Study Type – Prognosis (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Bone turnover markers such as BAP and 1CTP in patients with SRE or metastatic bone progression were significantly higher at a later phase after starting treatment with zoledronic acid compared with those without SRE or progression. However, there are no evident biomarkers predicting SRE or survival at an early phase after starting zoledronic acid treatment. The increase in serum 1CTP and BAP levels at an early phase after starting zoledronic acid treatment predicts short SRE‐free survival and overall survival. The measurement of bone turnover markers may be useful for physicians to inform patients of their prognosis and to determine the subsequent treatment plan. OBJECTIVE • To examine whether bone turnover markers could be predictive markers of the probability of newly arising skeletal‐related events (SRE) after the start of zoledronic acid treatment in patients with prostate cancer with bone metastasis. PATIENTS AND METHODS • In all, 30 patients with prostate cancer with bone metastasis were treated with zoledronic acid infusion every 4 weeks. • Serum C‐terminal crosslinking telopeptide of type 1 collagen (1CTP), bone alkaline phosphatase (BAP), and prostate‐specific antigen (PSA) levels were measured at the start of zoledronic acid treatment to establish baseline values, and every 4 weeks thereafter. • To judge in the early phase whether zoledronic acid is effective in these patients, we retrospectively compared 1CTP, BAP, and PSA levels at 1, 3, and 6 months after starting zoledronic acid treatment with those at baseline. RESULTS • SRE‐free survival of patients with increases of 1CTP levels at 1 and 3 months and BAP levels at 3 months were significantly poorer than those of patients with decreases in 1CTP or BAP levels (P = 0.001, P = 0.042, and P = 0.004, respectively). • Overall survival of patients with increases of 1CTP levels at 1 and 3 months and of BAP levels at 6 months were significantly poorer than those of patients with decreases of 1CTP or BAP levels (P = 0.013, P = 0.027, and P = 0.035, respectively). CONCLUSION • The measurement of 1CTP and BAP levels at an early phase after starting zoledronic acid treatment may be useful for physicians to inform patients of their prognosis and to determine the subsequent treatment plan.
Background Ritodrine hydrochloride (RD), a β2-adrenergic agonist, is widely used as a tocolytic medication to suppress premature labor, but can cause neonatal hypoglycemia, a potentially severe side effect. We examined the incidence and risk factors of neonatal hypoglycemia following maternal intravenous administration of RD. Methods This was a retrospective study of neonates, who had birth weight of ≥2000 g and were delivered at 36 weeks gestation or later in Kanazawa University Hospital from August 2013 to July 2016. We defined neonatal hypoglycemia as blood glucose level < 50 mg/dL. Neonates who were delivered without maternal intravenous RD or who were delivered 8 days or more after stopping maternal RD or who received oral RD were defined as the RD non-administration group, while those delivered within 7 days after stopping maternal RD were defined as the RD intravenous administration group. We examined the incidence and risk factors of RD-induced neonatal hypoglycemia by comparing these two groups. Results We enrolled 603 neonates in this study; 504 (83.6%) showed no neonatal hypoglycemia, while 99 (16.4%) exhibited neonatal hypoglycemia. The incidence of neonatal hypoglycemia was significantly higher (61.7%; 58/94) in the RD intravenous administration group than in the RD non-administration group (8.1%; 41/509) ( p < 0.001). Binomial logistic regression analysis in the RD intravenous administration group showed that maternal age over 35 years (AOR: 3.385; 95% CI, 1.082–10.588, p = 0.036) and the interval to delivery from stopping intravenous administration of RD (AOR: 0.974; 95% CI, 0.953–0.996, p = 0.020) were independent factors associated with neonatal hypoglycemia. The cut-off value of the interval to predict the incidence of neonatal hypoglycemia was about 6 h (sensitivity 82.8%, specificity 63.9%). Conclusions The incidence of neonatal hypoglycemia was significantly increased by maternal intravenous administration of RD. We newly identified maternal age (over 35 years) and the interval to delivery from stopping intravenous administration of RD (within 6 h) as independent risk factors for neonatal hypoglycemia following maternal intravenous administration of RD. In cases with these risk factors, careful blood glucose monitoring is recommended for early detection and treatment of neonatal hypoglycemia.
The relative stabilities of 1-aryl-1-(trifluoromethyl)ethyl cations were determined by measuring the proton-transfer equilibria of 1-aryl-1-(trifluoromethyl)ethylenes or the chloride-transfer equilibria of 1-aryl-1-(trifluoromethyl)ethyl chlorides in the gas phase. The stability of 1-phenyl-1-(trifluoromethyl)ethyl cation was found to be 16 kcal mol−1 lower than that of the α-cumyl (1-phenyl-1-methylethyl) cation. The substituent effect on the stability of this cation can be correlated in terms of the Yukawa–Tsuno equation, giving an r+ of 1.41 and a ρ of −10.0 (in log K/Ko−1 unit). While the ρ value is nearly identical to that of the α-cumyl cation series, the r+ value is remarkably higher than the value of unity for the α-cumyl cation, indicating that such a highly electron-deficient carbocation system should be characterized by an extremely large r+ value compared with that of the stable α-cumyl cation. In addition, this r+ value agrees with that for the SN1 solvolysis of 1-aryl-1-(trifluoromethyl)ethyl tosylates. Such agreement of the r+ values between the gas phase and solvolysis reactions has been generally observed for the benzylic carbocation systems. It is concluded that the enhanced r+ value for the solvolysis of 1-aryl-1-(trifluoromethyl)ethyl tosylates must reflect the intrinsic resonance demand characteristic of the parent 1-phenyl-1-(trifluoromethyl)ethyl cation, itself, and that the extremely large ρ+ values given by a simple correlation with σ+ (r+ = 1) are an artifact due to an improper analysis of underestimating the resonance demand for such highly deactivated substrates.
BackgroundBladder cancer patients receiving methotrexate, vinblastine, adriamycin and cisplatin (MVAC) chemotherapy are co-administered with dexamethasone as an anti-emetic. We examined whether or not dexamethasone affects the severity and onset day of MVAC-induced severe neutropenia.MethodsThis was a retrospective study of bladder cancer patients treated with MVAC chemotherapy with or without dexamethasone as an antiemetic at Kanazawa University Hospital during January 2005 - December 2009. Patients were categorized into three groups; no dexamethasone use (Dex (−)), dexamethasone on day 2 (Dex 1 day), and dexamethasone on days 2, 3 and 4 (Dex multiday). We evaluated the incidence of grade 3/4 neutropenia and the day of onset of first severe neutropenic episode during the first course of MVAC chemotherapy. Logistic regression was used to investigate whether co-administration of dexamethasone was a risk factor for severe neutropenia.ResultsEpisodes of grade 3/4 neutropenia occurred in 3 out of 6 (50.0%), 11 out of 12 (91.7%) and 6 out of 6 (100%) patients in the Dex (−), Dex 1 day, and Dex multiday groups, respectively. The appearance day of first severe neutropenia in the Dex multiday group (13.2 ± 1.0) was significantly accelerated compared to the Dex (−) group (17.7 ± 2.1). Univariate logistic regression analysis revealed that dexamethasone is a risk factor for severe neutropenia (OR 17.0; 95%CI: 1.3–223.1).ConclusionsCo-administration of dexamethasone for anti-emesis brings forward the first appearance of neutropenia, and increases the severity of neutropenia, in bladder cancer patients receiving MVAC chemotherapy.
Background: The tolerability of 2-weekly docetaxel at 25-35 mg/m 2 for castration-resistant prostate cancer (CRPC) has not been fully evaluated. The aim of this study was to evaluate its tolerability compared to 3-weekly docetaxel at 60-75 mg/m 2 in patients with CRPC. Patients and Methods: In this retrospective study, data were compared with respect to efficacy and safety between 2-weekly and 3-weekly docetaxel regimens in patients with CRPC. Results: Time to treatment failure and prostate-specific antigen (PSA) response rate did not differ significantly between the two regimens. Compared to 3-weekly administration, incidence of severe leukopenia and febrile neutropenia was significantly lower (p<0.05), and relative dose intensity was significantly higher (p<0.05) for the 2-weekly schedule. Docetaxel dosage and PSA response were identified as independent risk factors for severe leukopenia. Conclusion: Two-weekly treatment seems better tolerated than three-weekly treatment in Japanese patients with CRPC.Prostate cancer is estimated to account for 26% of new cancer cases worldwide (1), and the number of patients with prostate cancer is rapidly increasing in Japan (2). For advanced prostate cancer, hormone therapy or surgery are used as the initial treatment but most cases become resistant to treatment within 2-3 years and progress to castrationresistant prostate cancer (CRPC) (3).Since the effectiveness of 3-weekly docetaxel at 75 mg/m 2 with prednisone at 10 mg/day was reported in the TAX327 study in 2004 (4), docetaxel has been used for metastatic CRPC (mCRPC) as an international standard treatment. In Japan, a phase II study (ARD6562 study) was conducted to confirm the effectiveness of 3-weekly docetaxel at 70 mg/m 2 with prednisolone at 10 mg/day (5). Based on these results, 3-weekly docetaxel at 75 mg/m 2 was approved in Japan for CRPC in 2008, and docetaxel has been widely used in clinical practice for the treatment of CRPC. However, as the majority of patients with CRPC are elderly individuals and docetaxel resulted in grade 3-4 neutropenia for 93% of patients in a Japanese phase II trial (5), management of sideeffects associated with docetaxel is frequently difficult. Several 2-weekly regimens that reduced the individual dosages for docetaxel and shortened the interval between doses by 1 week have been devised. In an international phase III study, 2-weekly docetaxel at 50 mg/m 2 was better tolerated than 3-weekly docetaxel at 75 mg/m 2 (6). Based on these results, 2-weekly docetaxel at 50 mg/m 2 is listed in the National Comprehensive Cancer Network guidelines as an alternative for 3-weekly docetaxel at 75 mg/m 2 (7). On the other hand, in Japan changes in methods of docetaxel administration such as reduced dosage or extended dose interval have been suggested in order to reduce side-effects of docetaxel (8-11). However, the tolerability of 2-weekly docetaxel regimens has not yet been fully evaluated.The aim of this study was therefore to evaluate the tolerability of 2-weekly docetaxel at 25-35 mg/m 2 , t...
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