scholarly journals A Randomized, Double-Blind Pilot Study of Dose Comparison of Ramosetron to Prevent Chemotherapy-Induced Nausea and Vomiting

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Ka-Rham Kim ◽  
Gaeun Kang ◽  
Myung-Seo Ki ◽  
Hyun-Jeong Shim ◽  
Jun-Eul Hwang ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Optimal Dose ◽  
Complete Response ◽  
Dose Titration ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Double Blind ◽  
Dose Comparison ◽  
Subsequent Cycle ◽  
Delayed Cinv ◽  
Acute Cinv

Purpose. This study was conducted to determine the optimal dose titration of ramosetron to prevent the Rhodes Index of Nausea, Vomiting, and Retching (RINVR).Methods. Patients treated with folic acid, 5-fluorouracil, and oxaliplatin were randomized into three groups (0.3 mg, 0.45 mg, and 0.6 mg ramosetron before chemotherapy). The pharmacokinetics and pharmacodynamics using RINVR were evaluated.Results. Seventeen, 15, and 18 patients received ramosetron at doses of 0.3 mg, 0.45 mg, and 0.6 mg, respectively.Tmax(h),Cmax(ng/mL), andAUClast(ng·h/mL) were associated with dose escalation significantly, showing a reverse correlation with the RINVR during chemotherapy. Acute CINV was observed in four patients (22.2%), two patients (14.3%), and one (5.6%) patient and a delayed CINV on day 7 was found in eight (47%), three (21.4%), and five (27.8%) patients in each group. The complete response rate was increased with dose escalation (35.3%, 50.0%, and 72.2% in each group) and also showed the tendency for decreasing moderate-to-severe CINV.Conclusions. This study shows a trend regarding the dose-response relationship for ramosetron to prevent CINV, including delayed emesis. It suggested that dose escalation should be considered in patients with CINV in a subsequent cycle of chemotherapy, and an individual approach using RINVR could be useful to monitor CINV.

NEPA as antiemetic prophylaxis after failure of 5HT3-RA plus dexamethasone in patients receiving carboplatin and gemcitabine chemotherapy: A monocentric real-life experience

2020 ◽  
pp. 107815522092940
Author(s):  
Maria Rosaria Valerio ◽  
Vittorio Gebbia ◽  
Nicolò Borsellino ◽  
Maria La Vecchia ◽  
Vincenzo Serretta ◽  
...  
Keyword(s):  
Combination Chemotherapy ◽  
Rescue Medication ◽  
Life Experience ◽  
Real Life ◽  
Complete Response ◽  
Antiemetic Prophylaxis ◽  
Phase 0 ◽  
Subsequent Cycle ◽  
Delayed Cinv

Introduction Chemotherapy-induced nausea and vomiting (CINV) may affect adherence to planned chemotherapy treatments and compromise patients’ quality of life during the therapy. NEPA is an oral fixed combination of netupitant, a highly-selective NK1-RA and palonosetron, a 5HT3-RA, approved for the prevention of acute and delayed CINV. The aim of this study was to evaluate the efficacy and safety of NEPA with dexamethasone for CINV prophylaxis in the challenging setting of carboplatin and gemcitabine combination chemotherapy, after failure of prophylaxis with 5HT3 receptor antagonist. Methods Eligible patients were undergoing carboplatin and gemcitabine combination chemotherapy for metastatic non-small cell lung cancer (NSCLC), ovarian cancer or urothelial cancer and experienced nausea and/or vomiting after the first cycle of chemotherapy, despite an antiemetic prophylaxis with a 5HT3-RA and dexamethasone. Primary efficacy endpoint was complete response (CR: no emesis, no rescue medication) obtained with NEPA, during the overall phase (0–120 h), after the start of chemotherapy. Results During the first cycle of chemotherapy, 15 out of 30 (50%) patients did not properly control CINV with a 5HT3-RA plus dexamethasone used as primary antiemetic prophylaxis and then were switched to NEPA from the subsequent cycle. During NEPA administration, 13 out of 15 patients (86.7%) achieved an overall CR (no emesis, no rescue medication). Antiemetic treatment with NEPA was very well tolerated with only two patients (13.3%) that experienced a grade 1 TEAE. Conclusions Our experience showed that NEPA has proven to be very effective and well tolerated in the prophylaxis of CINV induced by carboplatin-based chemotherapy.

scholarly journals Effects of Diazoxide-Mediated Insulin Suppression on Glucose and Lipid Metabolism in Nondiabetic Obese Men

2018 ◽  
Vol 103 (6) ◽  
pp. 2346-2353 ◽  
Author(s):  
Sandra Loves ◽  
Lenneke van Groningen ◽  
Margreet Filius ◽  
Marja Mekking ◽  
Tom Brandon ◽  
...  
Keyword(s):  
Side Effects ◽  
Plasma Lipid ◽  
Exercise Program ◽  
Optimal Dose ◽  
Dose Titration ◽  
Double Blind ◽  
Insulin Levels ◽  
Glucose And Lipid Metabolism ◽  
The Mean ◽  
The Cost

Abstract Context It has been suggested that stimulation of lipolysis by diazoxide (DZX)-mediated insulin suppression may be useful in treating obesity. However, the optimal dose to promote lipolysis without causing hyperglycemia is unknown. Objective To assess the effects of DZX in nondiabetic obese men on lipid and glucose metabolism. Design Double-blind, placebo (PL)-controlled, 6-month trial in men with a body mass index of 30 to 37.5 kg/m2 treated with a combination of caloric restriction, a standardized exercise program, and DZX or PL dose escalation. Results The mean maximal tolerated dose of DZX was 422 ± 44 mg/d (range, 200 to 700 mg/d). Dose-limiting events were edema (n = 11), hyperglycemia (n = 6), and nausea (n = 2). After dose reduction to a level free of clinical side effects, DZX treatment was associated with a markedly greater decrease in fasting insulin levels than PL (−72.3 ± 3.5% vs −23.0 ± 12.6%; P < 0.001) and a significant improvement of blood pressure and plasma lipid levels. The decline in insulin levels occurred at the cost of a small increase in plasma glucose (0.6 ± 0.2 mmol/L vs −0.1 ± 0.1 mmol/L; P = 0.04) and hemoglobin A1C (0.2 ± 0.1% vs 0.0 ± 0.1%; P = 0.17). Conclusion In nondiabetic obese men, insulin levels can be reduced up to 70% without major metabolic side effects. The marked intersubject variation in maximal tolerated dose indicates that DZX dose titration needs to be individualized.

Phase III study of palonosetron (PALO) given as 30-min IV infusion (IV inf) versus 30-sec IV bolus (IV bol) for prevention of chemotherapy-induced nausea and vomiting (CINV) associated with highly emetogenic chemotherapy (HEC).

2017 ◽  
Vol 35 (31_suppl) ◽  
pp. 227-227 ◽  
Author(s):  
Meinolf Karthaus ◽  
Péter Szabò ◽  
Daniel Voisin ◽  
Giada Rizzi ◽  
Tudor Ciuleanu
Keyword(s):  
Study Drug ◽  
Complete Response ◽  
Risk Difference ◽  
Primary Objective ◽  
Phase Iii ◽  
Cardiac Symptoms ◽  
Phase Iii Study ◽  
Secondary Objective ◽  
Delayed Cinv ◽  
Acute Cinv

227 Background: PALO (0.50 mg), a distinctive second-generation 5-HT3 receptor antagonist (RA), is a component of the oral fixed combination agent NEPA, the second component being the NK1 RA netupitant. Oral NEPA is approved for acute and delayed CINV prophylaxis after moderately (MEC) and HEC. This study was conducted in support of the NEPA IV formulation (0.25 mg PALO + 235 mg fosnetupitant) administered as a 30-min IV inf, currently under FDA review. Methods: Chemotherapy-naive patients (pts) with solid tumors were randomized (1:1) to receive a single 0.25-mg PALO as a 30-min IV inf or a 30-sec IV bol, 30 min before reference HEC (cisplatin; dacarbazine), with oral dexamethasone (20 mg [D1]; 8 mg BID [D2–4]) (NCT02557035). Primary objective: noninferiority (NI; lower limit of the 99% CI to be > –15% [prespecified NI margin]) in complete response (CR; no emesis/no rescue) in the acute (0–24 h) phase. Secondary objective: safety. Results: 440 pts (median age 59.4 y [25–79]; cisplatin: 97.3%; dacarbazine: 2.7%) were randomized to IV inf (n=225) or IV bol (n=215). Baseline characteristics were similar. Acute CR rate was 82.7% (IV inf) and 86.5% (IV bol), with risk difference of –3.8% (99% CI: –12.2; 4.7) meeting the primary objective of NI. Treatment-emergent AE and study drug-related AE frequency was similar in both arms (Table). One PALO IV inf patient with pre-existing cardiac symptoms, experienced 1 serious AE that eventually lead to death and was considered possibly study drug-related by the investigator. No G≥3 infusion site reactions occurred. No patient in IV inf arm had infusion interruptions. Conclusions: PALO IV inf was noninferior to IV bol in acute CINV prevention after receiving non-AC HEC. Safety profiles were similar. No specific infusion toxicities were observed. The results show that PALO 0.25 mg IV inf is appropriate for the NEPA IV formulation. Clinical trial information: NCT02557035. [Table: see text]

scholarly journals 0752 JZP-258 Dose Titration and Transition from Sodium Oxybate in a Placebo-Controlled, Double-Blind, Randomized Withdrawal Study in Adult Participants With Narcolepsy With Cataplexy

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A286-A286
Author(s):  
N Foldvary-Schaefer ◽  
R K Bogan ◽  
M J Thorpy ◽  
L Huang ◽  
R Skowronski ◽  
...  
Keyword(s):  
Standard Of Care ◽  
Optimal Dose ◽  
Sodium Oxybate ◽  
Study Entry ◽  
Dose Titration ◽  
Open Label ◽  
Double Blind ◽  
Stable Dose ◽  
Dose Period ◽  
Treatment Naïve

Abstract Introduction Sodium oxybate (SXB) is a standard of care for the treatment of cataplexy and excessive daytime sleepiness in narcolepsy. JZP-258 is an oxybate product candidate (at same concentration as SXB) with 92% less sodium. JZP-258 dose adjustment during titration was evaluated. Methods At study entry, participants were taking SXB only, SXB+other anticataplectics, anticataplectics other than SXB, or were cataplexy treatment-naive. JZP-258 treatment began during a 12-week, open-label optimized treatment and titration period. Participants taking SXB only or SXB+other anticataplectics transitioned to JZP-258 at the same gram-for-gram dose as SXB and titrated to an efficacious and tolerable (optimal) dose from weeks 3-12. Participants taking other anticataplectics or who were anticataplectic-naive initiated JZP-258 at 4.5 g/night and were titrated to an optimal dose at 1-1.5 g/night/week (maximum total dose, 9 g/night). A 2-week stable-dose period and 2-week, double-blind, randomized withdrawal period followed. Results During the stable-dose period, total nightly JZP-258 dose (median [range]) was higher in participants taking SXB at study entry (SXB-only, 7.5 g [4.5-9.0], n=45; SXB+other anticataplectics, 9.0 g [6.0-9.0], n=14) compared with those not taking SXB (other anticataplectics, 7.5 g [4.5-9.0], n=23; anticataplectic-naive, 7.0 g [3.0-9.0], n=67), and dose adjustments were fewer. In most (69%) participants taking SXB at study entry who entered the stable-dose period, no change in dose was required (median [range] number of adjustments was 0 ([0-8]); for those with a change in dose, most changes were within one titration step (1.5 g/night). In participants not taking SXB at study entry, the median (range) number of adjustments was 3.0 (0-7). Conclusion Most participants taking SXB at study entry transitioned to JZP-258 treatment at the same dose with retained effectiveness. Participants not previously taking SXB achieved a tolerable and efficacious dose of JZP-258 after a median of 3 adjustments. Support Jazz Pharmaceuticals

A phase II trial of olanzapine and palonosetron for the prevention of chemotherapy induced nausea and vomiting (CINV)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8608-8608 ◽  
Author(s):  
R. M. Navari ◽  
L. H. Einhorn ◽  
P. J. Loehrer ◽  
S. D. Passik ◽  
J. Vinson ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Complete Response ◽  
Emetogenic Chemotherapy ◽  
Moderately Emetogenic Chemotherapy ◽  
Acute Period ◽  
Oral Olanzapine ◽  
Delayed Cinv ◽  
Acute Cinv ◽  
Ecog Ps

8608 Background: Olanzapine has been shown to be a safe and effective agent for the prevention of CINV in chemotherapy naïve cancer patients. Palonosetron has been approved for the prevention of acute CINV and for the prevention of delayed CINV in patients receiving moderately emetogenic chemotherapy (MEC). Methods: A phase II trial was performed for the prevention of CINV in chemotherapy naïve patients using the combination of olanzapine and palonosetron. The regimen was 10 mg of oral olanzapine, 0.25 mg of intravenous palonosetron, and dexamethasone (20 mg for highly emetogenic and 8 mg for moderately emetogenic chemotherapy) on the day of chemotherapy, day 1, and 10 mg/day of oral olanzapine alone on days 2–4 after chemotherapy. Forty patients (median age 60 yrs, range 38–84; 22 females; ECOG PS 0,1) consented to the protocol and all were evaluable. Results: The percentage of patients with a complete response (CR) (no emesis, no rescue) was 100% for the acute period (24 h post chemotherapy), 75% for the delayed period (days 2–5 post chemotherapy), and 75% for the overall period (0–120 h) for eight patients receiving highly emetogenic chemotherapy (HEC) (cisplatin > 70 mg/m2). CR was 97% for the acute period, 75% for the delayed period, and 72% for the overall period in 32 patients receiving MEC (doxorubicin, >50mg/m2). In the patients receiving HEC, the percentage of patients without nausea (0, scale 0–10, M. D. Anderson Symptom Inventory) was 100% in the acute period, 50% in the delayed period, and 50% in the overall period. In patients receiving MEC, the percentage without nausea was 100% in the acute period, 78% in the delayed period, and 78% in the overall period. There were no Grade 3 or 4 toxicities and no significant pain, fatigue, disturbed sleep, memory changes, dyspnea, lack of appetite, drowsiness, dry mouth, mood changes or restlessness experienced by the patients. CR and control of nausea in subsequent cycles of chemotherapy (35 patients, cycle 2; 31 patients cycle 3; 23 patients, cycle 4) were equal to or greater than cycle one. Conclusions: The combination of olanzapine and palonosetron with dexamethasone given only on the day of chemotherapy was safe and highly effective in controlling acute and delayed CINV in patients receiving HEC and MEC. No significant financial relationships to disclose.

scholarly journals Efficacy of Granisetron in the Prevention of Nausea and Vomiting among Paediatric Oncology Patients Receiving Moderate to Highly Emetogenic Chemotherapy: A Single-Blinded, Non-Inferiority Trial

2021 ◽  
Vol 50 (6) ◽  
pp. 1707-1714
Author(s):  
Sie Chong Doris Lau ◽  
Khai Soh Cheng ◽  
C-Khai Loh ◽  
Syed Zulkifli Syed Zakaria ◽  
Hamidah Alias
Keyword(s):  
Bone Tumour ◽  
Complete Response ◽  
Paediatric Oncology ◽  
Emetogenic Chemotherapy ◽  
Nausea And Vomiting ◽  
Highly Emetogenic Chemotherapy ◽  
Study Population ◽  
Delayed Cinv ◽  
Acute Cinv ◽  
To Receive

This single-blinded, non-inferiority trial was conducted over an 8-month period to examine the efficacy of intravenous granisetron at two differing doses in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV)among paediatric patients receiving moderate to highly emetogenic chemotherapy. Seventeen patients (9 males and 8 females) were recruited and randomly assigned to receive alternating granisetron dosages of 0.01 mg/kg and 0.04 mg/kg during each chemotherapy cycle. The severity of CINV during and three days post-completion of chemotherapy, as well as common side effects of granisetron were recorded. A total of 78 cycles of chemotherapy (38 cycles of 0.01 mg/kg and 40 cycles of 0.04 mg/kg) were evaluated. The median age of the study population was 5.2 years (interquartile range 25th, 3.8; 75th, 8.7). Patients’ diagnoses comprised of haematological malignancy, bone tumour and cerebral neoplasm. From this study, we demonstrated that intravenous (IV) granisetron 0.01 mg/kg was non-inferior to 0.04 mg/kg in terms of achieving a complete response for acute CINV. However, a similar observation was not seen in the post-treatment period analysis (delayed CINV). In conclusion, IV granisetron at 0.04 mg/kg/dose provides effective protection and prophylaxis of both acute and delayed CINV. Further study with a larger sample size may be required before a definite conclusion can be made with regards to efficacy of 0.01 mg/kg dose.

An Interim Analysis of Phase II, Open Randomized Comparative Trial: Alternate or Multiple-Day Dosing of Palonosetron (PALO) Is Effective and Safe in the Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) in Patients (pts) with Leukemia Receiving High Dose Ara-C (HDAC).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2840-2840 ◽  
Author(s):  
Gloria Mattiuzzi ◽  
Jorge Cortes ◽  
Jennifer Cassat ◽  
Deborah Blamble ◽  
B. Nebiyou Bekele ◽  
...  
Keyword(s):  
Performance Status ◽  
Comparative Trial ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Complete Control ◽  
Delayed Cinv ◽  
Grade 3 ◽  
Moderate Nausea ◽  
Acute Cinv

Abstract Background: CINV is a significant problem for pts with leukemia undergoing multiple-day, high-dose chemotherapy (MD-HD-CHEMO). (PALO) has higher binding affinity to 5-HT3 receptors, higher potency and longer half-life than first generation 5-HT3 receptor antagonists, which, in addition, are not effective in preventing delayed CINV. Study Objectives: To compare if PALO given in alternate doses or in multiple-day dosing is better than ondansetron (ONDA) given daily in the prevention of CINV in pts with AML/HR-MDS receiving MD-HD-CHEMO with HDAC containing regimens (AraC =1.5 or 2gm/m2 for 3–5 days). Methods: Eligible pts were randomized to receive 30 minutes before CHEMO: ONDA: 8 mg IV bolus, then 24mg IV, continuous infusion on d1 through d5 and for 12 hours after Ara C infusion ends [ONDA 1–5]; or PALO 0.25mg IV bolus over 30 seconds, on d1 through d5 of Ara C infusion, [PALO 1–5]; or PALO 0.25mg IV bolus over 30 seconds, on day 1,3, and 5 of Ara C infusion (PALO 1,3,5). All patients received Solumedrol 40 mg IV before AraC. Complete response (CR) was defined as no emesis and no use of rescue medication (RM) during the administration of chemo and up to 7 days; Complete control (CC) was define as CR + pts with ≤ 1 episode of emesis within 24 hours and no more than moderate nausea with no need of RM for either case. Failure (F) was defined as the needs to use of RM. Pts were followed for 7 days. A diary to evaluate impact of CINV on daily activities was filled by the pts during the 7 days. Hereby we present data in the first 95 evaluable patients. The 3 group of pts were comparable in regards to age, gender, race, performance status, history of alcohol use and smoking habits. Response rates are shown in the table below. Although not statistically significant (p= 0.178), less pts in either PALO arm had CINV on day 1 (28%, 10% and 22 for ONDA 1–5, PALO 1–5 and Palo 1,3,5, respectively). In addition, more patients in PALO 1–5 reported none or mild nausea on days 6 (p= 0.023) and 7 (p= 0.139). No grade 3/4 side effects were reported. Five pts had Grade 2 constipation (PALO 1–5= 3; PALO 1,3,5 = 2), and 1 other pt in the PALO 1–5 had grade 2 headache. Conclusions: Palonosetron given on days 1, 3 and 5 or in multiple-day dosing is effective and safe for the prevention of CINV in pts with AML or HR-MDS receiving multiple-day high-dose ARA C chemotherapy. Table 1 ONDA 8 (n=32) PALO 1–5 (n=31) PALO 1,3,5 (n=32) *P=NS; QOL: Quality of Life Complete response* 8 (25) 8 (26) 10 (31) Complete control* 12 (38) 15 (49) 13 (40) Failures* 20 (63) 16 (52) 19 (59) Acute CINV* 5 (16) 1 (3) 4 (13) Delayed CINV* 15 (56) 15 (50) 15 (32) Median days with none/mid nausea* 5.43 5.83 5.58 Median days with none/little impact of emesis in QOL* 5.24 5.58 5.48

Safety and efficacy of a triple antiemetic combination with the NK-1 antagonist aprepitant (APR) in high (HEC), moderate (MEC) and high dose chemotherapy (HDC) in multiple day chemotherapy (MDC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19545-19545
Author(s):  
K. Jordan ◽  
I. Kinitz ◽  
T. Behlendorf ◽  
C. Sippel ◽  
W. Voigt ◽  
...  
Keyword(s):  
Day Treatment ◽  
Rescue Therapy ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Delayed Cinv ◽  
Loss Of Appetite ◽  
Acute Cinv ◽  
Delayed Phase

19545 Background: 5-HT3 receptor antagonists (RA) plus dexamethasone (DEX) has been shown to induce 55–57% complete responses from emesis during the 4–5 days of cisplatin chemotherapy. The role of aprepitant in MDC remains to be defined. The antiemetic triple combination of a NK-1-RA, 5-HT3-RA and dexamethasone has not been formally investigated in more than one day chemotherapy. Methods: In this retrospective study, pts. with MDC received APR 125 mg d1, 80 mg consecutive days, granisetron (GRAN) 2 mg daily and DEX 8 mg daily for prevention of acute CINV and APR 80 mg and DEX 8 mg for 2 days for delayed CINV. Endpoints were complete response (CR, no vomiting & no use of rescue therapy) in the acute, delayed and overall phase. Results: Of 103 pts. (f/m 21/82 pts.; median age 40.6y) with various types of cancers 41 pts. (39.8%) received HEC, 44 (42.8%) MEC, and 18 pts. (17.4%) HDC. Median duration of CTX was 3.42 days (HEC 3.9 d). The most frequent regimens were ICE (35%), PEB (14.6%), I3VA (10.7%), MAID (4.9%) and IEV (5.9%). Toxicity: Singultus was reported in 6.8% and loss of appetite in 25.5%. Elevation (CTC grade 1–2) of transaminase/AP/bilirubin and creatinine were seen in comparison to pretreatment values in 15.6%/6.8%/21.1% and 7.8% of all pts.. Efficacy: Acute/delayed/overall CR in HEC was 68.3%/70.7%/63.4%, in MEC 77.3%/84.1%/77.3% and in HDC 77.8%/61.6%/55.6%. Risk factor analysis revealed that pretreatment anxiety increased the risk of vomiting significantly (p= 0.008). Conclusions: Toxicity seems not to be increased by the multiple day treatment of APR (5–7 days) in comparison to the usually used 3-day APR regimen. The CR in the acute and delayed phase in patients receiving HEC was superior to the results reported in the literature with the combination of a 5-HT3 RA and DEX. The CR in the delayed phase in MEC was better than reported by Warr et al. where pts. receiving only one day of MEC and APR mono in the delayed phase. This might be due to the combination of APR/DEX in the delayed phase in our study. These promising results have to be confirmed in a prospective randomized trial. No significant financial relationships to disclose.

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