Abstract:This study puts forward new arguments for the treatment of elderly cancer patients who could benefit from capecitabine chemotherapy with acceptable toxicity.
“…However, no influence of age on the PK of 5-FU or other metabolites has been shown [ 96 ]. Although the impact of FBAL plasma concentrations on clinical toxicity remains unclear, clinically-relevant effects are not expected [ 97 , 98 , 99 , 100 , 101 ]. In one moderate-sized PK study, a lower capecitabine clearance in elderly patients was found ( n = 29), which the authors attributed to the overall number of women included.…”
Section: Resultsmentioning
confidence: 99%
“…This was supported by a population PK analysis study including 20 elderly patients, compared to PK data of 40 younger patients from two previous clinical trials, showing no effect of age on the clearance of capecitabine and its metabolites. Although a difference in absorption by age was documented, the authors reported this as not having clinical relevance [ 101 ]. According to the drug’s SmPC, capecitabine should be used cautiously in elderly patients.…”
Background: Elderly patients receiving anticancer drugs may have an increased risk to develop treatment-related toxicities compared to their younger peers. However, a potential pharmacokinetic (PK) basis for this increased risk has not consistently been established yet. Therefore, the objective of this study was to systematically review the influence of age on the PK of anticancer agents frequently administered to elderly breast cancer patients. Methods: A literature search was performed using the PubMed electronic database, Summary of Product Characteristics (SmPC) and available drug approval reviews, as published by EMA and FDA. Publications that describe age-related PK profiles of selected anticancer drugs against breast cancer, excluding endocrine compounds, were selected and included. Results: This review presents an overview of the available data that describe the influence of increasing age on the PK of selected anticancer drugs used for the treatment of breast cancer. Conclusions: Selected published data revealed differences in the effect and magnitude of increasing age on the PK of several anticancer drugs. There may be clinically-relevant, age-related PK differences for anthracyclines and platina agents. In the majority of cases, age is not a good surrogate marker for anticancer drug PK, and the physiological state of the individual patient may better be approached by looking at organ function, Charlson Comorbidity Score or geriatric functional assessment.
“…However, no influence of age on the PK of 5-FU or other metabolites has been shown [ 96 ]. Although the impact of FBAL plasma concentrations on clinical toxicity remains unclear, clinically-relevant effects are not expected [ 97 , 98 , 99 , 100 , 101 ]. In one moderate-sized PK study, a lower capecitabine clearance in elderly patients was found ( n = 29), which the authors attributed to the overall number of women included.…”
Section: Resultsmentioning
confidence: 99%
“…This was supported by a population PK analysis study including 20 elderly patients, compared to PK data of 40 younger patients from two previous clinical trials, showing no effect of age on the clearance of capecitabine and its metabolites. Although a difference in absorption by age was documented, the authors reported this as not having clinical relevance [ 101 ]. According to the drug’s SmPC, capecitabine should be used cautiously in elderly patients.…”
Background: Elderly patients receiving anticancer drugs may have an increased risk to develop treatment-related toxicities compared to their younger peers. However, a potential pharmacokinetic (PK) basis for this increased risk has not consistently been established yet. Therefore, the objective of this study was to systematically review the influence of age on the PK of anticancer agents frequently administered to elderly breast cancer patients. Methods: A literature search was performed using the PubMed electronic database, Summary of Product Characteristics (SmPC) and available drug approval reviews, as published by EMA and FDA. Publications that describe age-related PK profiles of selected anticancer drugs against breast cancer, excluding endocrine compounds, were selected and included. Results: This review presents an overview of the available data that describe the influence of increasing age on the PK of selected anticancer drugs used for the treatment of breast cancer. Conclusions: Selected published data revealed differences in the effect and magnitude of increasing age on the PK of several anticancer drugs. There may be clinically-relevant, age-related PK differences for anthracyclines and platina agents. In the majority of cases, age is not a good surrogate marker for anticancer drug PK, and the physiological state of the individual patient may better be approached by looking at organ function, Charlson Comorbidity Score or geriatric functional assessment.
“…The analytes were quantitatively measured by this fully validated UHPLC-MS/MS method in the plasma. As a result, apparent differences of drug concentrations in plasma were found in Cap and its metabolites in absorption and metabolism processes, and several studies also reported these differences [16–20]. The drug exposure in vivo has a close relationship with the treatment efficacy and/or side effects, and it was still the promising biomarker for the clinical prognosis.…”
Colorectal cancer is the most common critical disease both in the developed and developing countries. Capecitabine, which has served in clinical practice at least for 10 years, is a first-line antidigestive tract cancer drug for its better efficacy, patient compliance, and lower side effects. An ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method has been developed and completely validated for simultaneous determination of capecitabine and its five metabolites in human plasma from colorectal cancer patients after administration of capecitabine tablet. One-step liquid-liquid extraction was successfully applied using ethyl acetate and isopropanol (19 : 1, V : V) for sample pretreatment. Chromatographic separation was achieved within 5 min based on an Atlantis T3-C18 column (3.0 µm, 2.1 × 100 mm) with gradient elution using mobile phases consisting of 0.0075% formic acid in water (pH 4) and in acetonitrile, and the flow rate was 0.3 mL/min. Linear range was approximately 20.0–5000.0 ng/mL for all analytes. Linear correlation coefficients were >0.99 for all regression curves. The intraday and interday accuracy and precision of the method were within ±15.0% and less than 15.0%, respectively. The mean recovery and matrix effect as well as stability of all the analytes ranged from 59.27% to 90.15% and from 74.84% to 114.48% as well as within ±15.0%. This simple, rapid, and sensitive method was successfully applied in 42 sparse clinical samples to verify its practicability.
“…These results suggested that the XLA patient had a slower ability to absorb Cap and increased thymidine phosphorylase (TYMP) activity. Since both low 5′-DFUR levels and induced TYMP activity are negatively associated with Cap-related toxicity [21, 22] and this patient did not show any sign of DRT, the original chemotherapy plan was not adjusted. Fig.…”
Background
X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by germline mutations in the Bruton tyrosine kinase (BTK) gene on X chromosome. These mutations disturb B-cell development, decrease immunoglobulin levels, increase susceptibility to infection or neoplasms, and increase the risk of developing colorectal cancer (CRC). For occasional cases of CRC have been reported in XLA patients, low levels of B lymphocytes and immunoglobulins induced by congenital immune disorder make them more susceptible to drug-related toxicities (DRT). Therefore, gene sequencing, therapeutic drug monitoring and any possible measurement to predict DRT should be considered before determining the course of chemotherapy for XLA patients with CRC.
Case presentation
In this study, we reported a 21-year-old male who developed metastatic CRC in the context of XLA. Since the whole exome sequencing and therapeutic drug monitoring did not reveal any predictive markers of DRT, we applied standard first-line chemotherapy to the patient. However, progressive disease occurred after the fifth treatment cycle. Therefore, the administration of oxaliplatin was changed to irinotecan as second-line therapy. After that, the patient firstly suffered from severe hypocalcemia and eventually died due to metastatic CRC after the eighth treatment cycle. The overall survival time was 7.5 months.
Conclusions
This study reported the first written record of a Chinese XLA patient with metastatic CRC and severe hypocalcemia. Whole exome sequencing and bioinformatic analysis indicated the somatic mutations in ABCA6, C6 and PAX3 genes might contribute to the early-onset and metastasis CRC. Besides, a number of germline mutations in genes related to calcium metabolism (CACNA2D4, CD36, etc.) and the administration of irinotecan were speculated to be the causes of severe hypocalcemia. We therefore suggested that in order to avoid severe DRT, clinicians should take genetic background and therapeutic drug monitoring into consideration while planning chemotherapy treatment for XLA patients with CRC.
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