Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tamoxifen has been found to be safe and effective in gynecological cancer patients with normal renal function. However, to our knowledge, no data exist regarding its effectiveness and toxicity in gynecological cancer patients with chronic kidney disease (CKD). Therefore, we retrospectively evaluated the effects of tamoxifen in patients with recurrent gynecological cancer and CKD. We collected clinical and demographic data for all patients. CKD was defined as a creatinine clearance (CrCl) level of less than 90 mL/min/1.73 m(2), in accordance with the National Kidney Foundation Kidney and Dialysis Outcomes Quality Initiative, and further categorized as mild, moderate, or severe (CrCl levels of 60-89, 30-59, and <30 mL/min/1.73 m(2), respectively). Twenty-nine patients were included in the study--22 with epithelial ovarian cancer, 4 with peritoneal cancer, and 3 with fallopian tube cancer. Thirteen patients had mild CKD, 13 had moderate, and 3 had severe. Most patients had been treated with 20 mg/day of tamoxifen every 4 weeks. The median duration of treatment was 5 months (range, 1-52 months). The overall complete response, partial response, stable disease, and disease progression rates were 0%, 10%, 41%, and 48%, respectively. Twenty-one percent of patients experienced hot flashes, and 7% experienced nausea. No major adverse reactions occurred. These findings were similar to those for gynecological cancer patients with normal renal function. In conclusion, 20 mg/day of tamoxifen is safe and effective in gynecological cancer patients with CKD.
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PMID:Tamoxifen is safe and effective in gynecological cancer patients with renal dysfunction. 1789 59

Sclerosing encapsulating peritonitis (SEP) is a rare cause of bowel obstruction. It is difficult to diagnose and the prognosis is poor. This report describes a case of SEP after living donor liver transplantation that was successfully treated with tamoxifen. A 56-year-old male, that had received a liver transplant for hepatitis C virus-related hepatocellular carcinoma 5 years earlier, was admitted with continuous abdominal pain and nausea. He had increased C-reactive protein levels and white blood cell count, and underwent laparotomy 5 days after hospitalization. The surgical findings showed ascites and SEP of the small bowel. An attempt to peel off the adhesions was stopped because there was a strong risk of intestinal tract damage. Tamoxifen treatment was initiated for SEP after surgery. The patient's symptoms gradually improved and he was able to resume feeding. He had been symptom-free for over 3 years at the last follow-up.
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PMID:Sclerosing encapsulating peritonitis after living donor liver transplantation: a case successfully treated with tamoxifen: report of a case. 2309 21

Tamoxifen, which is used to treat breast cancer, and ondansetron, used for the treatment of chemotherapy-induced nausea, are commonly metabolized via cytochrome P450 (CYP) 2D subfamily and 3A1/2 in rats, as in humans. This study was conducted to investigate the pharmacokinetic interactions between ondansetron and tamoxifen after intravenous and oral administration of ondansetron (both 8 mg/kg) and/or tamoxifen (2 and 10 mg/kg for intravenous and oral administration, respectively), in rats bearing 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammarian tumors (DMBA rats), used as an animal model of human breast cancer. The total area under the plasma concentration-time curve, from time zero to infinity (AUC) of tamoxifen was significantly greater after both intravenous and oral administration with ondansetron, compared to that after administration of tamoxifen-alone. The hepatic and intestinal metabolism of tamoxifen in DMBA rats was inhibited by ondansetron. Taken together, the significant increase in tamoxifen AUC in DMBA rats after intravenous or oral administration with ondansetron may be attributed to non-competitive hepatic (intravenous) and competitive intestinal (oral) inhibition of CYP2D subfamily- and 3A1/2-mediated tamoxifen metabolism by ondansetron.
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PMID:Pharmacokinetic drug interactions between ondansetron and tamoxifen in female Sprague-Dawley rats with DMBA-induced mammary tumor. 2339 44

Tamoxifen is an estrogen modulator that acts to competitively inhibit the binding of endogenous estrogens. It is widely used for treatment of breast cancer; however, analogous with many antineoplastic agents, tamoxifen is associated with numerous adverse effects, most prominently nausea. We have identified several off-target receptors of tamoxifen and 22 of its metabolites that include histamine H1 and H3, and muscarinic M1, M4, and M5 subtypes, and dopamine D2 receptor. We have shown how they are associated with tamoxifen and its metabolites' toxicity through a comprehensive computational analysis of their interaction modes, which were also compared to that of the related endogenous substrates of each receptor. The results were further evaluated using available in vivo and in vitro data. The presented work provides foundational knowledge toward the determination of the precise mechanism of nausea induction, and in particular, interactions of tamoxifen and its metabolites with the receptors involved in that biomolecular pathway. This study can assist in predicting the potential undesired effects of the chemicals with common pharmacophores or similar fragments to that of tamoxifen and its metabolites and serve drug discovery research in developing more effective and tolerable tamoxifen analogues or chemotherapeutic agents.
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PMID:Mechanism of Off-Target Interactions and Toxicity of Tamoxifen and Its Metabolites. 2856 38

Introduction: Hormonal therapy in endometrial cancer (EC) is used for patients who wish to preserve fertility and for patients with advanced or recurrent disease in a palliative setting. First line hormonal therapy consists of treatment with progestins, which has a response rate of 25% in an unselected population. Treatment with anti-estrogens is an alternative hormonal therapy option, but there is limited data on the effect and side-effects of anti-estrogens in EC. Therefore, we performed a systematic review to investigate the response rate and toxicity of anti-estrogenic therapy in patients with endometrial cancer. Methods: A systematic search in electronic databases was performed to identify studies on selective estrogen receptor modulators (SERM) and down-regulators (SERD) and aromatase inhibitors that reported on response rates (RR) among EC patients. Outcome in estrogen receptor (ER) positive and negative disease was assessed independently. Results: Sixteen studies on advanced stage and recurrent EC were included. Ten studies investigated anti-estrogen monotherapy and seven investigated a combination of anti-estrogenic drugs with either progestin or targeted treatment. Due to heterogeneity in patient population, no meta-analysis was performed. The median age of the patients in the included studies ranged from 61 to 71 years and the proportion of low grade tumors ranged from 38 to 80%. The RR for tamoxifen ranged from 10 to 53%, for other SERMs and SERDs 9-31%, for aromatase inhibitors from 8 to 9%, for combined tamoxifen/progestin treatment 19-58%, for combined chemo- and hormonal therapy 43% and for combination of anti-estrogenic treatment with mammalian target of rapamycin (mTOR) inhibitors 14-31%. Toxicity consisted mainly of nausea and thrombotic events and was higher in combination therapy of chemotherapy and hormonal therapy and hormonal therapy and mTOR inhibitors compared to other therapies. Conclusion: Tamoxifen or a combination of tamoxifen and progestin should be the preferred choice when selecting second line hormonal treatment because the RRs are similar to first line progestin treatment and the toxicity is low. The response can be optimized by selecting patients with endometrioid tumors and positive estrogen receptor status, which should be based on a pretreatment biopsy.
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PMID:Anti-estrogen Treatment in Endometrial Cancer: A Systematic Review. 3113 55

To systemically evaluate the clinical efficacy and safety of Hongjin Xiaojie Capsules for hyperplastic disease of breast(HDBA), so as to provide the evidence for its clinical application. The inclusion criteria are the RCT of single administration of Hongjin Xiaojie Capsules for treatment of HDBA. We retrieved following databases(CNKI, WanFang, VIP, SinoMed, Cochrane Library and PubMed) from their inception to October 1, 2019. Two researchers independently screened out literatures and extracted data, and assessed the methodological quality of eligible RCT according to the criteria in Cochrane Handbook for Systematic Reviews of Interventions. RevMan 5.3 was used for data analysis, binary data was summarized by risk ratio(RR) with confidence intervals(CI) of 95%, and continuous data were summarized by mean difference(MD) with CI of 95%. To estimate the sample size of systematic review, trial sequential analysis(TSA) was performed base on software TSA v0.9 version. Totally 14 RCTs were included, involving 3 057 patients. The results of Meta-analysis showed a significantly higher cure rate(RR=1.13, 95%CI[1.03, 1.25], P=0.01) and higher total effective rate(RR=1.09, 95%CI[1.05, 1.13], P&lt;0.000 1) in Hongjin Xiaojie Capsules group than those in the Juyuansuan Tamoxifen group. The incidence of adverse events was significantly higher in Juyuansuan Tamoxifen group than that in Hongjin Xiaojie Capsules group(RR=0.28 95%CI[0.16, 0.49], P&lt;0.001), and the adverse events included nausea, vomiting, abdominal pain, diarrhea, irregular menstruation, amenorrhea, unclear vision, dizziness and headache. The TSA for the cure rate demonstrated that the current available data reached the expected value. However, due to the low effect intensity of evidence, the pooled results might be affected by high risk bias of trials. The quality of evidence of included trials was generally low or very low. Inverted funnel diagram showed possible publication bias. This review suggested that Hongjin Xiaojie Capsules were potentially effective and safe in treatment of HDBA, especially, the incidences of drug-related adverse events from Hongjin Xiaojie Capsules were significantly lower than those from tamoxifen. However, because of lack of high-quality evidence for drawing a conclusion, more rigorously designed and high-quality trials are needed to confirm the efficacy and safety of Hongjin Xiaojie Capsules.
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PMID:[Systematic review and trial sequential analysis of randomized clinical trial of Hongjin Xiaojie Capsules for treatment of hyperplastic disease of breast]. 3316 45


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