scispace - formally typeset
Search or ask a question
Author

Nils Homann

Bio: Nils Homann is an academic researcher from Helsinki University Central Hospital. The author has contributed to research in topics: Docetaxel & Oxaliplatin. The author has an hindex of 20, co-authored 66 publications receiving 3808 citations.


Papers
More filters
Journal ArticleDOI
TL;DR: In this article, the safety and efficacy of the docetaxel-based triplet FLOT (fluorouracil plus leucovorin, oxaliplatin, and doceteaxel) as a perioperative therapy for patients with locally advanced, resectable tumours was reported.

1,218 citations

Journal ArticleDOI
TL;DR: In older adult patients, FLO also seemed to be associated with improved efficacy in patients with advanced gastric cancer, and in patients older than 65 years, this study found that FLO reduced toxicity as compared with FLP.
Abstract: Purpose This study was designed to compare fluorouracil, leucovorin, and oxaliplatin with fluorouracil, leucovorin, and cisplatin in patients with advanced gastric cancer. Patients and Methods Patients with previously untreated advanced adenocarcinoma of the stomach or esophagogastric junction were randomly assigned to receive either fluorouracil 2,600 mg/m2 via 24-hour infusion, leucovorin 200 mg/m2, and oxaliplatin 85 mg/m2 (FLO) every 2 weeks or fluorouracil 2,000 mg/m2 via 24-hour infusion, leucovorin 200 mg/m2 weekly, and cisplatin 50 mg/m2 every 2 weeks (FLP). The primary end point was progression-free survival (PFS). Results Two hundred twenty patients (median age, 64 years; metastatic, 94%) were randomly assigned. FLO was associated with significantly less (any grade) anemia (54% v 72%), nausea (53% v 70%), vomiting (31% v 52%), alopecia (22% v 39%), fatigue (19% v 34%), renal toxicity (11% v 34%), thromboembolic events (0.9% v 7.8%), and serious adverse events related to the treatment (9% v 19%)....

659 citations

Journal ArticleDOI
TL;DR: Findings from the phase 2 part of the FLOT4 trial, which compared histopathological regression in patients treated with a docetaxel-based triplet chemotherapy versus an anthracycline-based doublet chemotherapy before surgical resection, suggest FLOT was associated with significantly higher proportions of patients achieving pathological complete regression than was ECF/ECX.
Abstract: Summary Background Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma, but has not yet been evaluated in the context of resectable patients. Here we report findings from the phase 2 part of the phase 2/3 FLOT4 trial, which compared histopathological regression in patients treated with a docetaxel-based triplet chemotherapy versus an anthracycline-based triplet chemotherapy before surgical resection. Methods In this randomised, open-label, phase 2/3 study, eligible participants were recruited from 28 German oncology centres. Patients with resectable gastric or gastro-oesophageal junction cancer who had clinical stage cT2 or higher, nodal positive (cN+) disease, or both were randomly assigned (1:1) to either three preoperative and three postoperative 3-week cycles of intravenous epirubicin 50 mg/m 2 on day 1, intravenous cisplatin 60 mg/m 2 on day 1, and either fluorouracil 200 mg/m 2 as continuous intravenous infusion or capecitabine 1250 mg/m 2 orally (two doses of 625 mg/m 2 per day) on days 1 to 21 (ECF/ECX group) or four preoperative and four postoperative 2-week cycles of docetaxel 50 mg/m 2 , intravenous oxaliplatin 85 mg/m 2 , intravenous leucovorin 200 mg/m 2 , and fluorouracil 2600 mg/m 2 as a 24 h infusion, all on day 1 (FLOT group). Randomisation was done centrally with an interactive web-response system based on a sequence generated with blocks (block size 2) stratified by Eastern Cooperative Oncology Group performance status, location of primary tumour, age, and nodal status. No masking was done. Central assessment of pathological regression was done according to the Becker criteria. The primary endpoint was pathological complete regression (tumour regression grade TRG1a) and was analysed in the modified intention-to-treat population, defined as all patients who were randomly assigned to treatment excluding patients who had surgery but did not provide resection specimens for central evaluation. The study (including the phase 3 part) has completed enrolment, but follow-up is ongoing and this is an interim analysis. The trial is registered with ClinicalTrials.gov, number NCT01216644. Findings Between Aug 18, 2010, and Aug 10, 2012, 300 patients (152 patients in the ECF/ECX group; 148 patients in the FLOT group) were enrolled into the phase 2 part of the study, 265 of whom (137 in the ECF/ECX group; 128 in the FLOT group) were assessable on a modified intention-to-treat basis. 119 (93%) of 128 patients in the FLOT group and 126 (92%) of 137 patients in the ECF/ECX group were given all planned preoperative cycles of treatment. FLOT was associated with significantly higher proportions of patients achieving pathological complete regression than was ECF/ECX (20 [16%; 95% CI 10–23] of 128 patients vs eight [6%; 3–11] of 137 patients; p=0·02). 44 (40%) of 111 patients in the ECF/ECX group and 30 (25%) of 119 patients in the FLOT group had at least one serious adverse event involving a perioperative medical or surgical complication. The most common non-surgical grade 3–4 adverse events were neutropenia (52 [38%] of 137 patients in the ECF/ECX group vs 67 [52%] of 128 patients in the FLOT group), leucopenia (28 [20%] vs 36 [28%]), nausea (23 [17%] vs 12 [9%]), infection (16 [12%] vs 15 [12%]), fatigue (19 [14%] vs 11 [9%]), and vomiting (13 [10%] vs four [3%]). Interpretation Perioperative FLOT was active and feasible to administer, and might represent an option for patients with locally advanced, resectable gastric or gastro-eosophageal junction adenocarcinoma. Funding None.

476 citations

Journal ArticleDOI
TL;DR: Increased local microbial salivary acetaldehyde production due to ethanol among smokers and heavy drinkers could be a biological explanation for the observed synergistic carcinogenic action of alcohol and smoking on upper gastrointestinal tract cancer.
Abstract: The pathogenetic mechanisms behind alcohol-associated carcinogenesis in the upper digestive tract remain unclear, as alcohol is not carcinogenic. However, there is increasing evidence that a major part of the tumour-promoting action of alcohol might be mediated via its first, toxic and carcinogenic metabolite acetaldehyde. Acetaldehyde is produced from ethanol in the epithelia by mucosal alcohol dehydrogenases, but much higher levels derive from microbial oxidation of ethanol by the oral microflora. In this study we investigated factors that might alter the composition and quantities of the oral microflora and, consequently, influence microbial acetaldehyde production. Information about dental health, smoking habits, alcohol consumption and other factors was obtained by a questionnaire from 326 volunteers with varying social backgrounds and health status, e.g. oral cavity malignancy. Paraffin-induced saliva was collected and the microbial production of acetaldehyde from ethanol was measured. Smoking and heavy drinking were the strongest factors increasing microbial acetaldehyde production. Whether poor dental status may alter local acetaldehyde production from ethanol remained unanswered. Bacterial analysis revealed that mainly gram-positive aerobic bacteria and yeasts were associated with higher acetaldehyde production. Increased local microbial salivary acetaldehyde production due to ethanol among smokers and heavy drinkers could be a biological explanation for the observed synergistic carcinogenic action of alcohol and smoking on upper gastrointestinal tract cancer. It offers a new microbiological approach to ethanol-associated carcinogenesis at these anatomic sites.

297 citations

Journal ArticleDOI
TL;DR: It is concluded, that the microbial formation of acetaldehyde in saliva could be one explanation for the tumor promoting effect of ethanol on the upper gastrointestinal tract and this may support the epidemiological finding, that poor oral hygiene is an independent risk factor for oral cavity cancer.
Abstract: Chronic ethanol ingestion leads to an enhanced risk of upper gastrointestinal tract cancer. Although many hypotheses for the tumor promoting effect of alcohol exist, the pathogenetic mechanisms remain unclear since alcohol in itself is not carcinogenic. Acetaldehyde, the first metabolite of ethanol, has been shown to have multiple mutagenic effects and to be carcinogenic to animals. Previous research has revealed that acetaldehyde can be formed from ethanol via microbial alcohol dehydrogenase. Thus, at least part of the proposed tumorigenic effect of ethanol may be linked to local production of acetaldehyde from ethanol by oral microflora. In this study we demonstrate the production of marked amounts of acetaldehyde in saliva after ingestion of moderate amounts of ethanol. Considerable inter individual variation in acetaldehyde production capacity is also shown. In vivo acetaldehyde production is significantly reduced after a 3-day use of an antiseptic mouthwash (chlorhexidine). In vitro acetaldehyde production was shown to be linear in time, inhibited by 4-methylpyrazole and it could not be saturated under ethanol conditions that are relevant in vivo. There was a significant positive correlation between salivary acetaldehyde production in vitro and in vivo. We conclude, that the microbial formation of acetaldehyde in saliva could be one explanation for the tumor promoting effect of ethanol on the upper gastrointestinal tract. Moreover, this may support the epidemiological finding, that poor oral hygiene is an independent risk factor for oral cavity cancer.

290 citations


Cited by
More filters
01 Jan 2014
TL;DR: Lymphedema is a common complication after treatment for breast cancer and factors associated with increased risk of lymphedEMA include extent of axillary surgery, axillary radiation, infection, and patient obesity.

1,988 citations

Journal ArticleDOI
TL;DR: Capecitabine and oxaliplatin are as effective as fluorouracil and cisplatin, respectively, in patients with previously untreated esophagogastric cancer, in a two-by-two design.
Abstract: For the capecitabine–fluorouracil comparison, the hazard ratio for death in the capecitabine group was 0.86 (95% confidence interval [CI], 0.80 to 0.99); for the oxaliplatin–cisplatin comparison, the hazard ratio for the oxaliplatin group was 0.92 (95% CI, 0.80 to 1.10). The upper limit of the confidence intervals for both hazard ratios excluded the predefined noninferiority margin of 1.23. Median survival times in the ECF, ECX, EOF, and EOX groups were 9.9 months, 9.9 months, 9.3 months, and 11.2 months, respectively; survival rates at 1 year were 37.7%, 40.8%, 40.4%, and 46.8%, respectively. In the secondary analysis, overall survival was longer with EOX than with ECF, with a hazard ratio for death of 0.80 in the EOX group (95% CI, 0.66 to 0.97; P = 0.02). Progression-free survival and response rates did not differ significantly among the regimens. Toxic effects of capecitabine and fluorouracil were similar. As compared with cisplatin, oxaliplatin was associated with lower incidences of grade 3 or 4 neutropenia, alopecia, renal toxicity, and thromboembolism but with slightly higher incidences of grade 3 or 4 diarrhea and neuropathy. Conclusions Capecitabine and oxaliplatin are as effective as fluorouracil and cisplatin, respectively, in patients with previously untreated esophagogastric cancer. (Current Controlled Trials number, ISRCTN51678883.)

1,987 citations

Journal ArticleDOI
TL;DR: This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.
Abstract: Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

1,545 citations

Journal ArticleDOI
TL;DR: In this article, the safety and efficacy of the docetaxel-based triplet FLOT (fluorouracil plus leucovorin, oxaliplatin, and doceteaxel) as a perioperative therapy for patients with locally advanced, resectable tumours was reported.

1,218 citations