Acute emesis: moderately emetogenic chemotherapy

This paper is a review of the recommendations for the prophylaxis of acute emesis induced by moderately emetogenic chemotherapy as concluded at the third Perugia Consensus Conference, which took place in June 2009. The review will focus on new studies appearing since the Second consensus conference in April 2004. The following issues will be addressed: dose and schedule of antiemetics, different groups of antiemetics such as corticosteroids, serotonin(3) receptor antagonists, dopamine(2) receptor antagonists, and neurokinin(1) receptor antagonists. Furthermore, antiemetic prophylaxis in patients receiving multiple cycles of moderately emetogenic chemotherapy will be reviewed. Consensus statements are given, including optimal dose and schedule of serotonin(3) receptor antagonists, dexamethasone, and neurokinin(1) receptor antagonists. The most significant recommendations (and changes since the 2004 version of the guidelines) are as follows: the best prophylaxis in patients receiving moderately emetogenic chemotherapy (not including a combination of an anthracycline plus cyclophosphamide) is the combination of palonosetron and dexamethasone on the day of chemotherapy, followed by dexamethasone on days 2-3. In patients receiving a combination of an anthracycline plus cyclophosphamide, a combination of a serotonin(3) receptor antagonist plus dexamethasone, plus the neurokinin(1) receptor antagonist aprepitant on the day of chemotherapy, followed by aprepitant days 2-3, is recommended

Existence and multiplicity of positive periodic solutions for a class of higher-dimension functional differential equations with impulses

AbstractThis paper deals with the existence of multiple periodic solutions for n-dimensional functional differential equations with impulses. By employing the Krasnoselskii fixed point theorem, we obtain some easily verifiable sufficient criteria which extend previous results

Integrated safety analysis of rolapitant with coadministered drugs from phase II/III trials:an assessment of CYP2D6 or BCRP inhibition by rolapitant

Background: Rolapitant, a long-acting neurokinin (NK)1 receptor antagonist (RA), has demonstrated efficacy in prevention ofchemotherapy-induced nausea and vomiting in patients administered moderately or highly emetogenic chemotherapy. Unlikeother NK1 RAs, rolapitant does not inhibit or induce cytochrome P450 (CYP) 3A4, but it does inhibit CYP2D6 and breast cancerresistance protein (BCRP). To analyze potential drug-drug interactions between rolapitant and concomitant medications, thisintegrated safety analysis of four double-blind, randomized phase II or III studies of rolapitant examined adverse events (AEs) byuse versus non-use of drug substrates of CYP2D6 or BCRP. Patients and methods: Patients were randomized to receive either 180mg oral rolapitant or placebo ±1-2 h before chemotherapyin combination with a 5-hydroxytryptamine type 3 RA and dexamethasone. Data for treatment-emergent AEs (TEAEs)and treatment-emergent serious AEs (TESAEs) during cycle 1 were pooled across the four studies and summarized in the overallpopulation and by concomitant use/non-use of CYP2D6 or BCRP substrate drugs. Results: In the integrated safety population, 828 of 1294 patients (64%) in the rolapitant group and 840 of 1301 patients (65%)in the control group experienced at least one TEAE. Frequencies of common TEAEs were similar in the rolapitant and controlpopulations. Overall, 53% of patients received CYP2D6 substrate drugs, none of which had a narrow therapeutic index (likethioridazine or pimozide), and 63% received BCRP substrate drugs. When grouped by concomitant use versus non-use ofCYP2D6 or BCRP substrate drugs, TEAEs and TESAEs occurred with similar frequency in the rolapitant and control populations. Conclusions: The results of this study support the safety of rolapitant as part of an antiemetic triple-drug regimen in patientsreceiving emetogenic chemotherapy, including those administered concomitant medications that are substrates of CYP2D6 orBCRP, such as ondansetron, docetaxel, or irinotecan.</p

Delayed emesis: moderately emetogenic chemotherapy (single-day chemotherapy regimens only)

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Safety and antiemetic efficacy of weekly administration of netupitant/palonosetron plus dexamethasone during 5 weeks of concomitant chemo-radiotherapy—the DANGER-emesis study

Purpose: Netupitant 300 mg/palonosetron 0.5 mg (NEPA) would be ideal as antiemetic prophylaxis for patients receiving weekly cisplatin, as it would reduce concurrent medication intake compared to the 3-day aprepitant regimen. However, due to the longer half-life of netupitant (~ 88 h), weekly administration could potentially lead to accumulation and toxicity. This study aims to investigate the safety and antiemetic efficacy of weekly administration of NEPA plus dexamethasone (DEX) in patients treated for cervical cancer with radiotherapy and weekly cisplatin 40 mg/m2. Methods: This single-arm, open-label, phase II study evaluated patients with cervical cancer receiving NEPA and DEX before weekly cisplatin and concomitant radiotherapy for up to 5 weeks. Safety was assessed during weekly adverse event (AE) assessments. Efficacy was evaluated using Patient Diaries reporting daily nausea, vomiting, and use of rescue medication during the study period. Results: Between October 8, 2018, and January 2, 2024, 73 patients were recruited from two Danish departments of oncology; 37 completed all five weekly cycles. The majority of AEs were of mild or moderate intensity, with fatigue being the most frequently observed (95% of patients). Seven (10%) patients encountered ≥ 1 grade 3 treatment-related AEs (TRAEs). No grade 4 TRAEs or deaths were observed. In terms of efficacy, no vomiting and no nausea days 1–35 were 86% and 18%, respectively. Mean time to first emetic episode was 9 days. Conclusion: Weekly NEPA administration was safe, well-tolerated, and highly effective during concomitant radiotherapy and weekly cisplatin. Trial registration: This trial is registered at ClinicalTrials.gov (NCT03668639-2018–09-10).</p

Long-term safety in patients with recurrent ovarian cancer treated with niraparib versus placebo:Results from the phase III ENGOT-OV16/NOVA trial

Objective: Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor approved for use in heavily pretreated patients and as maintenance treatment in patients with newly-diagnosed or recurrent ovarian cancer following a response to platinum-based chemotherapy. We present long-term safety data for niraparib from the ENGOT-OV16/NOVA trial. Methods: This multicenter, double-blind, randomized, controlled phase III trial evaluated the efficacy and safety of niraparib for the treatment of recurrent ovarian cancer. Patients were randomly assigned 2:1 to receive either once-daily niraparib 300 mg or placebo. Two independent cohorts were enrolled based on germline BRCA mutation status. The primary endpoint was progression-free survival, reported previously. Long-term safety data were from the most recent data cutoff (September 2017). Results: Overall, 367 patients received niraparib 300 mg once daily. Dose reductions due to TEAEs were highest in month 1 (34%) and declined every month thereafter. Incidence of any-grade and grade ≥ 3 hematologic and symptomatic TEAEs was also highest in month 1 and subsequently declined. Incidence of grade ≥ 3 thrombocytopenia decreased from 28% (month 1) to 9% and 5% (months 2 and 3, respectively), with protocol-directed dose interruptions and/or reductions. Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) were reported in 2 and 6 niraparib-treated patients, respectively, and in 1 placebo patient each. Treatment discontinuations due to TEAEs were &lt;5% in each month and time interval measured. Conclusion: These data demonstrate the importance of appropriate dose reduction according to toxicity criteria and support the safe long-term use of niraparib for maintenance treatment in patients with recurrent ovarian cancer. Trial registration: ClinicalTrials.gov identifier: NCT01847274.</p