pyrimidinones and Nausea

pyrimidinones has been researched along with Nausea* in 9 studies

Reviews

1 review(s) available for pyrimidinones and Nausea

ArticleYear
Combination dabrafenib and trametinib in the management of advanced melanoma with BRAFV600 mutations.
    Expert opinion on pharmacotherapy, 2016, Volume: 17, Issue:7

    In the 40-50% of advanced melanoma patients with tumors harboring BRAF V600E and V600 K mutations, BRAF inhibitors such as dabrafenib are a highly effective treatment. However, most patients develop resistance after several months on treatment. The addition of a MEK inhibitor, such as trametinib, to BRAF inhibition mitigates one key pathway of resistance, further increasing response rates and improving survival.. This article summarizes the mechanism of action of the combination of dabrafenib and trametinib, its evolution through Phase I, II and III clinical trials and discusses its current use in the management of patients with advanced melanoma.. Combination therapy with dabrafenib and trametinib improves response rate, progression-free survival and overall survival when compared to dabrafenib or vemurafenib alone. The addition of trametinib to dabrafenib changes the adverse event profile, making hyperkeratosis and cutaneous squamous cell carcinomas less common but side effects such as fever and nausea more common. How dabrafenib/trametinib is best sequenced with other effective treatments such as immune checkpoint blockade remains uncertain.

    Topics: Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Fever; Humans; Imidazoles; MAP Kinase Signaling System; Melanoma; Mutation; Nausea; Oximes; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidinones; Skin Neoplasms

2016

Trials

6 trial(s) available for pyrimidinones and Nausea

ArticleYear
Targeting wild-type TP53 using AMG 232 in combination with MAPK inhibition in Metastatic Melanoma; a phase 1 study.
    Investigational new drugs, 2022, Volume: 40, Issue:5

    Targeting the MDM2-p53 interaction using AMG 232 is synergistic with MAPK inhibitors (MAPKi) in preclinical melanoma models. We postulated that AMG 232 plus MAPKi is safe and more effective than MAPKi alone in TP53-wild type, MAPKi-naïve metastatic melanoma.. Patients were treated with increasing (120 mg, 180 mg, 240 mg) oral doses of AMG 232 (seven-days-on, 15-days-off, 21-day cycle) plus dabrafenib (D) and trametinib (T) (Arm 1, BRAFV600-mutant) or T alone (Arm 2, BRAFV600-wild type). Patients were treated for seven days with AMG 232 alone before adding T±D. Safety and efficacy were assessed using CTCAE v4.0 and RECIST v1.1 criteria, respectively. Pharmacokinetic (PK) analysis was performed at baseline and steady-state levels for AMG 232.. 31 patients were enrolled. Ten and 21 patients were enrolled in Arm 1 and Arm 2, respectively. The most common AMG 232-related adverse events (AEs) were nausea (87%), diarrhea (77%), and fatigue (74%). Seven patients (23%) were withdrawn from the study due to AMG 232-related AEs. Three dose-limiting AEs occurred (Arm 1, 180 mg, nausea; Arm 2, 240 mg, grade 3 pulmonary embolism; Arm 2, 180 mg, grade 4 thrombocytopenia). AMG 232 PK exposures were not altered when AMG 232 was combined with T±D. Objective responses were seen in 8/10 (Arm 1) and 3/20 (Arm 2) evaluable patients. The median progression-free survival for Arm 1 and Arm 2 was 19.0 months-not reached and 2.8 months, respectively.. The maximum tolerated dose of AMG 232 for both arms was 120 mg. AMG 232 plus T±D exhibited a favorable PK profile. Although objective responses occurred in both arms, adding AMG 232 to T±D did not confer additional clinical benefit.

    Topics: Acetates; Antineoplastic Combined Chemotherapy Protocols; Humans; Melanoma; Nausea; Piperidones; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidinones; Tumor Suppressor Protein p53

2022
Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2018, 01-01, Volume: 36, Issue:1

    Purpose We report the efficacy and safety of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) combination therapy in BRAF V600E-mutated anaplastic thyroid cancer, a rare, aggressive, and highly lethal malignancy with poor patient outcomes and no systemic therapies with clinical benefit. Methods In this phase II, open-label trial, patients with predefined BRAF V600E-mutated malignancies received dabrafenib 150 mg twice daily and trametinib 2 mg once daily until unacceptable toxicity, disease progression, or death. The primary end point was investigator-assessed overall response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Results Sixteen patients with BRAF V600E-mutated anaplastic thyroid cancer were evaluable (median follow-up, 47 weeks; range, 4 to 120 weeks). All patients had received prior radiation treatment and/or surgery, and six had received prior systemic therapy. The confirmed overall response rate was 69% (11 of 16; 95% CI, 41% to 89%), with seven ongoing responses. Median duration of response, progression-free survival, and overall survival were not reached as a result of a lack of events, with 12-month estimates of 90%, 79%, and 80%, respectively. The safety population was composed of 100 patients who were enrolled with seven rare tumor histologies. Common adverse events were fatigue (38%), pyrexia (37%), and nausea (35%). No new safety signals were detected. Conclusion Dabrafenib plus trametinib is the first regimen demonstrated to have robust clinical activity in BRAF V600E-mutated anaplastic thyroid cancer and was well tolerated. These findings represent a meaningful therapeutic advance for this orphan disease.

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Fatigue; Female; Fever; Humans; Imidazoles; Male; Middle Aged; Mutation; Nausea; Neoplasm Metastasis; Oximes; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidinones; Thyroid Carcinoma, Anaplastic; Young Adult

2018
Similar safety and efficacy of once- and twice-daily lopinavir/ritonavir tablets in treatment-experienced HIV-1-infected subjects at 48 weeks.
    Journal of acquired immune deficiency syndromes (1999), 2010, Volume: 54, Issue:2

    To compare the safety and antiviral activity of once (QD) or twice (BID) daily lopinavir/ritonavir (LPV/r) in combination with investigator-selected nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in treatment-experienced subjects.. Subjects failing treatment with HIV-1 RNA > 1000 copies per milliliter received LPV/r tablets 800/200 mg QD (n = 300) or 400/100 mg BID (n = 299) with investigator-chosen nucleoside/nucleotide reverse transcriptase inhibitors. Efficacy was determined by the intent-to-treat time to loss of virologic response (ITT-TLOVR) algorithm. Safety, tolerability, adherence, impact of baseline protease mutations on virologic response, and emergence of resistance on therapy were assessed.. Demographics were comparable across groups. By intent-to-treat time to loss of virologic response, 166 QD subjects (55.3%) and 155 BID subjects (51.8%) were responders at week 48 (P = 0.413), with similar mean increases in CD4 T-cell count. QD subjects demonstrated better adherence than BID subjects. The occurrence of treatment-related moderate/severe adverse events was comparable for all events except nausea, which was reported more frequently among BID-treated subjects. Emergence of new protease resistance mutations on treatment was similarly infrequent in both groups.. LPV/r dosed QD resulted in increased treatment adherence and was as efficacious as BID LPV/r while providing similar safety, tolerability, and limited resistance evolution.

    Topics: Adult; Aged; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Drug Resistance, Viral; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Lopinavir; Male; Medication Adherence; Middle Aged; Nausea; Pyrimidinones; Ritonavir; Viral Load; Young Adult

2010
Effects of intermittent IL-2 alone or with peri-cycle antiretroviral therapy in early HIV infection: the STALWART study.
    PloS one, 2010, Feb-23, Volume: 5, Issue:2

    The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4(+) counts compared to no therapy.. Participants not on continuous ART with > or = 300 CD4(+) cells/mm(3) were randomized to: no treatment; IL-2 for 5 consecutive days every 8 weeks for 3 cycles; or the same IL-2 regimen with 10 days of ART administered around each IL-2 cycle. CD4(+) counts, HIV RNA, and HIV progression events were collected monthly.. A total of 267 participants were randomized. At week 32, the mean CD4(+) count was 134 cells greater in the IL-2 alone group (p<0.001), and 133 cells greater in the IL-2 plus ART group (p<0.001) compared to the no therapy group. Twelve participants in the IL-2 groups compared to 1 participant in the group assigned to no therapy experienced an opportunistic event or died (HR 5.84, CI: 0.59 to 43.57; p = 0.009).. IL-2 alone or with peri-cycle HAART increases CD4(+) counts but was associated with a greater number of opportunistic events or deaths compared to no therapy. These results call into question the immunoprotective significance of IL-2-induced CD4(+) cells.. ClinicalTrials.gov NCT00110812.

    Topics: Adult; Anti-HIV Agents; Atazanavir Sulfate; Carbamates; CD4 Lymphocyte Count; Drug Administration Schedule; Drug Therapy, Combination; Female; Fever; Furans; HIV Infections; Humans; Interleukin-2; Lopinavir; Male; Nausea; Oligopeptides; Opportunistic Infections; Organophosphates; Pyridines; Pyrimidinones; Ritonavir; Sulfonamides; Treatment Outcome

2010
A 96-week comparison of lopinavir-ritonavir combination therapy followed by lopinavir-ritonavir monotherapy versus efavirenz combination therapy.
    The Journal of infectious diseases, 2008, Jul-15, Volume: 198, Issue:2

    Antiretroviral-naive HIV-1-infected volunteers received zidovudine/lamivudine plus either lopinavir/ritonavir (n=104) or efavirenz (n=51). Lopinavir/ritonavir-treated subjects demonstrating 3 consecutive monthly HIV-1 RNA levels <50 copies/mL started lopinavir/ritonavir monotherapy. In previous-failure=failure analysis, 48% (lopinavir/ritonavir) and 61% (efavirenz) maintained HIV-1 RNA at <50 copies/mL through week 96, (P= .17; 95% confidence interval [CI] for the difference, -29% to 4%); in noncompletion=failure analysis, 60% (lopinavir/ritonavir) and 63% (efavirenz) maintained HIV-1 RNA at <50 copies/mL at week 96 (P= .73; 95% CI for the difference, -19% to 13%). Significant sparing of peripheral lipoatrophy was noted in the lopinavir/ritonavir simplification strategy. This study has provided important information for future studies using treatment simplified to lopinavir/ritonavir monotherapy.

    Topics: Acquired Immunodeficiency Syndrome; Alkynes; Anti-HIV Agents; Benzoxazines; Cyclopropanes; Diarrhea; Drug Therapy, Combination; Glucose Tolerance Test; HIV Protease Inhibitors; Humans; Lopinavir; Nausea; Pyrimidinones; Ritonavir; RNA, Viral; Time Factors; Treatment Outcome; Viral Load

2008
High incidence of adverse events in healthy volunteers receiving rifampicin and adjusted doses of lopinavir/ritonavir tablets.
    AIDS (London, England), 2008, May-11, Volume: 22, Issue:8

    Previous research in healthy volunteers has demonstrated that rifampicin and adjusted doses of lopinavir/ritonavir soft-gel capsules resulted in adequate exposure to lopinavir. Our objective was to study the combined use of rifampicin and the newly introduced lopinavir/ritonavir tablets.. A total of 40 healthy volunteers were planned to start with 600 mg rifampicin once daily from days 1-5. From days 6-15, volunteers were randomized to receive lopinavir/ritonavir tablets dosed as either 600/150 or 800/200 mg twice daily, both in addition to 600 mg rifampicin once daily. A 12 h pharmacokinetic curve was planned on day 15. Safety assessments were conducted regularly throughout the study period.. Eleven volunteers started as the first group in this study. No major complaints occurred during day 1-5 (rifampicin only). After addition of lopinavir/ritonavir, eight volunteers suffered from both nausea and vomiting, one from nausea only, and one from vomiting only. On day 7, increases in aspartate aminotransferase/alanine aminotransferase (AST/ALT) levels were reported in all volunteers and on day 8, the study was prematurely terminated. The AST/ALT levels continued to rise and peaked (grade 2, n = 2; grade 3, n = 1; grade 4, n = 8) on days 9-10. All values returned to normal within 6 weeks.. The study showed a high incidence of adverse events when a higher than standard dose of the new lopinavir/ritonavir tablets was combined with rifampicin. In the future, this drug combination should not be given to healthy volunteers. Liver function should be carefully monitored when rifampicin and lopinavir/ritonavir are combined in patients.

    Topics: Adult; Alanine Transaminase; Antibiotics, Antitubercular; Aspartate Aminotransferases; Drug Administration Schedule; Drug Combinations; Drug Interactions; Female; HIV Protease Inhibitors; Humans; Lopinavir; Male; Middle Aged; Nausea; Pyrimidinones; Rifampin; Ritonavir; Tablets; Vomiting

2008

Other Studies

2 other study(ies) available for pyrimidinones and Nausea

ArticleYear
[Substance P in antitumor drug-induced adverse reactions].
    Nihon yakurigaku zasshi. Folia pharmacologica Japonica, 2013, Volume: 142, Issue:5

    Topics: Animals; Antineoplastic Agents; Carboplatin; Histamine Antagonists; Humans; Nausea; Neuropeptides; Paclitaxel; Pyridines; Pyrimidinones; Substance P; Vomiting

2013
[Outpatient therapy of epilepsy].
    Zeitschrift fur arztliche Fortbildung, 1970, Jul-15, Volume: 64, Issue:14

    Topics: Anticonvulsants; Barbiturates; Depression, Chemical; Drug Eruptions; Drug Hypersensitivity; Epilepsies, Partial; Epilepsy; Epilepsy, Absence; Epilepsy, Temporal Lobe; Epilepsy, Tonic-Clonic; Ethosuximide; Humans; Leukopenia; Nausea; Outpatient Clinics, Hospital; Phenytoin; Pyrimidines; Pyrimidinones; Sleep; Vomiting

1970