Abstract
Background
A pilot phase II study was conducted to evaluate the efficacy and safety of the Japanese intermittent regimen of capecitabine (Xeloda®) in patients with advanced or recurrent breast cancer.
Methods
A total of 23 patients who had received no more than one prior chemotherapy regimen received oral 828 mg/m2 capecitabine twice daily for 3 weeks followed by a 1-week rest period. The response to capecitabine was evaluated in 22 patients (one patient ineligible).
Results
The overall response rate was 45.5% (95% CI, 24.4–67.8%), including 1 complete response (4.5%) and 9 patients with partial response (40.9%). A further 7 patients (31.8%) had stable disease. The median duration of response was 7.2 months (range, 3.0–15.8 months) and the median time to progression was 6.4 months (95% CI, 4.1–15.1 months). Treatment-related adverse events ≧ grade 3 were observed in 7 patients (30.1%).
Conclusion
Intermittent capecitabine therapy (828 mg/m2 twice daily for 3 weeks followed by a 1-week rest period) was shown to be effective and well tolerated as second-line treatment for advanced or recurrent breast cancer. The Japanese regimen is worthy of further study in larger numbers of patients in phase II/IIIclinical trials.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Blum JL, Dieras V, Lo Russo PM,et al: Multicenter, Phase II study of capecitabine in taxane-pretreated metastatic breast carcinoma patients.Cancer 92:1759–1768, 2001.
Blum JL, Jones SE, Buzdar AU,et al: Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer.J Clin Oncol 17:485–493, 1999.
Borner MM, Schoffski P, de Wit R,et al: Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial in advanced colorectal cancer.Eur J Cancer 38:349–358, 2002.
Budman DR, Meropol NJ, Reigner B,et al: Preliminary studies of a novel oral fluoropyrimidine carbamate: capecitabine.J Clin Oncol 16:1795–1802, 1998.
Fleming TR: One-sample multiple testing procedure for phase II trials.Biometrics 38:143–151, 1981.
Fumoleau P, Largillier R, Clippe C,et al: Multicentre, phase II study evaluating capecitabine monotherapy in patients with anthracycline and taxanepretreated metastatic breast cancer.Eur J Cancer 40:536–542, 2004.
Ishikawa T, Sekiguchi F, Fukase Y,et al: Positive correlation between the efficacy of capecitabine and doxifluridine and the ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase activities in tumors in human cancer xenografts.Cancer Res 58:685–690, 1998.
Japanese Breast Cancer Society. General Rules for Clinical and Pathological Recording of Breast Cancer, 11th version, July 1992.
Kusama M, Sano M, Ikeda T,et al: A phase II study of Xeloda (capectiabine) in patients with advanced/ metastatic breast carcinoma. The Cooperative Study Group of Capecitabine for Breast Carcinoma.Proc Am Soc Clin Oncol 20:44b, 2001 (Abstr 1924).
Kono A, Hara Y, Sugata S,et al: Activation of 5′-deoxy-5-fluorouridine by thymidine phosphorylase in human tumors.Chem Pharm Bull (Tokyo) 31:175–178, 1983.
Liu G, Franssen E, Fitch MI, Warner E: Patient preferences for oral versus intravenous palliative chemotherapy.J Clin Oncol 15:110–115, 1997.
Miwa M, Ura M, Nishida M,et al: Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumors by enzymes concentrated in human liver and cancer tissue.Eur J Cancer 34:1274–1281, 1998.
National Cancer Institute of Canada. Common Toxicity Criteria Grading System (NCIC-CTC Grading System), revised May 1991.
Niitani H, Kimura K, Saito T,et al: Phase II study of 5′-deoxy-5-fluorouridine (5′-DFUR) in patients with malignant cancer: multi-institutional cooperative study.Gan To Kagaku Ryoho 12:2044–2051, 1985.
Ninomiya Y, Miwa M, Eda H,et al: Comparative antitumor activity and intestinal toxicity of 5′-deoxy-5-flu-orouridine and its prodrug trimethoxybenzoyl-5′-deoxy-5-fluorocutidine.Jpn Cancer Res 81:188–195, 1990.
O’Shaughnessy JA, Blum J, Moiseyenko V,et al: Randomized, open-label, phase II trial of oral capecitabine (Xeloda) vs. a reference arm of intravenous CMF (cyclophosphamide, methotrexate and 5-fluo-rouracil) as first-line therapy for advanced/metastatic breast cancer.Ann Oncol 12:1247–1254, 2001.
O’Shaughnessy J, Miles D, Vukelja S,et al: Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results.Clin Oncol 20:2812–2823, 2002.
Payne SA: A study of quality of life in cancer patients receiving palliative chemotherapy.Soc Sci Med 35:1505–1509, 1992.
Perez EA: Current management of metastatic breast cancer.Semin Oncol 26(Suppl. 12):1–10, 1999.
Reigner B, Blesch K, Weidekamm E: Clinical Pharmacokinetics of capecitabine.Clin Pharmacokinet 40:85–104, 2001.
Saeki T, Takashima S, Terashima S,et al: A Japanese phase I study of continuous oral capecitabine in patients with malignant solid tumors.Int J Clin Oncol 10:51–57, 2005.
Schuller J, Cassidy J, Dumont E,et al: Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients.Cancer Chemother Pharmacol 45:291–297, 2000.
Talbot DC, Moiseyenko V, Van Belle S,et al: Randomised, phase II trial comparing oral capecitabine (Xeloda) with paclitaxel in patients with metastatic/ advanced breast cancer pretreated with anthracy-clines.Br J Cancer 86:1367–1372, 2002.
Watanabe T, Katsumata N, Sasaki Y,et al: A multicenter phase II trial of Xeloda (capecitabine) in patients with docetaxel-refractory advanced/metastatic breast cancer.Proc Am Soc Clin Oncol 20:61b, 2001 (Abstr 1991).
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Saeki, T., Kimura, T., Toi, M. et al. A pilot phase II study of capecitabine in advanced or recurrent breast cancer. Breast Cancer 13, 49–57 (2006). https://doi.org/10.2325/jbcs.13.49
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.2325/jbcs.13.49