Anti-emetic drugs in oncology: pharmacology and individualization by pharmacogenetics

Perwitasari, Dyah Aryani; Gelderblom, Hans; Atthobari, Jarir; Mustofa, Mustofa; Dwiprahasto, Iwan; Nortier, J.W.R.; Guchelaar, Henk‐Jan

doi:10.1007/s11096-010-9454-1

Cited by 57 publications

(46 citation statements)

References 54 publications

(88 reference statements)

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“…Belonging to the sensory circumventricular organs,4 the AP fulfills an exclusive function in chemotactic sensing between the central nervous system (CNS) and the blood stream with the blood–brain barrier (BBB) being replaced by specialized capillaries 4, 5 permeable to certain substances 6. The chemoreceptors of AP neurons are easily accessible for endo‐ and exogenous substances and multiple neurotransmitters are involved in the emetic reflex 7. However, some trigger pathologies of AP syndrome are under‐recognized since the exact pathophysiologic mechanisms are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Area postrema syndrome as frequent feature of Bickerstaff brainstem encephalitis

Zeiner

Brandhofe

Müller–Eschner

et al. 2018

Ann Clin Transl Neurol

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ObjectiveArea postrema (AP) syndrome (defined as: nausea and/or emesis and/or singultus at onset of brainstem dysfunction) comprises complex pathophysiologic mechanisms triggered by different entities. The first objective was to assess the frequency of AP syndrome as a clinical feature in brainstem encephalitis (BE). Finding an especially high prevalence of AP syndrome in Bickerstaff brainstem encephalitis (BBE), we also analyzed the frequency of AP syndrome in other autoimmune diseases with anti‐ganglioside antibodies (Guillain–Barré syndrome (GBS) and its variants).MethodsWe systematically evaluated the prevalence of AP syndrome in BE in all patients treated at our university hospital during a 15‐year period. In a second step, BBE patients were compared to GBS and Miller Fisher syndrome (MFS) patients as clinical subtypes of a disease continuum without brainstem dysfunction.ResultsWe found AP syndrome in 8 of 21 BE patients, including 3 of 7 BBE and in 4 of 112 GBS/MFS patients. AP syndrome was as a frequent but under‐recognized feature of BE with a significant impact on patients’ well being.InterpretationManifestation of AP syndrome in BBE but also in GBS and its subtypes point toward a role of autoimmune antibodies that should be investigated in future studies. Considerable misdiagnosis or nonrecognition complicates diagnostic and therapeutic management. Therefore, AP syndrome should be considered in any episode of otherwise unexplained nausea, emesis, or singultus.

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Section: Introductionmentioning

confidence: 99%

Area postrema syndrome as frequent feature of Bickerstaff brainstem encephalitis

Zeiner

Brandhofe

Müller–Eschner

et al. 2018

Ann Clin Transl Neurol

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“…Chemotherapy is thought to induce nausea and vomiting by triggering the release of neurotransmitters from cells lining the gastrointestinal (GI) tract. These neurotransmitters initiate a feedback loop between the GI tract and several regions of the brain, the result of which is an emetic response (4,5). Chemotherapy-induced nausea and vomiting (CINV) is treated with antiemetic drugs that target the serotonin (5-hydroxytryptamine-3; 5-HT3), substance P (SP), dopamine (DA), histamine (HA), and prostaglandin signaling pathways (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Patterns of antiemetic prophylaxis for chemotherapy-induced nausea and vomiting in China

Zong¹,

Zhang²,

Ji³

et al. 2016

Chinese Journal of Cancer Research

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Background: Few studies have attempted to evaluate the use of antiemetic therapy for chemotherapyinduced nausea and vomiting (CINV) at a national level in China or to assess how treatment regimens adhere to current guidelines. Methods:We searched the China Health Insurance Research Association (CHIRA) Database to identify patients with cancer who were ≥18 years old and received either moderately or highly emetogenic chemotherapy (MEC and HEC, respectively) between 2008 and 2012. Patients' characteristics as well as usage of specific antiemetic regimens were analyzed using descriptive statistics.Results: Of the 14,548 patients included in the study, 6,477 received HEC while 8,071 were treated with MEC. Approximately 89.9% used antiemetics prophylactically to prevent acute CINV and 71.5% for delayed CINV while 9.0% were prescribed antiemetics as rescue therapy. A significantly lower proportion of patients treated with HEC received prophylactic antiemetic therapy for delayed CINV as compared to those treated with MEC (59.4% vs. 81.3%; P<0.001). The HEC group had a slightly lower proportion of patients using a mixed regimen containing a 5-HT3 antagonist to prevent both acute and delayed CINV than the MEC group (P≤0.012); however, a higher proportion received a mixed regimen containing corticosteroids (P≤0.007). Although more than half of the patients in the HEC group took three antiemetics to prevent acute and delayed CINV, these rates were significantly lower than those of the MEC group (both P<0.001).Finally, analysis of the regimens used revealed that there is over-utilization of drugs within the same class of antiemetic.Conclusions: These findings indicate that more attention is needed for treatment of delayed CINV, in terms of both overall use and the components of a typical treatment regimen.

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“…Even some previous studies did not show the consistency about the significancy of statistical results, however the pattern of the genotypes and the patients' response were similar. [6][7][8][9][10] One of the previous study supported that the polimorphism of CYP2D6 resulted the significant difference of tropisetron serum concentration in poor metabolizer, extensive metabolizer and ultra-rapid metabolizer. 8 This study is aimed to evaluate the association between ondansetron serum concentration and the antiemetic responses, polymorphisms of 5HT3B receptor, CYP2D6 and ABCB1 genes in Indonesian cancer patients treated with high emetogenic cytostatics.…”

Section: Introductionmentioning

confidence: 82%

Ondansetron serum concentration and polymorphisms of CYP2D6, ABCB1 and 5-HT3B receptor genes in the treatment of chemoterapy induced nausea and vomiting

Perwitasari

Mustofa

2016

JMedScie

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This study was aimed to understand differences of ondansetron serum concentration in each antiemetic responses, polymorphisms of 5HT3B receptor, CYP2D6 and ABCB1 genes in Indonesian cancer patients treated with high emetogenic cytostatics. We recruited cancer patients in Dr Sardjito Hospital treated with cisplatin (≥ 50 mg/m 2 ) as monotherapy or combination therapy. Patients were treated with ondansetron 8 mg intravenously and dexamethasone 8 mg intravenously and metoclopramide (10 mg orally) after cytostatic administration until 5 days after chemotherapy. We cathegorized the nausea and vomiting grade according to the National Cancer Institute Common Toxicity Criteria v.3. We also determined some SNPs of ABCB1, 5HT3B and CYP2D6 genes using realtime PCR. We recruited 191 cancer patients in this study with the average of ondansetron serum concentration reached 33.48 ng/ml (SD: 18.54). According to the patients' response to the antiemetic, during the acute phase, 21.8% patients experienced acute nausea and 30.2% patients experienced acute vomiting. Only the haplotype of CTG-CTG of ABCB1 which have significant association with ondansetron serum concentration. EM patients of CYP2D6 and patients with haplotype of delAG of 5HT3B had lower ondansetron serum concentration. However, IM patients of CYP2D6 showed higher ondansetron serum concentration and lower grade of nausea and vomiting. Variations of ABCB1, CYP2D6 and 5HT3B may be used as pharmacogenetic marker in predicting antiemetic response in cancer patients receiving highly emetogenic cytostatic. ABSTRAKPenelitian ini bertujuan untuk mengetahui perbedaan konsentrasi ondansetron serum dalam setiap respon antiemetik, polimorfisme gen reseptor 5HT3B , CYP2D6 dan ABCB1 pada pasien kanker yang mendapatkan sitostatika emetogenik tinggi di Indonesia. Subjek dalam penelitian ini adalah pasien kanker di RSUP Dr Sarjito Hospital yang mendapatkan terapi sisplatin (≥ 50 mg/m 2 ) baik sebagai terapi tunggal maupun kombinasi. Subjek mendapatkan terapi ondansetron 8 mg, iv dan deksametason 8 mg, dan metoklopramid setelah pemberian sitostatika sampai hari kelima kemoterapi. Kategori mual muntah berdasarkan National Cancer Institute Common Toxicity Criteria v.3. Beberapa SNPs pada

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Anti-emetic drugs in oncology: pharmacology and individualization by pharmacogenetics

Cited by 57 publications

References 54 publications

Area postrema syndrome as frequent feature of Bickerstaff brainstem encephalitis

Area postrema syndrome as frequent feature of Bickerstaff brainstem encephalitis

Patterns of antiemetic prophylaxis for chemotherapy-induced nausea and vomiting in China

Ondansetron serum concentration and polymorphisms of CYP2D6, ABCB1 and 5-HT3B receptor genes in the treatment of chemoterapy induced nausea and vomiting

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