Superior Survival With Capecitabine Plus Docetaxel Combination Therapy in Anthracycline-Pretreated Patients With Advanced Breast Cancer: Phase III Trial Results

O’Shaughnessy, Joyce; Miles, David; Vukelja, Svetislava J.; Moiseyenko, Vladimir; Ayoub, Jean-Pierre; Cervantes, Guadalupe; Fumoleau, P.; Jones, Stephen E.; Wy, Lui; Mauriac, L.; Twelves, Chris; Hazel, G. Van; Verma, Shailendra; Leonard, Robert

doi:10.1200/jco.2002.09.002

Cited by 979 publications

(657 citation statements)

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“…The diagnostic and therapeutic summaries of all clin ical records in the department database were screened to select women g iven chemotherapy for metastatic breast cancer between January 1, 2000 and December 31,2004. The following inclusion criteria were applied : female patient, age 18 years or over, breast cancer, delivery of at least one systemic chemotherapy protocol beyond line two (CT3 o r higher) for metastatic disease.…”

Section: Methodsmentioning

confidence: 99%

Usefulness of chemotherapy beyond the second line for metastatic breast cancer: a therapeutic challenge

Vauléon

Mesbah

Laguerre³

et al. 2009

Cancer Chemother Pharmacol

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To cite this version:Elodie Purpose: Several lines of chemotherapy can be proposed for patients with metastatic breast cancer, but beyond the second line, agreement is lacking concerning the most appropriate therapeutic strategy. Methods:We conducted a retrospective analysis of the files of 162 patients, who had received at least three lines of chemotherapy (CT3) for metastatic breast cancer during a 5-year period (2000 to 2004), in order to analy ze management practices and search for factors affecting survival fro m CT3 and predictive factors of nonprogressive disease after CT3.Results: Multivariate analysis identified seven factors which had a positive influence on survival fro m CT3 (SBR grade I, absence of adjuvant hormone therapy, free interval ≥ 2 years, absence of cerebromeningeal metastasis before CT, unique focus at initiat ion of CT3, use of polychemotherapy for CT2, and comp lete res ponse to CT1 or CT2) and two predict ive factors of non-progressive disease (histology and drug group used for CT3).Conclusions: These factors should help determine the appropriate strategy for proposing a third line of chemotherapy.. .

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Section: Methodsmentioning

confidence: 99%

Usefulness of chemotherapy beyond the second line for metastatic breast cancer: a therapeutic challenge

Vauléon

Mesbah

Laguerre³

et al. 2009

Cancer Chemother Pharmacol

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“…Combinations between TP-inducible treatments and TP-targeting therapies seem to have improved response and survival in patients with various types of cancer, e.g. breast cancer (O'Shaughnessy et al, 2002). In the present extended phase-I trial we sought to combine capecitabine, a TP-targeting therapy with the two most potent TP-inducing chemotherapeutics, docetaxel and mitomycin C. Our current findings indicate that capecitabine 1000 mg m À2 orally b.i.d.…”

Section: Discussionmentioning

confidence: 89%

“…In a large phase-III trial the addition of capecitabine to docetaxel resulted in a significant superior survival over single-agent docetaxel in 511 anthracycline-pretreated patients with advanced breast cancer (O'Shaughnessy et al, 2002). This randomised trial revealed that the combination of both drugs provided clear benefits over single-agent docetaxel in terms of objective tumour response rate (42 vs 30%), time to progression (median, 6.1 vs 4.2 months), and overall survival (median, 14.5 vs 11.5 months).…”

mentioning

confidence: 99%

Capecitabine in combination with docetaxel and mitomycin C in patients with pre-treated tumours: results of an extended phase-I trial

et al. 2007

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Preclinical data suggest that the anti-tumour activity of capecitabine is enhanced by taxanes and mitomycin C through up-regulation of thymidine phosphorylase (TP). Here, we studied safety and efficacy of the combination of capecitabine with docetaxel and mitomycin C. Two dose levels (DL) were investigated: capecitabine 1000 mg m À2 b.i.d. on days 1 -14, docetaxel 40 mg m À2 i.v. day 1, mitomycin C 4 or 6 mg m À2 i.v. day 1 (DL I or II). Cycles were repeated every 3 weeks. The primary aim was to determine the dose-limiting toxicities (DLT) during the first two treatment cycles and the maximum tolerated dose (MTD). A total of 46 patients (pts) refractory to standard therapies were enrolled, of whom the majority had gastrointestinal tumours (n ¼ 40). 14 pts had received X3 lines of prior chemotherapy. At DL I, one out of six pts experienced DLT. At DL II, two out of six pts had DLT (mucositis grade 3). Thus, DL I was determined as MTD. Among a total of 37 pts treated on DL I the following toxicities were observed during cycles 1 and 2 (number of patients with grade 1/2/3/4 toxicity; NCI-CTC v. 3.0): anaemia 10/8/3/0, leucocytopenia 4/11/1/2, thrombocytopenia 0/1/ 2/0, diarrhoea 8/1/2/0, stomatitis/mucositis 3/3/1/0, nausea/vomiting 10/2/0/0, and hand-foot skin reaction 5/1/1/0. Of 30 pts who received at least two treatment cycles nine achieved complete or partial remissions, six pts achieved minor remissions, and seven pts had stable disease (tumour control rate 73%). Of note, four out of 10 patients with pancreatic cancer had partial remissions. In conclusion, capecitabine can safely be combined with docetaxel (40 mg m À2 ) and mitomycin C (4 mg m À2 ). The established regimen was well tolerated and the preliminary efficacy data in this heavily pre-treated patients population appears to be promising.

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“…However, the exact mechanistic cause of the TP modulation by the cytotoxics has not been clearly elucidated and indirect effects via the upregulation of TNFa have been advocated (Sawada et al, , 1999. The preclinical findings of supra-additive antitumour effects of combining taxanes and capecitabine have been followed by promising clinical results in breast cancer treatment with a protocol based on a capecitabinedocetaxel combination (O'Shaughnessy et al, 2002). Recent findings suggest that cytochrome P-4502A6 is the major enzyme responsible for the bioactivation process of ftorafur (Ikeda et al, 2000).…”

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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Superior Survival With Capecitabine Plus Docetaxel Combination Therapy in Anthracycline-Pretreated Patients With Advanced Breast Cancer: Phase III Trial Results

Cited by 979 publications

References 17 publications

Usefulness of chemotherapy beyond the second line for metastatic breast cancer: a therapeutic challenge

Usefulness of chemotherapy beyond the second line for metastatic breast cancer: a therapeutic challenge

Capecitabine in combination with docetaxel and mitomycin C in patients with pre-treated tumours: results of an extended phase-I trial

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

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