Affiliation: University of Leeds
- Trials and tribulations of cytotoxic and targeted breast cancer therapy: a clinical perspective on the next phase of progress. Interview by Sophia Maprayil and Alexandra HemsleyChris Twelves
Level 4, Bexley Wing, St James s University Hospital, Beckett Street, Leeds, LS9 7TF, UK
Expert Rev Anticancer Ther 13:251-5. 2013Interview by Sophia Maprayil and Alexandra Hemsley, Commissioning Editors Chris Twelves is a medical oncologist and leads the Section of Oncology and Clinical Research at Cancer Research UK's Clinical Centre at St James's Hospital, Leeds...
- Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analysesD Alan Anthoney
St James Institute of Oncology, University of Leeds and Leeds Teaching Hospitals Trust, Leeds LS9 7TF, United Kingdom
BMC Cancer 12:536. 2012..A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011...
- Capecitabine versus 5-fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results from the X-ACT trial with analysis by age and preliminary evidence of a pharmacodynamic marker of efficacyC Twelves
University of Leeds and St James s Institute of Oncology Hospital, Leeds Cancer Research UK Centre, Leeds, UK
Ann Oncol 23:1190-7. 2012..This multicenter randomized trial compared oral capecitabine with bolus i.v. 5-fluorouracil (5-FU)/folinic acid (FA) as adjuvant therapy for stage III colon cancer...
- Phase III trials of eribulin mesylate (E7389) in extensively pretreated patients with locally recurrent or metastatic breast cancerChris Twelves
Leeds Institute of Molecular Medicine, St James University Hospital, Leeds, United Kingdom
Clin Breast Cancer 10:160-3. 2010..Tumor assessments are carried out every 8 weeks in Study 305, and every 2 cycles (each of 3 weeks' duration) in Study 301. Safety is also assessed in both studies...
- Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised studyJavier Cortes
Vall d Hebron University Hospital, Vall d Hebron Institute of Oncology, Barcelona, Spain
Lancet 377:914-23. 2011..Eribulin mesilate is a non-taxane microtubule dynamics inhibitor with a novel mode of action. We aimed to compare overall survival of heavily pretreated patients receiving eribulin versus currently available treatments...
- Is oxaliplatin combined with weekly bolus 5-fluorouracil and leucovorin an option for stage II and III colon cancer?Chris Twelves
Cancer Research UK Clinical Centre, University of Leeds, UK
Nat Clin Pract Oncol 5:72-3. 2008
- Erlotinib in combination with capecitabine and docetaxel in patients with metastatic breast cancer: a dose-escalation studyChris Twelves
University of Leeds and St James Hospital, Leeds, United Kingdom
Eur J Cancer 44:419-26. 2008..Pharmacokinetic studies showed that exposure to the three drugs was not reduced when given in combination. These encouraging preliminary results warrant further trials of the combination in MBC...
- Phase II study of the halichondrin B analog eribulin mesylate in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline, a taxane, and capecitabineJavier Cortes
Vall d Hebron University Hospital, Barcelona, Spain
J Clin Oncol 28:3922-8. 2010....
- Capecitabine as adjuvant treatment for stage III colon cancerChris Twelves
University of Leeds and Bradford NHS Hospitals Trust, Leeds, United Kingdom
N Engl J Med 352:2696-704. 2005..The oral fluoropyrimidine capecitabine is an established alternative to bolus fluorouracil plus leucovorin as first-line treatment for metastatic colorectal cancer. We evaluated capecitabine in the adjuvant setting...
- Comparison of outcomes after fluorouracil-based adjuvant therapy for stages II and III colon cancer between 1978 to 1995 and 1996 to 2007: evidence of stage migration from the ACCENT databaseQian Shi
Qian Shi, Axel Grothey, Brian M Bot, and Daniel J Sargent, North Central Cancer Treatment Group, Mayo Clinic, Rochester, MN Thierry Andre, Hopital Saint Antoine, Paris, France Greg Yothers and Michael J O Connell, National Surgical Adjuvant Breast and Bowel Project, Pittsburgh Daniel G Haller, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA Stanley R Hamilton, University of Texas MD Anderson Cancer Center, Houston, TX Brian M Bot, Sage Bionetworks Jacqueline K Benedetti, Southwest Oncology Group Statistical Center, Seattle, WA Eric Van Cutsem, University Hospital Gasthuisberg, Gasthuisberg, Belgium and Chris Twelves, St James s University Hospital, Leeds, United Kingdom
J Clin Oncol 31:3656-63. 2013....
- Scheduling of taxanes: a reviewEmma J Woodward
St James s Institute of Oncology, Leeds, UK
Curr Clin Pharmacol 5:226-31. 2010..In practice, the choice of schedule is a balance between the better tolerability (and possibly efficacy) of weekly treatment balanced against the inconvenience for both the patient and clinic of more frequent visits for chemotherapy...
- Tubulin: an example of targeted chemotherapyJenny Seligmann
Section of Oncology and Clinical Research, Leeds Institute of Molecular Medicine, St James Institute of Oncology, St James University Hospital, Leeds, UK
Future Med Chem 5:339-52. 2013..Agents demonstrating utility in Phase III clinical trials, including eribulin, ixabepilone, cabazitaxel and trastuzumab-DM1 will be highlighted, as well as novel agents currently in development and future directions for MTAs...
- Loading doses for costly cancer biologicals: a cause for concern or tilting at windmills?Ivo M Hennig
Section of Oncology and Clinical Research, Cancer Research UK Clinical Centre, Leeds Institute of Molecular Medicine, University of Leeds and St James s University Hospital, 4th Floor, Bexley Wing, Leeds LS9 7TF, UK
Eur J Cancer 44:1493-6. 2008..Rather, the issue of loading doses should be seen in the broader context of how best to define the optimal dose, schedule and duration of treatment through novel clinical trial designs...
- Clinical grade OK432-activated dendritic cells: in vitro characterization and tracking during intralymphatic deliveryEmma West
Cancer Research UK Clinical Centre, Leeds Institute of Molecular Medicine, Leeds Teaching Hospitals NHS Trust, St James s University Hospital Leeds, UK
J Immunother 32:66-78. 2009..These results show that OK-DC are suitable for clinical use, and that intralymphatic delivery is feasible for localizing cells to sites where optimal priming of innate and adaptive antitumor immunity is likely to occur...
- Potential regional differences for the tolerability profiles of fluoropyrimidinesDaniel G Haller
Abramson Cancer Center at the University of Pennsylvania, Philadelphia, PA, USA
J Clin Oncol 26:2118-23. 2008....
- Docetaxel weekly with metastatic breast cancerChris Twelves
Onkologie 30:407-8. 2007
- Treatment for anthracycline-pretreated metastatic breast cancerJoyce O'Shaughnessy
Baylor Sammons Cancer Center and US Oncology, Dallas, Texas 75246, USA
Oncologist 7:4-12. 2002....
- XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancerJim Cassidy
CRC Department of Oncology, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1DB, United Kingdom
J Clin Oncol 22:2084-91. 2004..The present studies further characterize efficacy and safety of the XELOX regimen...
- Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial resultsJoyce O'Shaughnessy
Baylor Sammons Cancer Center, Dallas, TX 75246, USA
J Clin Oncol 20:2812-23. 2002..This international phase III trial compared efficacy and tolerability of capecitabine/docetaxel therapy with single-agent docetaxel in anthracycline-pretreated patients with MBC...
- Moving forward with capecitabine: a glimpse of the futureLaura Biganzoli
EORTC Investigational Drug Branch for Breast Cancer, Chemotherapy Unit, Institut Jules Bordet, Brussels, Belgium
Oncologist 7:29-35. 2002..Confirmatory studies for many of these combinations and phase III trials versus standard therapy are now warranted...
- Capecitabine plus docetaxel combination therapyShailendra Verma
Department of Medical Oncology, Ottawa Regional Cancer Centre, Ottawa, Canada
Cancer 103:2455-65. 2005..The current study evaluated the cost-effectiveness of the capecitabine/docetaxel combination versus docetaxel monotherapy, comparing the gain in quality-adjusted survival with associated health care costs...
- Optimizing the management of HER2-negative metastatic breast cancer with capecitabine (Xeloda)Robert Leonard
South Wales Cancer Institute, Swansea, UK
Semin Oncol 31:21-8. 2004..In summary, the treatment of MBC will always need to be individualized, but a large body of evidence indicates that capecitabine, whether alone or in combination, can be offered to women early in the disease course...
- Assessment of the validity of a population pharmacokinetic model for epirubicinLorraine D Ralph
Division of Cardiovascular and Medical Sciences, University of Glasgow, Western Infirmary, Glasgow, UK
Br J Clin Pharmacol 62:47-55. 2006..The aim of this study was to evaluate a population model for epirubicin clearance using internal and external validation techniques...
- Capecitabine (Xeloda): from the laboratory to the patient's homeGeorge Pentheroudakis
Department of Medical Oncology, Beatson Oncology Centre, Western Infirmary, Dumbarton Road, Glasgow G11 6NT, Scotland, UK
Clin Colorectal Cancer 2:16-23. 2002..As a home-based outpatient regimen, capecitabine represents a safe and effective advance in modern drug development...
- Clinical pharmacology of the novel marine-derived anticancer agent Ecteinascidin 743 administered as a 1- and 3-h infusion in a phase I studyCharlotte Van Kesteren
Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute Slotervaart Hospital, Amsterdam, The Netherlands
Anticancer Drugs 13:381-93. 2002..Administration of 1650 microg/m(2) ET-743 over 3 h seemed clinically feasible; pharmacokinetics were linear with this schedule. Hepatic and hematological toxicities correlated with exposure to ET-743...
- A population model of epirubicin pharmacokinetics and application to dosage guidelinesLorraine D Ralph
Clinical Pharmacology Section, Division of Cardiovascular and Medical Sciences, University of Glasgow, North Glasgow University Hospitals NHS Trust, Glasgow, UK
Cancer Chemother Pharmacol 52:34-40. 2003..To use a population approach to identify readily available clinical or biochemical characteristics that influence the pharmacokinetics of epirubicin and to develop new dosage guidelines based on these results...
- A phase I study of ZD0473 combined with paclitaxel for the treatment of solid malignanciesChris Twelves
Cancer Research UK Department of Medical Oncology, Beatson Laboratories, University of Glasgow, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK
Cancer Chemother Pharmacol 52:277-81. 2003..The aim of this open-label phase I study was to determine the maximum tolerated dose (MTD), safety, and antitumour activity of ZD0473 followed by paclitaxel in patients with refractory solid malignancies...
- Phase I pharmacological and bioavailability study of oral diflomotecan (BN80915), a novel E-ring-modified camptothecin analogue in adults with solid tumorsHans Gelderblom
Department of Medical Oncology, Erasmus MC Daniel den Hoed, 3008 AE Rotterdam, The Netherlands
Clin Cancer Res 9:4101-7. 2003..This Phase I study was performed to assess the feasibility of the administration of oral diflomotecan, to determine the maximum-tolerated, dose its bioavailability, and to explore the pharmacokinetics...
- Randomized, controlled trial investigating short-term health-related quality of life with doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer: European Organization for ReAndrew Bottomley
Quality of Life Unit, European Organization for Research and Treatment of Cancer Data Center, Insitut Jules Bordet, Brussels, Belgium
J Clin Oncol 22:2576-86. 2004..To compare health-related quality of life (HRQOL) in patients with metastatic breast cancer receiving the combination of doxorubicin and paclitaxel (AT) or doxorubicin and cyclophosphamide (AC) as first-line chemotherapy treatment...
- Phase I study and pharmacokinetic of CHS-828, a guanidino-containing compound, administered orally as a single dose every 3 weeks in solid tumours: an ECSG/EORTC studyAlain Ravaud
Department of Medicine, Institut Bergonie, Bordeaux, France
Eur J Cancer 41:702-7. 2005..The pharmacokinetics of CHS 828 showed large variations both between and within patients. No objective responses were seen. A dose of 420 mg of CHS 828 administered every 3 weeks is the recommended dose, while 500 mg is the MTD...
- Population pharmacokinetics and pharmacodynamics of doxorubicin and cyclophosphamide in breast cancer patients: a study by the EORTC-PAMM-NDDGMarkus Joerger
Department of Pharmacy and Pharmacology, Netherlands Cancer Institute Slotervaart Hospital, Amsterdam, The Netherlands
Clin Pharmacokinet 46:1051-68. 2007..To investigate the population pharmacokinetics and pharmacodynamics of doxorubicin and cyclophosphamide in breast cancer patients...
- Phase I and pharmacodynamic trial of the DNA methyltransferase inhibitor decitabine and carboplatin in solid tumorsKim Appleton
Centre for Oncology and Applied Pharmacology, Glasgow University, Cancer Research UK Beatson Laboratories, Glasgow, United Kingdom
J Clin Oncol 25:4603-9. 2007..We designed a clinical study to determine the feasibility of delivering a dose of decitabine, combined with carboplatin, that would be capable of producing equivalent biologic effects in patients with solid tumors...
- Phase I study of OSI-7904L, a novel liposomal thymidylate synthase inhibitor in patients with refractory solid tumorsGernot Beutel
Department of Hematology, Hemostaseology and Oncology, Hannover Medical School, Hannover, Germany
Clin Cancer Res 11:5487-95. 2005..This phase I study was done to establish the safety, tolerability, maximum tolerated dose, recommended dose, and pharmacokinetics of OSI-7904L in patients with advanced solid tumors refractory to standard therapy...
- Effect of renal impairment on the pharmacokinetics and tolerability of capecitabine (Xeloda) in cancer patientsChristopher Poole
CRC Institute for Cancer Research, University of Birmingham, Birmingham, UK
Cancer Chemother Pharmacol 49:225-34. 2002..Capecitabine (Xeloda) is an orally administered precursor of 5'-deoxy-5-fluorouridine (5'-DFUR), which is preferentially activated to 5-fluorouracil (5-FU) in tumors...