Phase II study of oral capecitabine in patients with hormone-refractory prostate cancer

Spicer, James; Plunkett, T A; Somaiah, Navita; Chan, See Ching; Kendall, Anne; Bolunwu, N; Pandha, H.

doi:10.1038/sj.pcan.4500821

Cited by 10 publications

(3 citation statements)

References 31 publications

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“…In many studies, capecitabine alone or combined with other agent was proven to be safe and eVective for advanced CRPC patients (El-Rayes et al 2003;Spicer et al 2005;Ferrero et al 2006;Kolodziej et al 2006;Rodney et al 2006;Vaishampayan et al 2009;Gasent et al 2011). Prednisone was frequently used in such settings.…”

Section: Introductionmentioning

confidence: 96%

Evaluation of oral chemotherapy with capecitabine and cyclophosphamide plus thalidomide and prednisone in prostate cancer patients

Meng¹,

Wang²,

Fan³

et al. 2011

J Cancer Res Clin Oncol

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Section: Introductionmentioning

confidence: 96%

Evaluation of oral chemotherapy with capecitabine and cyclophosphamide plus thalidomide and prednisone in prostate cancer patients

Meng¹,

Wang²,

Fan³

et al. 2011

J Cancer Res Clin Oncol

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“…His PSA normalized, the liver size decreased by 7 cm to a normal size and the liver enzymes and alkaline phosphatase also normalized [ 25 ]. This finding could not be confirmed in phase II studies using capecitabine as a single agent in hormone-refractory prostate cancer patients [ 26 , 27 ]. It was however concluded that combined treatment regimens containing capecitabine should be considered, because capecitabine appeared to modulate tumour biology [ 27 ].…”

Section: Discussionmentioning

confidence: 97%

188Re-HEDP combined with capecitabine in hormone-refractory prostate cancer patients with bone metastases: a phase I safety and toxicity study

Lam

Bosma

Rijk

et al. 2009

Eur J Nucl Med Mol Imaging

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Purpose188Re-HEDP is indicated for the treatment of pain in patients with painful osteoblastic bone metastases, including hormone-refractory prostate cancer patients. Efficacy may be improved by adding chemotherapy to the treatment regimen as a radiation sensitizer. The combination of 188Re-HEDP and capecitabine (Xeloda®) was tested in a clinical phase I study.MethodsPatients with hormone-refractory prostate cancer were treated with capecitabine for 14 days (oral twice daily in a dose escalation regimen with steps of 1/3 of 2,500 mg/m2 per day in cohorts of three to six patients, depending on toxicity). Two days later patients were treated with 37 MBq/kg 188Re-HEDP as an intravenous injection. Six hours after treatment post-therapy scintigraphy was performed. Urine was collected for 8 h post-injection. Follow-up was at least 8 weeks. The primary end-point was to establish the maximum tolerable dose (MTD) of capecitabine when combined with 188Re-HEDP. Secondary end-points included the effect of capecitabine on the biodistribution and pharmacokinetics of 188Re-HEDP.ResultsThree patients were treated in the first and second cohorts, each without unacceptable toxicity. One of six patients in the highest cohort experienced unacceptable toxicity (grade 4 thrombopaenia). The MTD proved to be the maximum dose of 2,500 mg/m2 per day capecitabine. No unexpected toxicity occurred. Capecitabine had no effect on uptake or excretion of 188Re-HEDP.ConclusionCapecitabine may be safely used in combination with 188Re-HEDP in a dose of 2,500 mg/m2 per day and 37 MBq/kg, respectively. Efficacy will be further studied in a phase II study using these dosages.

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“…Cases of hormonerefractory prostate cancer responding to capecitabine have been reported [23]. Spicer and coworkers [24] recently published the results of a phase II trial using capecitabine in advanced prostate cancer. The authors concluded that capecitabine as a single drug had limited antitumor activity, but appeared to modulate tumor biology (prostate-specific antigen decrease) and they Docetaxel-erlotinib-5 0 DFUR prostate cancer Fischel et al 809 considered that further evaluation of combinations containing capecitabine was justified in hormone-refractory prostate cancer [24].…”

Section: Discussionmentioning

confidence: 99%

Synergistic cytotoxic interaction in hormone-refractory prostate cancer with the triple combination docetaxel–erlotinib and 5-fluoro-5′-deoxyuridine

Fischel

Ciccolini²,

Formento³

et al. 2006

Anti-Cancer Drugs

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The current reference treatment of hormone-refractory prostate cancer consists mainly of chemotherapy with docetaxel. To improve the management of advanced prostate cancer, one should examine the benefits of adding other agents to docetaxel. We examined the growth inhibitory effects of a triple combination, including the anti-epidermal growth factor receptor drug erlotinib, docetaxel and 5-fluoro-5'-deoxyuridine (the main intermediary metabolite of capecitabine), on the human prostate cancer cell lines PC3 and DU145, which are both devoid of androgen receptors. Marked synergistic cytotoxic effects were observed with the application of the double combination of erlotinib-5-fluoro-5'-deoxyuridine for both cell lines and to a lesser magnitude with the triple combination. For PC3 cells, all conditions resulted in synergistic interactions. The combination between erlotinib and docetaxel resulted in an approximately 50% reduction in thymidylate synthase activity (the molecular target of 5-fluorodeoxyuridine monophosphate, the active capecitabine anabolite) with an higher impact observed with DU145 cells than with PC3 cells. Neither erlotinib nor docetaxel alone displayed marked effects on thymidine phosphorylase activity (the enzyme that governs at the cellular level the final and crucial step in the activation cascade of capecitabine), in contrast to their combination that resulted in a strong increase in thymidine phosphorylase activity in PC3 cells. These data may serve as a rational basis for setting up clinical trials in advanced prostate cancer combining epidermal growth factor receptor-targeting agents like erlotinib together with docetaxel and capecitabine.

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Phase II study of oral capecitabine in patients with hormone-refractory prostate cancer

Cited by 10 publications

References 31 publications

Evaluation of oral chemotherapy with capecitabine and cyclophosphamide plus thalidomide and prednisone in prostate cancer patients

Evaluation of oral chemotherapy with capecitabine and cyclophosphamide plus thalidomide and prednisone in prostate cancer patients

188Re-HEDP combined with capecitabine in hormone-refractory prostate cancer patients with bone metastases: a phase I safety and toxicity study

Synergistic cytotoxic interaction in hormone-refractory prostate cancer with the triple combination docetaxel–erlotinib and 5-fluoro-5′-deoxyuridine

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