Search results and population characteristics Statistical analyses were performed by using the comprehensive meta-analysis program (Version 2, Biostat, Englewood, NJ, USA). A two tailed P value of less than 0.05 was considered statistically significant. We evaluated publication bias using funnel plots and with the Begg and Egger tests. Differences in the incidences between the two groups were assessed using Q statistics. We used a random-effects model to produce a pooled overall estimate for incidence of the adverse outcomes. The assumption of homogeneity was considered invalid for P values less than 0.10. Statistical heterogeneity in results between trials included in the meta-analysis was examined using Cochrane's Q statistic, and inconsistency was quantified with I2 statistic, which estimates the percentage of total variation across studies due to heterogeneity rather than chance. The proportion of patients with those adverse outcomes and 95 % CIs were derived from each trial. The principal summary measures were incidence and corresponding 95 % confidence intervals (CIs) of the following AEs: any, all, or high grade AEs, individual, all or high grade AEs (HFS, diarrhea, fatigue, nausea, vomiting, stomatitis, neutropenia, thrombocytopenia, and anemia), dose reductions, treatment discontinuation and treatment-related deaths. The references of relevant reports were also reviewed manually.
Norton 360 free trial 90 days 2012 full#
Then, full texts of the relevant articles were retrieved to assess eligibility. Independent reviewers (TFN and MS) screened reports that included the key terms by their titles and abstracts for relevance. We did not include trials of capecitabine combined with other agents. They included hand foot syndrome (HFS), diarrhea, fatigue, nausea, vomiting, stomatitis, neutropenia, anemia and thrombocytopenia. We assessed nine individual AEs which were commonly reported in clinical trials. Therefore, we conducted a systematic review and meta-analysis of available clinical trials to compare a safety profile between capecitabine starting dose of 1,000 and 1, 250 mg/m2 bid in breast cancer patients.Ĭlinical trials that met the following criteria were included: (1) phase II and III trials of capecitabine monotherapy at 1,000 or 1,250 mg/m2 bid on day 1 through 14 every 3 weeks for breast cancer patients and (2) reporting events or event rate and sample size for any all (grade 1-4) or high (grade 3-4) grade adverse events (AEs), individual, all or high grade AEs, dose reductions, treatment discontinuation or treatment-related deaths. However, there has been a substantial variation in the incidence of toxicities among clinical trials and there has been no systematic attempt to synthesize these data in order to define the overall risk of toxicities induced by the lower and standard dose capecitabine. Based on this experience, a number of investigators have evaluated capecitabine at a lower starting dose (1,000 mg/m2 bid) and demonstrated similar efficacy to the approved dose and a more favorable side effect profile with an incidence of dose reduction, ranging from 16 to 34% in phase II trials. The main treatment-limiting toxicities at this dosage were hand-and-foot syndrome (HFS also called palmer-plantar erythrodysesthesia) and diarrhea. However, 26%–65% of patients had their dose reduced by at least 20% in these trials. It has also been extensively studied in both pretreated and previously untreated MBC patients and demonstrated efficacy in response rate and progression-free survival (PFS). The FDA has approved capecitabine monotherapy 1,250 mg/m2 twice daily (bid) on days 1–14 followed by a 7-day rest period (14/21) for MBC that is resistant to both paclitaxel and anthracyclines. Capecitabine is one of the most active agents in metastatic breast cancer (MBC).
Given this enzyme is over expressed in tumor compared with normal tissue, 5-FU is preferentially generated within the tumor tissue, conferring relatively selective cytotoxicity to the tumor. Capecitabine is an oral pro-drug that is converted to 5-fluorouracil (5-FU) via a three-step enzymatic process, the final step of which is mediated by thymidine phosphorylase.
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