended in case of progressive disease (PD). In Arm B, de-escalation from CAPIRI-Bev to Cape-Bev is possible after 6 months of treatment or in case of irinotecan-associated toxicity. Re-escalation to CAPIRI-Bev after PD is possible. The primary endpoint is time to failure of strategy (TFS). Secondary endpoints are overall response rate (ORR), overall survival, progression-free survival, safety and quality of life.Conclusion: The AIO KRK 0110 trial is designed for patients with disseminated, but asymptomatic mCRC who are not potential candidates for surgical resection of metastasis. Two bevacizumab-based strategies are compared: one starting as single-agent chemotherapy (Cape-Bev) allowing escalation to CAPIRI-Bev and another starting with combination chemotherapy (CAPIRI-Bev) and allowing de-escalation to Cape-Bev and subsequent re-escalation if necessary.Trial Registration: ClinicalTrials.gov Identifier NCT01249638. EudraCT-No.: 2009-013099-38. © 2011 Giessen et al.; licensee BioMed Central Ltd.
Heinemann V.,Ludwig Maximilians University of Munich |
von Weikersthal L.F.,Gesundheitszentrum St Marien |
Decker T.,Oncological Practice |
Kiani A.,Klinikum Bayreuth GmbH |
And 22 more authors.
The Lancet Oncology | Year: 2014
Background: Cetuximab and bevacizumab have both been shown to improve outcomes in patients with metastatic colorectal cancer when added to chemotherapy regimens; however, their comparative effectiveness when partnered with first-line fluorouracil, folinic acid, and irinotecan (FOLFIRI) is unknown. We aimed to compare these agents in patients with KRAS (exon 2) codon 12/13 wild-type metastatic colorectal cancer. Methods: In this open-label, randomised, phase 3 trial, we recruited patients aged 18-75 years with stage IV, histologically confirmed colorectal cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, an estimated life expectancy of greater than 3 months, and adequate organ function, from centres in Germany and Austria. Patients were centrally randomised by fax (1:1) to FOLFIRI plus cetuximab or FOLFIRI plus bevacizumab (using permuted blocks of randomly varying size), stratified according to ECOG performance status, number of metastatic sites, white blood cell count, and alkaline phosphatase concentration. The primary endpoint was objective response analysed by intention to treat. The study has completed recruitment, but follow-up of participants is ongoing. The trial is registered with ClinicalTrials.gov, number NCT00433927. Findings: Between Jan 23, 2007, and Sept 19, 2012, 592 patients with KRAS exon 2 wild-type tumours were randomly assigned and received treatment (297 in the FOLFIRI plus cetuximab group and 295 in the FOLFIRI plus bevacizumab group). 184 (62·0%, 95% CI 56·2-67·5) patients in the cetuximab group achieved an objective response compared with 171 (58·0%, 52·1-63·7) in the bevacizumab group (odds ratio 1·18, 95% CI 0·85-1·64; p=0·18). Median progression-free survival was 10·0 months (95% CI 8·8-10·8) in the cetuximab group and 10·3 months (9·8-11·3) in the bevacizumab group (hazard ratio [HR] 1·06, 95% CI 0·88-1·26; p=0·55); however, median overall survival was 28·7 months (95% CI 24·0-36·6) in the cetuximab group compared with 25·0 months (22·7-27·6) in the bevacizumab group (HR 0·77, 95% CI 0·62-0·96; p=0·017). Safety profiles were consistent with the known side-effects of the study drugs. The most common grade 3 or worse adverse events in both treatment groups were haematotoxicity (73 [25%] of 297 patients in the cetuximab group vs 62 [21%] of 295 patients in the bevacizumab group), skin reactions (77 [26%] vs six [2%]), and diarrhoea (34 [11%] vs 40 [14%]). Interpretation: Although the proportion of patients who achieved an objective response did not significantly differ between the FOLFIRI plus cetuximab and FOLFIRI plus bevacizumab groups, the association with longer overall survival suggests that FOLFIRI plus cetuximab could be the preferred first-line regimen for patients with KRAS exon 2 wild-type metastatic colorectal cancer. Funding: Merck KGaA. © 2014 Elsevier Ltd.
PubMed | Gesundheitszentrum St. Marien, Haematology and Oncology, Ludwig Maximilians University of Munich, Johannes Gutenberg University Mainz and 5 more.
Type: | Journal: International journal of cancer | Year: 2016
We explored the association of early tumor shrinkage (ETS) and non-ETS with efficacy of first-line and consecutive second-line treatment in patients with KRAS wild-type metastatic colorectal cancer treated in FIRE-3. Assessment of tumor shrinkage was based on the sum of longest diameters of target lesions, evaluated after six weeks of treatment. Shrinkage was classified as ETS (shrinkage by20%), mETS (shrinkage by 0% - <20%), mPD (minor progression >0% - <20%) and PD (progression 20%). Overall survival (OS) was 33.2 (95% CI 28.0-38.4) months in ETS patients, while non-ETS was associated with less favourable outcome (mETS 24.0 (95% CI 21.2-26.9) months, mPD 19.0 (95% CI 13.0-25.0) months, PD 12.8 (95% CI 11.1-14.5) months). Differences in PFS of first-line therapy were less pronounced. ETS subgroups defined in 1st-line therapy also correlated with efficacy of 2nd-line therapy. Progression-free survival in 2nd-line (PFS2nd) was 6.5 months (5.8-7.2) for ETS, and was 5.6 (95% CI 4.7-6.5) months for mETS, 4.9 (95% CI 3.7-6.1) months for mPD and 3.3 (95% CI 2.3-4.3) months for PD. PFS of first-line and PFS2nd showed a linear correlation (Bravais-Pearson coefficient: 0.16, P=0.006). While ETS is associated with the most favourable outcome, non-ETS represents a heterogeneous subgroup with distinct characteristics of less favourable initial tumor response to treatment. This is the first analysis to demonstrate that early tumor response observed during 1st-line FOLFIRI-based therapy may also relate to efficacy of 2
Viel E.,Oncological Practice |
Vanoli A.,Oncological Practice |
Melis A.,Oncological Practice |
Rocher F.,Oncology and Radiotherapy Center Du Parc |
And 2 more authors.
Climacteric | Year: 2016
ABSTRACT: Objectives: This paper aims to highlight the efficiency of auriculotherapy in the treatment of hot flushes, especially in cancer-related menopausal transition. Methods: We used systematically collected data from patients in 2014 in a medical oncology practice. The treatment was made according to the guidelines of The Inter-University Diploma and the cartography of the World Health Organization; data on satisfaction were collected orally. Results: In 2014, 49 patients, among whom 41 had cancer, were treated for hot flushes. Although it is not recommended to treat several symptoms during the same session, we dealt with 1.7 symptoms per session on average. Sixty-nine percent of the patients were satisfied. We lacked data for nine patients, who did not come to the minimal recommended number of treatments (three). Only one patient among those who did not observe any improvement received three treatments. Conclusions: Auricular acupuncture is a safe and cheap method to treat hot flushes. It has been effective in numerous and various cases, among which were patients who presented cancer-related menopausal symptoms. It may be applied for a large variety of other symptoms. © 2016 International Menopause Society.
Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin or cisplatin in patients with advanced non-small-cell lung cancer (NSCLC)
PubMed | Pulmonology and Oncology, University of Tübingen, University of Bonn, University of Duisburg - Essen and 10 more.
Type: Journal Article | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2016
Variable chemotherapy exposure may cause toxicity or lack of efficacy. This study was initiated to validate pharmacokinetically (PK)-guided paclitaxel dosing in patients with advanced non-small-cell lung cancer (NSCLC) to avoid supra- or subtherapeutic exposure.Patients with newly diagnosed, advanced NSCLC were randomly assigned to receive up to 6 cycles of 3-weekly carboplatin AUC 6 or cisplatin 80 mg/m(2) either with standard paclitaxel at 200 mg/m(2) (arm A) or PK-guided dosing of paclitaxel (arm B). In arm B, initial paclitaxel dose was adjusted to body surface area, age, sex, and subsequent doses were guided by neutropenia and previous-cycle paclitaxel exposure [time above a plasma concentration of 0.05 M (Tc>0.05)] determined from a single blood sample on day 2. The primary end point was grade 4 neutropenia; secondary end points included neuropathy, radiological response, progression-free survival (PFS) and overall survival (OS).Among 365 patients randomly assigned, grade 4 neutropenia was similar in both arms (19% versus 16%; P = 0.10). Neuropathy grade 2 (38% versus 23%, P < 0.001) and grade 3 (9% versus 2%, P < 0.001) was significantly lower in arm B, independent of the platinum drug used. The median final paclitaxel dose was significantly lower in arm B (199 versus 150 mg/m(2), P < 0.001). Response rate was similar in arms A and B (31% versus 27%, P = 0.405), as was adjusted median PFS [5.5 versus 4.9 months, hazard ratio (HR) 1.16, 95% confidence interval (CI) 0.91-1.49, P = 0.228] and OS (10.1 versus 9.5 months, HR 1.05, 95% CI 0.81-1.37, P = 0.682).PK-guided dosing of paclitaxel does not improve severe neutropenia, but reduces paclitaxel-associated neuropathy and thereby improves the benefit-risk profile in patients with advanced NSCLC.NCT01326767 (https://clinicaltrials.gov/ct2/show/NCT01326767).
Stemmler H.J.,Ludwig Maximilians University of Munich |
Digioia D.,Ludwig Maximilians University of Munich |
Freier W.,Oncological Practice |
Tessen H.W.,Oncological Practice |
And 10 more authors.
British Journal of Cancer | Year: 2011
Background:An increasing proportion of patients are exposed to anthracyclines and/or taxanes in the adjuvant or neoadjuvant setting. Re-exposure in the metastatic stage is limited by drug resistance, thus evaluation of non-cross-resistant regimens is mandatory.Methods:Anthracycline- pretreated patients were randomly assigned to three gemcitabine-based regimens. Chemotherapy consisted of gemcitabine 1.000 mg m-2 plus vinorelbin 25 mg m-2 on days 18 (GemVin), or plus cisplatin 30 mg m 2 on days 18 (GemCis), or plus capecitabine 650 mg m-2 b.i.d. orally days 1-14 (GemCap), q3w. The primary end point was response rate.Results:A total of 141 patients were recruited on the trial. The overall response rates were 39.0% (GemVin), 47.7% (GemCis) and 34.7% (GemCap). Median progression-free survival was estimated with 5.7, 6.9 and 8.3 months, respectively. Corresponding median survival times were 17.5 (GemVin), 13.0 (GemCis) and 19.4 months (GemCap). Neutropenia grade 3 occurred in 16.7% (Gem/Vin), 4.4% (GemCis) and 0% (Gem/Cap), whereas non-haematological toxicities were rarely severe except grade 3 hand-foot syndrome in 2.0% of the GemCap patients (per patient analysis).Conclusions:This randomised phase II trial has revealed comparable results for three gemcitabine-based regimens regarding treatment efficacy and toxicity. Gemcitabine-based chemotherapy appears to be a worthwhile treatment option for pretreated patients with metastatic breast cancer. © 2011 Cancer Research UK All rights reserved.
Uster A.,Kantonsspital Winterthur |
Ruefenacht U.,Kantonsspital Winterthur |
Ruehlin M.,Kantonsspital Winterthur |
Pless M.,Kantonsspital Winterthur |
And 4 more authors.
Nutrition | Year: 2013
Objective: Weight loss is common in patients with malignant tumors and it can adversely affect quality of life and survival. The aim of the present study was to investigate the effects of a nutritional intervention in cancer patients in an outpatient setting. Methods: Cancer outpatients (N = 58) who were classified as undernourished or at high risk for undernutrition by the Nutritional Risk Screening 2002 tool were randomized into two groups. One group (n = 30) received standardized individual nutritional therapy, including counseling by a dietitian, food fortification, and oral nutritional supplements if required. The second group (n = 28) received standard care. The nutritional intervention lasted 3 mo. Dietary intake (3-d dietary record), nutritional status (body weight), physical functioning (performance status, hand-grip strength) and quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire version 3.0) were assessed at baseline and after 6 wk and 3 mo. An additional follow-up assessment was carried out 3 mo post-intervention. Results: Nutritional intervention led to a significantly higher average energy and protein intake in the nutritional therapy group (+379 kcal; 95% confidence interval [CI], 117-642; P = 0.007, respectively; +10.4 g; 95% CI, 2.3-18.5; P = 0.016). However, the increased dietary intake was not associated with improvements in nutritional status, physical functioning, or quality of life. Conclusions: Individual nutritional counseling significantly and positively influenced energy and protein intake, but did not improve nutritional or physical outcome or quality of life. These results indicate that nutritional therapy alone is of limited efficacy in cancer patients whose nutritional status has already deteriorated. © 2013 Elsevier Inc.
Huober J.,Breast Center Kantonsspital |
Fett W.,Oncological Practice |
Nusch A.,Oncological Practice |
Neise M.,Oncological Practice |
And 6 more authors.
BMC Cancer | Year: 2010
Background: Pegylated liposomal doxorubicin (PLD) is active in metastatic breast cancer. This observational study evaluated the efficacy and safety of PLD in patients treated during routine clinical practice.Methods: Eligible patients had metastatic breast cancer and were treated with PLD according to the dose and schedule determined by their physician as part of routine practice. The primary objectives were to analyze the efficacy and toxicity of PLD therapy.Results: 125 patients were assessable. Median age was 62 years, 78% had performance status 0-1, and 60% had estrogen-receptor-positive disease. PLD treatment was second- or third-line in 69% of patients. Prior anthracyclines (adjuvant or metastatic) had been used in 56% of patients. The majority of patients (79%) received PLD every 4 weeks at a median dose of 40 mg/m 2. Overall response rate was 43% in all patients and 34% in those previously treated with anthracyclines. The most common grade 3/4 adverse events were skin toxicity/hand-foot syndrome (6%), and leukopenia (3%).Conclusions: This observational study supports the activity and tolerability of PLD in metastatic breast cancer as demonstrated in PLD clinical trials. © 2010 Huober et al; licensee BioMed Central Ltd.
Heinemann V.,Ludwig Maximilians University of Munich |
di Gioia D.,Ludwig Maximilians University of Munich |
Vehling-Kaiser U.,Oncological Practice |
Harich H.-D.,Oncological Practice |
And 9 more authors.
Annals of Oncology | Year: 2011
Background: To evaluate the efficacy and safety of oral and i.v. vinorelbine plus trastuzumab as first-line regimen in a patient-convenient application for human epidermal growth factor receptor 2 (HER2)-overexpressing patients with metastatic breast cancer. Patients and methods: Forty-two women were enrolled in a multicenter study. The patients received i.v. vinorelbine at a dose of 25 mg/m2 on day 1 followed by oral vinorelbine at a dose of 60 mg/m2 on days 8 and 15 in a 3-week cycle. Standard dose trastuzumab was given at 3-week intervals. Results: Complete response was observed in 7 patients (18.9%) and partial response in 19 patients (51.4%), for an overall response rate of 70.3% [95% confidence interval (CI) 53.0-84.1]. The disease control rate reached 91.9% (95% CI 78.1-98.3). The median time to progression was 9.3 months, while median overall survival reached 35.6 months. Hematological and non-hematological toxic effects were acceptable with grade 3-4 leukopenia of 14% and neutropenia of 38%; cardiac toxicity did not reach the level of clinical relevance. Conclusion: The combination of i.v. and oral vinorelbine plus trastuzumab demonstrates high activity and good tolerability in first-line treatment of HER2-overexpressing metastatic breast cancer. In addition, it offers convenience for the patients with only one i.v. treatment every 3 weeks. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.