ABSTRACT
BACKGROUND: Capecitabine is an oral, tumor-targeted fluoropyrimidine carbamate with high activity in metastatic breast carcinoma and in paclitaxel-pretreated metastatic breast carcinoma. METHODS: The current multicenter, Phase II trial assessed the efficacy and safety of intermittent oral capecitabine, 1255 mg/m(2) twice daily (2 weeks of treatment followed by a 1-week rest period), in patients with metastatic breast carcinoma in whom prior taxane therapy had failed. All patients had failed treatment or had disease that was refractory to two or three previous chemotherapy regimens, one of which contained a taxane. Nearly all patients (96%) also had received prior anthracycline chemotherapy. Seventy-five patients were recruited at 5 centers, 74 of whom received treatment. RESULTS: The overall response rate was 26%, with response rates of 27% and 20%, respectively, in the subgroups of patients previously pretreated with paclitaxel (n = 47) or docetaxel (n = 27). The median survival was 12.2 months, the median duration of response was 8.3 months, and the median time to disease progression was 3.2 months. The most common treatment-related adverse events (all grades) were hand-foot syndrome (62%), diarrhea (58%), nausea (55%), emesis (37%), and stomatitis (34%). However, the majority were mild to moderate in intensity and only three patients experienced Grade 4 (according to the National Cancer Institute of Canada Common Toxicity criteria) adverse events. The only Grade 3 treatment-related adverse events reported in > or = 10% of the patients were hand-foot syndrome (22%), diarrhea (16%), and stomatitis (12%). Myelosuppression and alopecia were rare, and there were no reported treatment-related deaths. CONCLUSIONS: The results of the current study demonstrate that capecitabine is an effective and well tolerated treatment in patients with taxane-refractory or taxane-failing metastatic breast carcinoma. In addition, it is a convenient, orally administered drug, which makes it an attractive agent for use in outpatient treatment.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Breast Neoplasms/drug therapy , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Paclitaxel/analogs & derivatives , Taxoids , Administration, Oral , Adult , Aged , Antimetabolites, Antineoplastic/administration & dosage , Breast Neoplasms/pathology , Capecitabine , Deoxycytidine/administration & dosage , Docetaxel , Drug Administration Schedule , Female , Fluorouracil/analogs & derivatives , Humans , Middle Aged , Neoplasm Metastasis , Paclitaxel/therapeutic use , Survival Analysis , Treatment FailureABSTRACT
Computer-assisted NDAs (CANDAs) have evolved from an instrument that provides information to regulators to also providing information to internal researchers. They are still not as useful internally during the NDA process as they will be in the future. The portion of CANDA that allows summary, display, and query of the raw data is the most complicated part of the CANDA. Roche's current CANDA system, as well as the challenges in using, documenting, and validating such a system, is described, stressing the features that make it usable in-house. Roche's vision of the future is outlined, covering the strategies, targets, and expected savings.
