Capecitabine, an Oral Fluoropyrimidine Carbamate With Substantial Activity in Advanced Colorectal Cancer: Results of a Randomized Phase II Study

Cutsem, Éric Van; Findlay, Michael; Osterwalder, B; Kocha, Walter; Dalley, D.; Pazdur, Richard; Cassidy, Jim; Dirix, Luc; Twelves, Chris; Allman, David; Seitz, Jean‐François; Schölmerich, Jürgen; Burger, Hans Ulrich; Verweij, Jaap

doi:10.1200/jco.2000.18.6.1337

Cited by 294 publications

(145 citation statements)

References 20 publications

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“…The incidence of laboratory abnormalities was very low, despite the high incidence of bone and liver lesions. This safety profile is very similar to that seen in other clinical studies investigating capecitabine (O'Shaughnessy et al, 1998;Blum, 1999;Blum et al, 1999a,b;Aapro, 2000;Van Cutsem et al, 2000).…”

Section: Clinicalsupporting

confidence: 85%

“…During recruitment, data from a randomised, phase II study in colorectal cancer patients led to the selection of the intermittent capecitabine regimen for further clinical development (Van Cutsem et al, 2000), and therefore recruitment to continuous capecitabine treatment in the present study was stopped, creating a two-arm study. The recruitment target was 76 patients or 68 evaluable patients.…”

Section: Patient Demography and Dispositionmentioning

confidence: 99%

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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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Section: Clinicalsupporting

confidence: 85%

Section: Patient Demography and Dispositionmentioning

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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“…Nevertheless, a high incidence of severe neutropenia, associated with greater use of haematopoietic growth factors, is often reported when 5-FU, L-HOP, and CPT-11 are simultaneously combined (Falcone et al, 2002;Souglakos et al, 2002). Hand -foot syndrome, which is frequently described with the use of continuous 5-FU infusions or capecitabine (Van Cutsem et al, 2000), was never observed, possibly because the profile of frequent oral UFT/ LV dosing may resemble that of a repeated mini-bolus (Ho et al, 1998) and the UFT dose (250 m À2 day À1 ) was lower than the 300 -350 mg m À2 day À1 used by other authors. The complete absence of hand -foot syndrome is very promising and a major advantage over similar studies of capecitabine.…”

Section: Discussionmentioning

confidence: 99%

UFT/leucovorin and oxaliplatin alternated with UFT/leucovorin and irinotecan in metastatic colorectal cancer

et al. 2004

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A total of 41 metastatic colorectal cancer (CRC) patients received tegafur/uracil (UFT) þ leucovorin (LV) þ oxaliplatin alternated with UFT/LV þ irinotecan. The overall response rate was 58.5% (95% confidence interval, 42.2 -73.3%), and the median progressionfree survival was 8.8 months. There were no grade 4 toxicities; 12 patients (29%) experienced grade 3 diarrhoea. There were no cases of hand -foot syndrome. This alternating regimen seems to be effective and well tolerated in the first-line treatment of patients with metastatic CRC.

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“…Thus, it is not clear, as is the case with the current clinical protocols, whether prolonged exposure to UFT results in an equivalent TS inhibition rate with or without LV supplementation. On the other hand, Van Cutsem et al (2000) undertook a randomised phase II trial in advanced colorectal cancer patients aimed at selecting the most appropriate capecitabine regimen for testing in phase III studies. Two arms (2 weeks on/1 week off) differed by the presence or not of daily oral LV.…”

Section: Pharmacomodulationmentioning

confidence: 99%

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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Capecitabine, an Oral Fluoropyrimidine Carbamate With Substantial Activity in Advanced Colorectal Cancer: Results of a Randomized Phase II Study

Cited by 294 publications

References 20 publications

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

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

UFT/leucovorin and oxaliplatin alternated with UFT/leucovorin and irinotecan in metastatic colorectal cancer

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

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