Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients

Schüller, J.; Cassidy, Jim; Dumont, Étienne; Roos, Brigitte; Durston, Sarah; Banken, Ludger; Utoh, Masahiro; Mori, Kazushige; Weidekamm, E.; Reigner, Bruno

doi:10.1007/s002800050043

Cited by 613 publications

(340 citation statements)

References 11 publications

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“…Similar observations had been previously reported in head and neck tumours for patients pretreated for 1 week with UFT before surgery (Tachibana et al, 1987). Higher concentrations of 5-FU in tumours were reported for colorectal cancer patients treated by capecitabine (Schüller et al, 2000). Patients received 1 225 mg m À2 twice daily for 5 -7 days prior to surgery.…”

Section: Dpd Inhibitionsupporting

confidence: 82%

Comparative pharmacology of oral fluoropyrimidines: a focus on pharmacokinetics, pharmacodynamics and pharmacomodulation

2004

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The main purpose of the present review article was to shed light on the different 5-fluorouracil (5-FU) prodrugs by underlining their respective pharmacological features in terms of metabolic activation, dihydropyrimidine dehydrogenase inhibition, pharmacokinetic profile and biomodulation ability. Oral fluoropyrimidines differ particularly as concerns their pharmacokinetic profile and especially in the delivery of circulating 5-FU. More clinical studies need to be performed incorporating tumour predictive markers during oral fluoropyrimidine-based treatment. The new possibilities are to achieve pharmacomodulation of oral fluoropyrimidines, notably for UFT and capecitabine, that open up the prospect of establishing significant novel treatment protocols based on drug combinations.

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Section: Dpd Inhibitionsupporting

confidence: 82%

Comparative pharmacology of oral fluoropyrimidines: a focus on pharmacokinetics, pharmacodynamics and pharmacomodulation

2004

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“…The selective tumour activation of capecitabine has been confirmed in a trial of patients with colorectal cancer (Schüller et al, 2000). Patients were treated with capecitabine 1255 mg m 72 twice daily for 5 to 7 days before surgical resection of their primary tumour or metastatic lesions.…”

mentioning

confidence: 99%

Randomised, phase II trial comparing oral capecitabine (Xeloda®) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines

et al. 2002

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Capecitabine, an oral fluoropyrimidine carbamate, was designed to generate 5-fluorouracil preferentially at the tumour site. This randomised, phase II trial evaluated the efficacy and safety of capecitabine or paclitaxel in patients with anthracyclinepretreated metastatic breast cancer. Outpatients with locally advanced and/or metastatic breast cancer whose disease was unresponsive or resistant to anthracycline therapy were randomised to 3-week cycles of intermittent oral capecitabine (1255 mg m 72 twice daily, days 1 -14, (22 patients)) or a reference arm of i.v. paclitaxel (175 mg m 72 , (20 patients)). Two additional patients were initially randomised to continuous capecitabine 666 mg m 72 twice daily, but this arm was closed following selection of the intermittent schedule for further development. Overall response rate was 36% (95% CI 17 -59%) with capecitabine (including three complete responses) and 26% (95% CI 9 -51%) with paclitaxel (no complete responses). Median time to disease progression was similar in the two treatment groups (3.0 months with capecitabine, 3.1 months with paclitaxel), as was overall survival (7.6 and 9.4 months, respectively). Paclitaxel was associated with more alopecia, peripheral neuropathy, myalgia and neutropenia, whereas typical capecitabine-related adverse events were diarrhoea, vomiting and hand -foot syndrome. Twenty-three per cent of capecitabine-treated patients and 16% of paclitaxel-treated patients achieved a 510% improvement in Karnofsky Performance Status. Oral capecitabine is active in anthracycline-pretreated advanced/ metastatic breast cancer and has a favourable safety profile. Furthermore, capecitabine provides a convenient, patientorientated therapy.

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“…This tumour selectivity is achieved through exploiting the significantly higher activity of thymidine phosphorylase (TP) in many tumour tissues compared with healthy tissue (Miwa et al, 1998;Schuller et al, 2000). The expression of this enzyme is enhanced in tumour areas with poor perfusion, hypoxia, and acidosis, a situation found in most advanced HNSCC.…”

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confidence: 99%

Phase II study of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck

et al. 2005

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We aimed to evaluate the efficacy and safety of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). In total, 37 patients with stage III or IV SCCHN were enrolled on the study. The chemotherapy consisted of two cycles of intravenous cisplatin of 80 mg m À2 on day 1 and oral capecitabine 825 mg m À2 twice daily from day 1 to day 14 at 3-week intervals. The radiotherapy (1.8 -2.0 Gy 1 fraction day À1 to a total dose of 70 -70.2 Gy) was delivered to the primary tumour site and neck. The primary tumour sites were as follows: oral cavity (n ¼ 6), oropharynx (n ¼ 11), hypopharynx (n ¼ 8), larynx (n ¼ 3), nasopharynx (n ¼ 6), and paranasal sinus (n ¼ 3). After the chemoradiotherapy, 29 complete responses (78.4%) and 6 partial responses (16.2%) were confirmed. Grade 3 or 4 neutropenia occurred only in two patients, plus grade 3 febrile neutropenia was observed only in one patient. At a median follow-up duration of 19.8 months, the estimated overall survival and progression-free survival rate at 2-year was 76.8 and 57.9%, respectively. Concurrent chemoradiotherapy with capecitabine and cisplatin was found to be well tolerated and effective in patients with locally advanced SCCHN.

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Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients

Cited by 613 publications

References 11 publications

Comparative pharmacology of oral fluoropyrimidines: a focus on pharmacokinetics, pharmacodynamics and pharmacomodulation

Comparative pharmacology of oral fluoropyrimidines: a focus on pharmacokinetics, pharmacodynamics and pharmacomodulation

Randomised, phase II trial comparing oral capecitabine (Xeloda®) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines

Phase II study of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck

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