%0 Journal Article
%~ PubMed
%A Ngan, Samuel Y
%A Burmeister, Bryan
%A Fisher, Richard J
%A Solomon, Michael
%A Goldstein, David
%A Joseph, David
%A Ackland, Stephen P
%A Schache, David
%A McClure, Bev
%A McLachlan, Sue-Anne
%A McKendrick, Joseph
%A Leong, Trevor
%A Hartopeanu, Cris
%A Zalcberg, John
%A Mackay, John
%T Randomized Trial of Short-Course Radiotherapy Versus Long-Course Chemoradiation Comparing Rates of Local Recurrence in Patients With T3 Rectal Cancer: Trans-Tasman Radiation Oncology Group Trial 01.04.
%B Journal of Clinical Oncology
%D 2012
%C United States
%I American Society of Clinical Oncology
%V 30
%N 31
%P 3827-3833
%@ 1527-7755
%X 
%Z FOR Codes: 111204


%0 Journal Article
%A Cameron, Andrew
%A Sjoquist, Katrin
%A Zalcberg, John
%T Controversies in oesophagogastric cancer
%B Cancer Forum
%D 2011
%C Australia
%I Cancer Council Australia
%V 35
%N 3
%P 139-141
%@ 0311-306X
%X 
%Z FOR Codes: 111204


%0 Journal Article
%~ PubMed
%A Sjoquist, Katrin M
%A Burmeister, Bryan H
%A Smithers, B Mark
%A Zalcberg, John R
%A Simes, R John
%A Barbour, Andrew
%A Gebski, Val
%A , for the Australasian Gastro-Intestinal Trials Group
%T Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis.
%B The lancet oncology
%D 2011
%C United Kingdom
%I The Lancet Publishing Group
%V 12
%N 7
%P 681-92
%@ 1474-5488
%X In a previous meta-analysis, we identified a survival benefit from neoadjuvant chemotherapy or chemoradiotherapy before surgery in patients with resectable oesophageal carcinoma. We updated this meta-analysis with results from new or updated randomised trials presented in the past 3 years. We also compared the benefits of preoperative neoadjuvant chemotherapy compared with neoadjuvant chemoradiotherapy.
%Z FOR Codes: 111209 111205 111208


%0 Book Section
%A Field, Kathryn
%A Zalcberg, John
%T Chemotherapy: Metastatic Disease
%B Rectal Cancer: International Perspectives on Multimodality Management
%D 2010
%C United States
%I Springer Science+Business Media
%V 
%N 
%P 189-222
%@ 9781607615668
%E Czito, Brian G
%E Willett, Christopher G
%X 
%Z FOR Codes: 111205


%0 Journal Article
%~ PubMed
%A Michael, M
%A Price, T
%A Ngan, S Y
%A Ganju, V
%A Strickland, A H
%A Muller, A
%A Khamly, K
%A Milner, A D
%A Dilulio, J
%A Matera, A
%A Zalcberg, J R
%A Leong, T
%T A phase I trial of Capecitabine+Gemcitabine with radical radiation for locally advanced pancreatic cancer.
%B British journal of cancer
%D 2009
%C United Kingdom
%I Nature Publishing Group
%V 100
%N 1
%P 37-43
%@ 0007-0920
%X Standard chemoradiotherapy with infusional 5FU for locally advanced pancreatic cancer (LAPC) has limited efficacy in this disease. The combination of Capecitabine (Cap) and Gemcitabine (Gem) are synergistic and are potent radiosensitisers. The aim of this phase I trial was thus to determine the highest administered dose of the Cap plus Gem combination with radical radiotherapy (RT) for LAPC. Patients had LAPC, adequate organ function, ECOG PS 0-1. During RT, Gem was escalated from 20-50 mg m(-2) day(-1) (twice per week), and Cap 800-2000 mg m(-2) day(-1) (b.i.d, days 1-5 of each week). Radiotherapy 50.4 Gy/28 fractions/5.5 weeks, using 3D-conformal techniques. Three patients were entered to each dose level (DL). Dose-limiting toxicity(s) (DLTs) were based on treatment-related toxicities. Twenty patients were accrued. Dose level (DL) 1: Cap/Gem; 800/20 mg m(-2) day(-1) (3 patients), DL2: 1000/20 (12 patients), DL3: 1300/30 (5 patients). Dose-limiting toxicities were observed in DL3; grade 3 dehydration (1 patient) and grade 3 diarrhoea and dehydration (1 patient). Dose level 2 was the recommend phase 2 dose. Disease control rate was 75%: PR=15%, SD=60%. Median overall survival was 11.2 months. The addition of Cap and Gem to radical RT was feasible and active and achieved at relatively low doses.
%Z FOR Codes: 111208


%0 Journal Article
%~ PubMed
%A Au, Heather-Jane
%A Karapetis, Christos S
%A O'Callaghan, Chris J
%A Tu, Dongsheng
%A Moore, Malcolm J
%A Zalcberg, John R
%A Kennecke, Hagen
%A Shapiro, Jeremy D
%A Koski, Sheryl
%A Pavlakis, Nick
%A Charpentier, Danielle
%A Wyld, David
%A Jefford, Michael
%A Knight, Gregory J
%A Magoski, Nadine M
%A Brundage, Michael D
%A Jonker, Derek J
%T Health-related quality of life in patients with advanced colorectal cancer treated with cetuximab: overall and KRAS-specific results of the NCIC CTG and AGITG CO.17 Trial.
%B Journal of Clinical Oncology
%D 2009
%C United States
%I American Society of Clinical Oncology
%V 27
%N 11
%P 1822-1828
%@ 1527-7755
%X PURPOSE: National Cancer Institute of Canada Clinical Trials Group CO.17 demonstrated the antiepidermal growth factor receptor (anti-EGFR) monoclonal antibody cetuximab improves overall and progression-free survival in patients with advanced, chemotherapy-refractory colorectal cancer (CRC), particularly in patients with wild-type KRAS tumors. This article reports the health-related quality-of-life (HRQL) outcomes from CO.17. PATIENTS AND METHODS: Patients (N = 572) with pretreated EGFR-detectable advanced CRC were randomly assigned to cetuximab and best supportive care (BSC) or to BSC alone. HRQL primary end points assessed by the EORTC QLQ-C30 were physical function (PF) and global health status (GHS); mean changes from baseline to 8 and 16 weeks were assessed. Post hoc analysis by KRAS mutation status was performed. RESULTS: Questionnaire compliance was 94% at baseline, but it declined differentially (67% v 47% for cetuximab v BSC at 16 weeks). PF change scores were -3.9 for cetuximab and -8.6 for BSC (P = .046) at 8 weeks and were -5.9 and -12.5 for cetuximab and BSC, respectively, (P = .027) at 16 weeks. GHS change scores were -0.5 and -7.1 (P = .008) at 8 weeks and were -3.6 and -15.2 (P = .008) at 16 weeks for cetuximab and BSC, respectively. In patients who had tumors with wild-type KRAS status, cetuximab resulted in less PF deterioration at 8 weeks (-0.7 v -7.2; P = .11) and 16 weeks (-3.4 v -13.8; P = .008) compared with BSC. Patients with wild-type status who received cetuximab experienced improved GHS at 8 weeks, whereas patients who received BSC alone deteriorated (3.2 v -7.7; P = .002). Cetuximab preserved GHS at 16 weeks (-0.2 v -18.1; P < .001). No significant differences were noted between study arms for patients with mutated KRAS tumors. CONCLUSION: Cetuximab offers important HRQL and survival benefits for pretreated patients with advanced, wild-type KRAS CRC.
%Z FOR Codes: 111204


%0 Journal Article
%~ Isi
%A Mittmann, N.
%A Au, H. J.
%A Tu, D. S.
%A O'Callaghan, C. J.
%A Isogai, P. K.
%A Karapetis, C. S.
%A Zalcberg, J. R.
%A Evans, W. K.
%A Moore, M. J.
%A Siddiqui, J.
%A Findlay, B.
%A Colwell, B.
%A Simes, J.
%A Gibbs, P.
%A Links, M.
%A Tebbutt, N. C.
%A Jonker, D. J.
%T Prospective Cost-Effectiveness Analysis of Cetuximab in Metastatic Colorectal Cancer: Evaluation of National Cancer Institute of Canada Clinical Trials Group CO.17 Trial
%B Journal of the National Cancer Institute
%D 2009
%C United Kingdom, United States, Netherlands
%I Oxford University Press
%V 101
%N 
%P 1182-1192
%@ 1460-2105
%X 
%Z FOR Codes: 111205 140208


%0 Journal Article
%~ PubMed
%A Karapetis, Christos S
%A Khambata-Ford, Shirin
%A Jonker, Derek J
%A O'Callaghan, Chris J
%A Tu, Dongsheng
%A Tebbutt, Niall C
%A Simes, R John
%A Chalchal, Haji
%A Shapiro, Jeremy D
%A Robitaille, Sonia
%A Price, Timothy J
%A Shepherd, Lois
%A Au, Heather-Jane
%A Langer, Christiane
%A Moore, Malcolm J
%A Zalcberg, John R
%T K-ras mutations and benefit from cetuximab in advanced colorectal cancer.
%B The New England journal of medicine
%D 2008
%C United States
%I Massachusetts Medical Society
%V 359
%N 17
%P 1757-65
%@ 1533-4406
%X Treatment with cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor, improves overall and progression-free survival and preserves the quality of life in patients with colorectal cancer that has not responded to chemotherapy. The mutation status of the K-ras gene in the tumor may affect the response to cetuximab and have treatment-independent prognostic value.
%Z FOR Codes: 111204


%0 Journal Article
%~ PubMed
%A Van Cutsem, E
%A Dicato, M
%A Haustermans, K
%A Arber, N
%A Bosset, J-F
%A Cunningham, D
%A De Gramont, A
%A Diaz-Rubio, E
%A Ducreux, M
%A Goldberg, R
%A Glynne-Jones, R
%A Haller, D
%A Kang, Y-K
%A Kerr, D
%A Labianca, R
%A Minsky, B D
%A Moore, M
%A Nordlinger, B
%A Rougier, P
%A Scheithauer, W
%A Schmoll, H-J
%A Sobrero, A
%A Tabernero, J
%A Tempero, M
%A Van de Velde, C
%A Zalcberg, J
%T The diagnosis and management of rectal cancer: expert discussion and recommendations derived from the 9th World Congress on Gastrointestinal Cancer, Barcelona, 2007.
%B Annals of oncology : official journal of the European Society for Medical Oncology / ESMO
%D 2008
%C United Kingdom
%I Oxford University Press
%V 19 Suppl 6
%N 
%P vi1-8
%@ 1569-8041
%X Knowledge of the biology and management of rectal cancer continues to improve. A multidisciplinary approach to a patient with rectal cancer by an experienced expert team is mandatory, to assure optimal diagnosis and staging, surgery, selection of the appropriate neo-adjuvant and adjuvant strategy and chemotherapeutic management. Moreover, optimal symptom management also requires a dedicated team of health care professionals. The introduction of total mesorectal excision has been associated with a decrease in the rate of local failure after surgery. High quality surgery and the achievement of pathological measures of quality are a prerequisite to adequate locoregional control. There are now randomized data in favour of chemoradiotherapy or short course radiotherapy in the preoperative setting. Preoperative chemoradiotherapy is more beneficial and has less toxicity for patients with resectable rectal cancer than postoperative chemoradiotherapy. Furthermore chemoradiotherapy leads also to downsizing of locally advanced rectal cancer. New strategies that decrease the likelihood of distant metastases after initial treatment need be developed with high priority. Those involved in the care for patients with rectal cancer should be encouraged to participate in well-designed clinical trials, to increase the evidence-based knowledge and to make further progress. Health care workers involved in the care of rectal cancer patients should be encouraged to adopt quality control processes leading to increased expertise.
%Z FOR Codes: 111202 111204


%0 Journal Article
%~ PubMed
%A Jonker, Derek J
%A O'Callaghan, Chris J
%A Karapetis, Christos S
%A Zalcberg, John R
%A Tu, Dongsheng
%A Au, Heather-Jane
%A Berry, Scott R
%A Krahn, Marianne
%A Price, Timothy
%A Simes, R John
%A Tebbutt, Niall C
%A van Hazel, Guy
%A Wierzbicki, Rafal
%A Langer, Christiane
%A Moore, Malcolm J
%T Cetuximab for the Treatment of Colorectal Cancer.
%B The New England journal of medicine
%D 2007
%C USA
%I Massachusetts Medical Society
%V 357
%N 20
%P 2040-2048
%@ 1533-4406
%X BACKGROUND: Cetuximab, an IgG1 chimeric monoclonal antibody against epidermal growth factor receptor (EGFR), has activity against colorectal cancers that express EGFR. METHODS: From December 2003 to August 2005, 572 patients who had colorectal cancer expressing immunohistochemically detectable EGFR and who had been previously treated with a fluoropyrimidine, irinotecan, and oxaliplatin or had contraindications to treatment with these drugs underwent randomization to an initial dose of 400 mg of cetuximab per square meter of body-surface area followed by a weekly infusion of 250 mg per square meter plus best supportive care (287 patients) or best supportive care alone (285 patients). The primary end point was overall survival. RESULTS: In comparison with best supportive care alone, cetuximab treatment was associated with a significant improvement in overall survival (hazard ratio for death, 0.77; 95% confidence interval [CI], 0.64 to 0.92; P=0.005) and in progression-free survival (hazard ratio for disease progression or death, 0.68; 95% CI, 0.57 to 0.80; P<0.001). These benefits were robust after adjustment in a multivariable Cox proportional-hazards model. The median overall survival was 6.1 months in the cetuximab group and 4.6 months in the group assigned to supportive care alone. Partial responses occurred in 23 patients (8.0%) in the cetuximab group but in none in the group assigned to supportive care alone (P<0.001); the disease was stable in an additional 31.4% of patients assigned to cetuximab and in 10.9% of patients assigned to supportive care alone (P<0.001). Quality of life was better preserved in the cetuximab group, with less deterioration in physical function and global health status scores (both P<0.05). Cetuximab treatment was associated with a characteristic rash; a rash of grade 2 or higher was strongly associated with improved survival (hazard ratio for death, 0.33; 95% CI, 0.22 to 0.50; P<0.001). The incidence of any adverse event of grade 3 or higher was 78.5% in the cetuximab group and 59.1% in the group assigned to supportive care alone (P<0.001). CONCLUSIONS: Cetuximab improves overall survival and progression-free survival and preserves quality-of-life measures in patients with colorectal cancer in whom other treatments have failed. (ClinicalTrials.gov number, NCT00079066.) Copyright 2007 Massachusetts Medical Society.
%Z FOR Codes:


%0 Journal Article
%~ PubMed
%A Debiec-Rychter, Maria
%A Sciot, Raf
%A Le Cesne, Axel
%A Schlemmer, Marcus
%A Hohenberger, Peter
%A van Oosterom, Allan T
%A Blay, Jean-Yves
%A Leyvraz, Serge
%A Stul, Michel
%A Casali, Paolo G
%A Zalcberg, John
%A Verweij, Jaap
%A Van Glabbeke, Martine
%A Hagemeijer, Anne
%A Judson, Ian
%A , EORTC Soft Tissue and Bone Sarcoma Group
%A , Italian Sarcoma Group
%A , Australasian GastroIntestinal Trials Group
%T KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours.
%B European Journal of Cancer
%D 2006
%C United Kingdom
%I Pergamon
%V 42
%N 8
%P 1093-1103
%@ 0959-8049
%X A recent randomized EORTC phase III trial, comparing two doses of imatinib in patients with advanced gastrointestinal stromal tumours (GISTs), reported dose dependency for progression-free survival. The current analysis of that study aimed to assess if tumour mutational status correlates with clinical response to imatinib. Pre-treatment samples of GISTs from 377 patients enrolled in phase III study were analyzed for mutations of KIT or PDGFRA by combination of D-HPLC and direct sequencing of tumour genomic DNA. Mutation types were correlated with patients'' survival data. The presence of exon 9-activating mutations in KIT was the strongest adverse prognostic factor for response to imatinib, increasing the relative risk of progression by 171% (P<0.0001) and the relative risk of death by 190% (P<0.0001) when compared with KIT exon 11 mutants. Similarly, the relative risk of progression was increased by 108% (P<0.0001) and the relative risk of death by 76% (P=0.028) in patients without detectable KIT or PDGFRA mutations. In patients whose tumours expressed an exon 9 KIT oncoprotein, treatment with the high-dose regimen resulted in a significantly superior progression-free survival (P=0.0013), with a reduction of the relative risk of 61%. We conclude that tumour genotype is of major prognostic significance for progression-free survival and overall survival in patients treated with imatinib for advanced GISTs. Our findings suggest the need for differential treatment of patients with GISTs, with KIT exon 9 mutant patients benefiting the most from the 800 mg daily dose of the drug.
%Z FOR Codes: 111205


%0 Journal Article
%~ PubMed
%A Michael, Michael
%A Thompson, Mick
%A Hicks, Rod J
%A Mitchell, Paul L
%A Ellis, Andrew
%A Milner, Alvin D
%A Di Iulio, Julia
%A Scott, Andrew M
%A Gurtler, Volker
%A Hoskins, Janelle M
%A Clarke, Stephen J
%A Tebbut, Niall C
%A Foo, Kian
%A Jefford, Michael
%A Zalcberg, John R
%T Relationship of Hepatic Functional Imaging to Irinotecan Pharmacokinetics and Genetic Parameters of Drug Elimination.
%B Journal of clinical oncology : official journal of the American Society of Clinical Oncology
%D 2006
%C US
%I American Society of Clinical Oncology
%V 24
%N 26
%P 4228-35
%@ 0732-183X
%X The marked variability of irinotecan (Ir) clearance warrants individualized dosing based on hepatic drug handling. The aims of this trial were to identify parameters from functional hepatic nuclear imaging (HNI) that correlate with (1) Ir pharmacology, and (2) single-nucleotide polymorphisms (SNPs) for the ABCB1 (P-glycoprotein) and UGT-1A1 genes, known to influence Ir handling.
%Z FOR Codes: 110502