Chris Twelves

Interview 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...

..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...

..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...

..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...

..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 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...

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..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...

..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...

..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...

..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...

..This international phase III trial compared efficacy and tolerability of capecitabine/docetaxel therapy with single-agent docetaxel in anthracycline-pretreated patients with MBC...

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..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...

..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...

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..The present studies further characterize efficacy and safety of the XELOX regimen...

..Confirmatory studies for many of these combinations and phase III trials versus standard therapy are now warranted...

..To investigate the population pharmacokinetics and pharmacodynamics of doxorubicin and cyclophosphamide in breast cancer patients...

..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...

..As a home-based outpatient regimen, capecitabine represents a safe and effective advance in modern drug development...

..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...

..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...

..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...

..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...

..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...

..The main toxicities are rash, pruritis, lethargy, stomatitis, and myelosuppression. Observed toxicities were predictable and characteristic for TSIs...

..CONCLUSIONS: The results of internal validation of population pharmacokinetic models should be interpreted with caution, especially when the dataset is relatively small...

..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...

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