A new non-dilution rapid desensitization protocol successfully applied to all-grade platinum hypersensitivity.

PURPOSE: Desensitization is a safe alternative for patients with hypersensitivity reactions (HSRs) to platinum-based chemotherapeutic agents and widely used in real practice by employing stepwise administration of multiple serial dilutions of the culprit drugs. However, its labor-intensive nature has required a simpler protocol that is easier to prepare and perform. METHODS: We performed an observational study of patients with platinum HSR who underwent a new non-dilution one-bag desensitization protocol. Premedication consisted of Montelukast as well as H1 and H2 blockers. The outcomes and safety profiles of a new protocol were assessed. RESULTS: A total of 36 patients were recruited (oxaliplatin 23, carboplatin 9, and cisplatin 4) and the most common grade of HSR presented was grade 2 (61.1%), followed by grade 3 (25%), and grade 1 (13.9%). Of 175 desensitization procedures, all cases were successfully completed in re-administration of culprit chemotherapeutic platinum agents; 146 (83.4%) had no breakthrough reactions (BTRs) while 29 (16.6%) did. Most BTRs were mild reactions (grade 1, 51.7%) or moderate reactions (grade 2, 44.8%) of Brown's Scale. Although there was one case of asymptomatic mild hypotension (grade 3, 3.5%), categorized as severe reaction, dyspnea, desaturation, and anaphylaxis did not occur. The proportion of severe HSRs was significantly lower than that of initial HSRs (3.5% vs. 25%, P = 0.0167). CONCLUSIONS: The new non-dilution desensitization protocol was safe and effective for re-administration of culprit platinum agents in patients with a history of HSRs. Therefore, this new protocol can be used as an alternative to existing protocols using multiple serial dilutions.

Evaluation of the effects and adverse drug reactions of low-dose dexamethasone premedication with weekly docetaxel.

PURPOSE: A weekly docetaxel regimen had comparable efficacy with a tri-weekly schedule and caused significantly less severe neutropenia and febrile neutropenia. Therefore, a weekly docetaxel regimen has become increasingly common in cancer treatment. Premedication with corticosteroids can effectively prevent or reduce the severity of hypersensitivity and fluid retention. However, no recommended steroid dosage for a weekly docetaxel regimen has been established to date. The aim of this study is to compare the efficacy and complications of two different weekly docetaxel premedication protocols. METHODS: We retrospectively compared the hypersensitivity, hyperglycemia, and infection incidence associated with two weekly docetaxel premedication protocols. The control group (dexamethasone 10 mg intravenously and 4 mg orally every 12 h for four doses, starting 1 h before docetaxel administration) patients started weekly docetaxel chemotherapy between May 2012 and April 2013 at Seoul National University Hospital, and the experimental group (dexamethasone 10 mg intravenously 1 h prior to each docetaxel administration) patients started weekly docetaxel chemotherapy between May 2013 and April 2014. RESULTS: In total, 109 patients in the control group and 97 patients in the experimental group were included in this study, and there were no statistically significant differences in baseline characteristics between the two groups. The incidence of hypersensitivity and hyperglycemia were similar, but infections were observed significantly less in the experimental group (p = 0.020, OR = 0.408, 0.0190-0.0879). CONCLUSIONS: A low-dose dexamethasone premedication protocol has comparable efficacy in the prevention of docetaxel hypersensitivity with fewer infection complications. Therefore, we recommend a low-dose dexamethasone premedication protocol for weekly docetaxel regimens.

Awareness of the adverse effects associated with prophylactic corticosteroid use during docetaxel therapy.

PURPOSE: Weekly or tri-weekly docetaxel treatment mandates the use of dexamethasone to prevent toxicity. However, the adverse effects of prophylactic steroid use are often overlooked. We investigated the incidence of corticosteroid-associated adverse effects during docetaxel therapy, focusing on hyperglycemia and infection as well as the identification of possible risk factors. METHODS: This study was conducted through retrospective chart review of 632 patients who started docetaxel-based chemotherapy between July 2011 and June 2012 at Seoul National University Hospital. Hyperglycemia was defined as more than two random glucose levels >200 mg/dL. All documented episodes of infection that required treatment with antibiotics were regarded as infectious episodes. RESULTS: The incidences of hyperglycemia in overall patients and in patients without previous diabetes mellitus were 13.7 and 10.9%, respectively. Infectious episodes greater than grade 2 and grade 3 developed in 29.6 and 19.9% of patients, respectively. Multivariable logistic regression analysis showed that body mass index and previous diabetes mellitus were independent risk factors for hyperglycemia, whereas corticosteroid dose was not. Treatment duration and frequency of high blood glucose levels over 200 mg/dL were independent risk factors for infection. CONCLUSIONS: Due to the significant difference in patient and treatment characteristics, we could not obtain meaningful comparisons between weekly and tri-weekly docetaxel administration regimens. This study suggests that adverse effects associated with prophylactic steroid use need to be recognized and optimally managed during docetaxel therapy.

Impact of erythropoiesis-stimulating agents on red blood cell transfusion in Korea.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) have been shown to reduce the need for red blood cell (RBC) transfusions and to improve quality of life for cancer patients with anaemia. However, increased risks of mortality and disease progression have been reported when using ESAs with excessive target haemoglobin levels. In 2007, the United States Food and Drug Administration and Korea Food and Drug Administration issued regulatory alerts for using ESAs in cancer patients. OBJECTIVE: This retrospective study was performed to evaluate changes in ESA prescribing patterns between 2006 and 2010 and the impact on RBC transfusions in patients with solid tumours. SETTING: The Seoul National University Hospital (SNUH) in Korea. METHODS: This study includes adult patients with solid tumours who were diagnosed and treated in the SNUH from January 2006 to December 2010. The exclusion criterion was concomitant chronic renal failure. The patients' Hb levels and prescription data for ESAs and RBC transfusions were statistically analysed. The number of inpatient and outpatient solid-tumour patients was also analysed as a baseline. Main outcome measure Prescription data on ESAs and RBC transfusion. RESULTS: After adjusting for the number of patient visits, the monthly mean ESA doses dispensed decreased by an average of 1,192 mcg per quarter over the last 5 years, and the number of RBC transfusions ordered increased by 3.77 instances per quarter. After correcting for the number of patients, the mean doses of ESA dispensed each month decreased by 3,190 mcg per quarter, and the number of RBC transfusions ordered increased by 9.51 instances per quarter. CONCLUSION: During the last 5 years, the number of ESA doses dispensed at SNUH decreased and the number of RBC transfusions at SNUH increased, independent of the number of patients. The reduction in ESA use was thought to be due to the release of the safety alert letter in 2007. However, this study did not analyse other risk factors that may have influenced the number of RBC transfusions (e.g. metastatic cancer, comorbidities, surgery). Still, the results of this study suggest that the decreased ESA doses were relevant to the increased RBC transfusions.

Identifying drugs needing pharmacogenetic monitoring in a Korean hospital.

PURPOSE: A decision matrix for identifying drugs for which pharmacogenetic drug monitoring (PDM) provides the greatest benefit in a Korean setting is described. SUMMARY: We developed a decision matrix including the ethnic frequency of clinically relevant polymorphic cytochrome P-450 (CYP) enzymes, and the metabolic profiles and adverse drug reactions of drugs. Using the developed decision matrix based on the population allele frequencies of CYP enzymes, we identified potential candidates for PDM among the most commonly used drugs at Seoul National University Hospital (SNUH). Collectively, 17 of these drugs were largely metabolized by at least one polymorphic CYP enzyme. Pharmacogenetic information was used to identify CYP2C9, CYP2C19, and CYP2D6 as the major CYP enzymes of clinical importance for pharmacologic effect and safety in Koreans. The frequencies of poor and intermediate metabolizers among Koreans were 0% and 2.3-12% for CYP2C9, 12% and 42% for CYP2C19, and 0.44% and 28% for CYP2D6, respectively. The frequency of ultrarapid metabolizers of CYP2D6 was 2.28%. The decision matrix and pharmacogenetic information were used to identify seven drugs for PDM: warfarin, glimepiride, diazepam, amitriptyline, nortriptyline, codeine, and oxycodone. This approach can be applied to other institutional hospitals or other ethnic populations and would be helpful for advancing pharmacy practice. Further work is required to assess the practical and potential clinical relevance of pharmacogenetic variations on drugs of interest before the implementation of PDM. CONCLUSION: A decision matrix helped identify drugs for which PDM provides the greatest potential benefit at one Korean hospital.