Cetuximab plus chronomodulated irinotecan, 5-fluorouracil, leucovorin and oxaliplatin as neoadjuvant chemotherapy in colorectal liver metastases: POCHER trial

Background:We assessed the effectiveness of cetuximab plus chronomodulated irinotecan, 5-fluorouracil (5-FU), leucovorin (FA) and oxaliplatin (L-OHP) (chrono-IFLO) administered as neoadjuvant chemotherapy to increase the resectability of colorectal liver metastases.Methods:This was a phase II prospective trial with rate of liver metastases resection as primary end point. Forty-three patients with unresectable metastases were enroled: 9 with metastases >5 cm; 29 with multinodular (4) disease; 1 with hilar location; 4 with extrahepatic lung disease. Treatment consisted of cetuximab at day 1 plus chronomodulated irinotecan 5-FU, FA and L-OHP for 2-6 days every 2 weeks. After the first 17 patients, doses were reduced for irinotecan to 110 mg m 2, 5-FU to 550 mg m 2 per day and L-OHP to 15 mg m 2 per day.Results:Macroscopically complete resections were performed in 26 out of 43 patients (60%) after a median of 6 (range 3-15) cycles. Partial response was noticed in 34 patients (79%). Median overall survival was 37 months (95% CI: 21-53 months), with a 2-year survival of 68% in the entire population, 80.6% in resected patients and 47.1% in unresected patients (P=0.01). Grade 3/4 diarrhoea occurred in 93% and 36% of patients before and after dose reduction.Conclusion:Cetuximab plus chrono-IFLO achieved 60% complete resectability of colorectal liver metastases. © 2010 Cancer Research UK All rights reserved

Polymorphism at High Molecular Weight Glutenin Subunits and Morphological Diversity of Aegilops geniculata Roth Collected in Algeria

A collection of 35 accessions of the tetraploid wild wheat Aegilops geniculata Roth (MM, UU) sampled in northern Algeria was evaluated for morphological and biochemical variability. Morphological and ecological analyses based on morphological traits and bioclimatic parameters, respectively, were assessed using principal component analysis (PCA). Accessions were differentiated by width characters, namely spike’s width, and a weak relationship between morphological traits and ecological parameters was found. Polymorphism of high molecular weight (HMW) glutenin subunits was carried on by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Among accessions analyzed, 27 alleles were identified at the two loci Glu-M1 and Glu-U1: resulting in twenty-nine patterns and a nomenclature was proposed. Two alleles at the Glu-U1 locus expressed a new subunit with a slightly slower mobility than subunit 8. These results provide new information regarding the genetic variability of HMW glutenin subunits, as well as their usefulness in cultivated wheat quality improvement

Teacher quality in the twenty first century: new lives, old truths

This chapter is based upon a keynote address to the first global teacher education summit, organised by Beijing Normal University in 2011, in which research across the world about influences which affect teachers' sense of professional identity, capacity for compassion, commitment, resilience and effectiveness long after they have graduated from their pre-service education and training programmes in universities and colleges were shared. The findings suggest that teaching pre-service students about how the conditions in which they work may enhance or diminish their capacity to teach to their best and how they might act to mediate these is a key part of the work of all teacher educators and an important focus for the work of educational researchers

Chordoma: clinical characteristics, management and prognosis of a case series of 25 patients

<p>Abstract</p> <p>Background</p> <p>Adequate surgery still remains the only curative treatment of chordoma. Interesting clinical data on advanced disease with molecularly targeted therapies were reported.</p> <p>Methods</p> <p>We described the clinical outcome of a series of chordoma patients followed at Regina Elena National Cancer Centre of Rome from 2004 to 2008.</p> <p>Results</p> <p>Twenty-five consecutive patients with sacral (11 patients), spine (13 patients), and skull base (1 patient) chordoma went to our observation. Six patients (24%) had primary disease, 14(56%) a recurrent disease, and 5(20%) a metastatic spreading. Surgery was the primary option for treatment in 22 out of 25 patients. Surgical margins were wide in 5 (23%) and intralesional in 17(77%) patients; 3 out of 4 in-house treated patients obtained wide margins. After first surgery, radiotherapy (protons or high-energy photons) were delivered to 3 patients. One out of the 5 patients with wide margins is still without evidence of disease at 20 months from surgery; 2 patients died without evidence of disease after 3 and 36 months from surgery. Sixteen out of 17 (94%) patients with intralesional margins underwent local progression at a median time of 18 months with a 2-year local progression-free survival of 47%. The 5-year metastasis-free survival rate was 78.3%. Seventeen patients with locally advanced and/or metastatic disease expressing platelet-derived growth factor receptor (PDGFR) β were treated with imatinib mesylate. A RECIST stabilization of the disease was the best response observed in all treated cases. Pain relief with reduction in analgesics use was obtained in 6 out of 11 (54%) symptomatic patients. The 5- and 10-year survival rates of the entire series of patients were 76.7 and 59.7%, respectively.</p> <p>Conclusions</p> <p>Despite progress of surgical techniques and the results obtained with targeted therapy, more effort is needed for better disease control. Specific experience of the multidisciplinar therapeutic team is, however, essential to succeed in improving patients' outcome.</p

Oxaliplatin and protracted venous infusion of 5-fluorouracil in patients with advanced or relapsed 5-fluorouracil pretreated colorectal cancer

The purpose of this study was to evaluate the activity and safety of oxaliplatin and protracted venous infusion of 5-fluorouracil (PVI 5-FU) in patients with advanced or relapsed 5-FU pretreated colorectal cancer. 38 patients with advanced or metastatic colorectal carcinoma with documented progression on or within 6 months following 5-FU or thymidylate synthase inhibitor containing chemotherapy were recruited between June 1997 and September 2000. Oxaliplatin (100 mg m−2) was given every 2 weeks and PVI 5-FU (300 mg m−2day−1) was administered. Median age of patients was 61 years. 17 patients had >2 sites of disease involvement. 10 had received 5-FU based adjuvant chemotherapy. 16 received oxaliplatin and PVI 5-FU as second-line chemotherapy for advanced disease and 22 as third or subsequent lines. Median follow up was 6.1 months. The best achieved objective tumour response rate was 29% (11 partial responses 95% confidence interval [CI] = 15–46%). 20 patients (52.6%) had stable disease. The median duration of response was 3.9 months. Even for patients who had previously received both 5-FU and irinotecan (n= 22), 27.3% had partial response with oxaliplatin and PVI 5-FU. 37 patients had symptoms on entry into the study. 25 patients had pain, 10 had anorexia and 28 had lethargy. 64%, 70% and 17.9% had symptomatic improvement after treatment respectively. Grade 3–4 toxicities were anaemia 10.6%, neutropenia 2.6%, thrombocytopenia 5.2%, diarrhoea 18.9%, nausea and vomiting 2.7%, infection 5.4% and lethargy 37.8%. The median survival was 9.1 months. Probability of overall survival at 6 months was 58.4% (95% CI = 38.7–73.7%). The median failure-free survival was 4 months. Oxaliplatin and PVI 5FU is an active and well tolerated regimen in patients with heavily pre-treated advanced colorectal cancer. © 2001 Cancer Research Campaig

Survey of oxaliplatin-associated neurotoxicity using an interview-based questionnaire in patients with metastatic colorectal cancer

BACKGROUND: New chemotherapy regimens for patients with colorectal cancer have improved survival, but at the cost of clinical toxicity. Oxaliplatin, an agent used in first-line therapy for metastatic colorectal cancer, causes acute and chronic neurotoxicity. This study was performed to carefully assess the incidence, type and duration of oxaliplatin neurotoxicity. METHODS: A detailed questionnaire was completed after each chemotherapy cycle for patients with metastatic colorectal cancer enrolled in a phase I trial of oxaliplatin and capecitabine. An oxaliplatin specific neurotoxicity scale was used to grade toxicity. RESULTS: Eighty-six adult patients with colorectal cancer were evaluated. Acute neuropathy symptoms included voice changes, visual alterations, pharyngo-laryngeal dysesthesia (lack of awareness of breathing); peri-oral or oral numbness, pain and symptoms due to muscle contraction (spasm, cramps, tremors). When the worst neurotoxicity per patient was considered, grade 1/2/3/4 dysesthesias and paresthesias were seen in 71/12/5/0 and 66/20/7/1 percent of patients. By cycles 3, 6, 9, and 12, oxaliplatin dose reduction or discontinuation was needed in 2.7%, 20%, 37.5% and 62.5% of patients. CONCLUSION: Oxaliplatin-associated acute neuropathy causes a variety of distressing, but transient, symptoms due to peripheral sensory and motor nerve hyperexcitability. Chronic neuropathy may be debilitating and often necessitates dose reductions or discontinuation of oxaliplatin. Patients should be warned of the possible spectrum of symptoms and re-assured about the transient nature of acute neurotoxicity. Ongoing studies are addressing the treatment and prophylaxis of oxaliplatin neurotoxicity

A phase II study of capecitabine plus 3-weekly oxaliplatin as first-line therapy for patients with advanced gastric cancer

Capecitabine plus oxaliplatin every 3 weeks (XELOX regimen) has proven efficacy in patients with colorectal carcinoma. We investigated this combination in patients with previously untreated advanced gastric carcinoma. The study population comprised patients with histologically confirmed nonresectable advanced gastric adenocarcinoma. Patients received intravenous oxaliplatin 130 mg m−2 over 2 h on day 1 plus oral capecitabine 1000 mg m−2 twice daily on days 1–14, every 3 weeks. Patients received a maximum of eight cycles. Twenty evaluable patients (17 men, 3 women) with a median age of 64 years (range 38–75) were enrolled. The overall response rate was 65% (95% confidence interval (CI), 44–86%), with complete responses in two patients and partial responses in 11 patients. Median progression-free survival was 7.5 months (95% CI, 3.2–11.7 months); median overall survival was not reached during the study period. There was no grade 4 and little grade 3 toxicity. The most common haematological adverse event was anaemia (65% of patients) and the most common nonhaematological toxicities were vomiting (65%), neuropathy (60%), diarrhoea (30%), and hand–foot syndrome (20%). In conclusion, XELOX is apparently as effective as triplet combinations and is well tolerated as first-line therapy for advanced gastric carcinoma. We are starting a large multi-institutional phase II study of XELOX in this setting

XELOX (capecitabine plus oxaliplatin) as first-line treatment for elderly patients over 70 years of age with advanced colorectal cancer

The purpose of this phase II trial was to determine the efficacy and safety of the XELOX (capecitabine/oxaliplatin) regimen as first-line therapy in the elderly patients with metastatic colorectal cancer (MCRC). A total of 50 patients with MCRC aged ⩾70 years received oxaliplatin 130 mg m−2 on day 1 followed by oral capecitabine 1000 mg m−2 twice daily on days 1–14 every 3 weeks. Patients with creatinine clearance 30–50 ml min−1 received a reduced dose of capecitabine (750 mg m−2 twice daily). By intent-to-treat analysis, the overall response rate was 36% (95% CI, 28–49%), with three (6%) complete and 15 (30%) partial responses. In total, 18 patients (36%) had stable disease and 14 (28%) progressed. The median times to disease progression and overall survival were 5.8 months (95% CI, 3.9–7.8 months) and 13.2 months (95% CI, 7.6–16.9 months), respectively. Capecitabine was well tolerated: grade 3/4 adverse events were observed in 14 (28%) patients: 11 (22%) diarrhoea, eight (16%) asthenia, seven (14%) nausea/vomiting, three (6%) neutropenia, three (6%) thrombocytopenia, and two (4%) hand–foot syndrome. There was one treatment-related death from diarrhoea and sepsis. In conclusion, XELOX is well tolerated in elderly patients, with respectable efficacy and a meaningful clinical benefit response. Given its ease of administration compared with combinations of oxaliplatin with 5-FU/LV, it represents a good therapeutic option in the elderly