Lapatinib plus capecitabine in treating HER2-positive advanced breast cancer: efficacy, safety, and biomarker results from Chinese patients.
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Overexpression of human epidermal growth factor receptor-2 (HER2) in metastatic breast cancer (MBC) is associated with poor prognosis. This single-arm open-label trial (EGF109491; NCT00508274) was designed to confirm the efficacy and safety of lapatinib in combination with capecitabine in 52 heavily pretreated Chinese patients with HER2-positive MBC. The primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), time to response (TTR), duration of response (DoR), central nervous system (CNS) as first site of relapse, and safety. The results showed that there were 23 patients with partial responses and 7 patients with stable disease, resulting in a CBR of 57.7%. The median PFS was 6.34 months (95% confidence interval, 4.93-9.82 months). The median TTR and DoR were 4.07 months (range, 0.03-14.78 months) and 6.93 months (range, 1.45-9.72 months), respectively. Thirteen (25.0%) patients had new lesions as disease progression. Among them, 2 (3.8%) patients had CNS disease reported as the first relapse. The most common toxicities were palmar-plantar erythrodysesthesia (59.6%), diarrhea (48.1%), rash (48.1%), hyperbilirubinemia (34.6%), and fatigue (30.8%). Exploratory analyses of oncogenic mutations of PIK3CA suggested that of 38 patients providing a tumor sample, baseline PIK3CA mutation status was not associated with CBR (P = 0.639) or PFS (P = 0.989). These data confirm that the lapatinib plus capecitabine combination is an effective and well-tolerated treatment option for Chinese women with heavily pretreated MBC, irrespective of PIK3CA status. (+info)
Capecitabine versus 5-fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results from the X-ACT trial with analysis by age and preliminary evidence of a pharmacodynamic marker of efficacy.
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Celecoxib can prevent capecitabine-related hand-foot syndrome in stage II and III colorectal cancer patients: result of a single-center, prospective randomized phase III trial.
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Determination of sunitinib and its active metabolite N-desethylsunitinib in sweat of a patient.
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Skin reactions are side effects of sunitinib therapy with an adverse impact on quality of life often necessitating dose reductions. For conventional antineoplastic agents, such as doxorubicin, previous studies have indicated a possible relationship between sweat excretion and the development of skin toxicity. However, the determination of sunitinib and its active metabolite in sweat has not yet been reported. A sensitive and accurate method for the determination of sunitinib and its active metabolite N-desethylsunitinib in human sweat was developed using high-performance liquid chromatography coupled to tandem mass spectrometry detection (LC-MS-MS). Sweat samples of a patient treated with sunitinib were collected using Pharmchek Drugs of Abuse patches to determine cumulative amounts of sunitinib and metabolite. Validation of the LC-MS-MS method was performed over a range from 1.0 to 200 ng/patch with good intra- and interassay accuracies for sunitinib and N-desethylsunitinib. Ranges of 76-119 and 7.9-10.5 ng/patch for cumulative secretion of sunitinib and metabolite, respectively, were found in patient samples. To our knowledge, this is the first method for determination of cumulative secretion of sunitinib and N-desethylsunitinib in human sweat samples. Sunitinib and its metabolite were easily detectable in sweat patches of a patient treated with sunitinib. (+info)
Clinical presentation and management of hand-foot skin reaction associated with sorafenib in combination with cytotoxic chemotherapy: experience in breast cancer.
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Adverse event profiles of 5-fluorouracil and capecitabine: data mining of the public version of the FDA Adverse Event Reporting System, AERS, and reproducibility of clinical observations.
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OBJECTIVE: The safety profiles of oral fluoropyrimidines were compared with 5-fluorouracil (5-FU) using adverse event reports (AERs) submitted to the Adverse Event Reporting System, AERS, of the US Food and Drug Administration (FDA). METHODS: After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving 5-FU and oral fluoropyrimidines were analyzed. Standardized official pharmacovigilance tools were used for the quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. RESULTS: Based on 22,017,956 co-occurrences, i.e., drug-adverse event pairs, found in 1,644,220 AERs from 2004 to 2009, it was suggested that leukopenia, neutropenia, and thrombocytopenia were more frequently accompanied by the use of 5-FU than capecitabine, whereas diarrhea, nausea, vomiting, and hand-foot syndrome were more frequently associated with capecitabine. The total number of co-occurrences was not large enough to compare tegafur, tegafur-uracil (UFT), tegafur-gimeracil-oteracil potassium (S-1), or doxifluridine to 5-FU. CONCLUSION: The results obtained herein were consistent with clinical observations, suggesting the usefulness of the FDA's AERS database and data mining methods used, but the number of co-occurrences is an important factor in signal detection. (+info)
Development and validation of a prediction index for hand-foot skin reaction in cancer patients receiving sorafenib.
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