Rolapitant for control of chemotherapy-induced nausea and vomiting (CINV) in patients with gynecologic cancer.

2016 ◽  
Vol 34 (26_suppl) ◽  
pp. 223-223 ◽  
Author(s):  
Bernardo Leon Rapoport ◽  
Lee Steven Schwartzberg ◽  
Sujata Arora ◽  
Daniel Powers ◽  
Karin Jordan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Receptor Antagonist ◽  
Rescue Medication ◽  
Gynecologic Cancer ◽  
Complete Response ◽  
Double Blind ◽  
Neurokinin 1 ◽  
Long Acting ◽  
Type 3 ◽  
And Control

223 Background: Rolapitant, a long-acting neurokinin-1 receptor antagonist, protected against CINV in patients receiving highly or moderately emetogenic chemotherapy (HEC or MEC). Methods: In 3 double-blind phase 3 studies, patients were randomized to receive oral rolapitant 180 mg or placebo before administration of HEC or MEC. All patients received a 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone. In a post hoc analysis of 3 pooled studies (2 HEC and 1 MEC), we assessed the efficacy and safety of rolapitant in patients with gynecologic (ovarian, uterine, or cervical) cancer. Endpoints included complete response (CR; no emesis and no use of rescue medication), no emesis, no nausea (maximum visual analogue scale [VAS] < 5 mm), and complete protection (CP; no emesis, no use of rescue medication, and no significant nausea [maximum VAS < 25 mm]) in the overall (0–120 h), acute (≤ 24 h), and delayed (> 24–120 h) phases. Results: Of 201 patients with gynecologic cancer (60% ovarian, 28% uterine, and 12% cervical cancer), 55% received cisplatin-based HEC and 44% received MEC (99% of whom received carboplatin-based therapy). In the overall and delayed phases, improved rates of CR, no emesis, no nausea, and CP were observed with rolapitant compared with control (Table). The overall incidence of treatment-emergent adverse events was similar in the rolapitant and control groups (45% vs 54%). Conclusions: Rolapitant protected against overall and delayed CINV in patients with gynecologic cancer receiving HEC or MEC. Clinical trial information: NCT01500226, NCT01499849, NCT01500213. [Table: see text]

Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of highly or moderately emetogenic chemotherapy (HEC, MEC).

2015 ◽  
Vol 33 (29_suppl) ◽  
pp. 210-210 ◽  
Author(s):  
Bernardo Leon Rapoport ◽  
Lee Steven Schwartzberg ◽  
Martin Robert Chasen ◽  
Daniel Powers ◽  
Sujata Arora ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Active Control ◽  
Pooled Analysis ◽  
Emetogenic Chemotherapy ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Multiple Cycles ◽  
Neurokinin 1 ◽  
Long Acting ◽  
And Control

210 Background: The long-acting neurokinin-1 receptor antagonist (NK-1 RA) rolapitant has demonstrated efficacy for CINV prevention in patients receiving HEC and MEC during Cycle 1. The efficacy and safety of rolapitant was examined during subsequent cycles 2–6 in a pooled analysis. Methods: In 4 double-blind, active-controlled studies, patients were randomized to oral rolapitant 180 mg or placebo 1–2 hours before chemotherapy. All patients received active control: 5HT3 receptor antagonist + oral dexamethasone. Patients completing Cycle 1 could receive the same anti-emetic treatment in subsequent cycles. On Days 6-8 of subsequent cycles, patients self-reported the incidence of emesis, or of nausea interfering with normal daily life following Day 1 of chemotherapy. Results: A greater proportion of patients on rolapitant than on active control reported no emesis or interfering nausea separately for each subsequent cycle. Results of individual studies and pooled analysis are shown in the Table. During cycles 2-6, the incidence of treatment-related adverse events (AEs) was similar for rolapitant (5.5%) and control (6.8%). The most common treatment-related AEs were similar in both arms: constipation (rolapitant: 1.2%; control: 0.8%) and fatigue (rolapitant: 1.3%; control: 1.8%). Conclusions: Rolapitant was superior to active control in reducing CINV when administered over multiple cycles of moderately or highly emetogenic chemotherapy, with no increase in toxicity. Clinical trial information: NCT00394966 - NCT01500213 - NCT01500226 - NCT01499849. [Table: see text]

Efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with gastrointestinal and colorectal cancers.

2016 ◽  
Vol 34 (26_suppl) ◽  
pp. 222-222
Author(s):  
Rudolph M. Navari ◽  
Karin Jordan ◽  
Bernardo Leon Rapoport ◽  
Ian D. Schnadig ◽  
Martin Chasen ◽  
...  
Keyword(s):  
Active Control ◽  
Rescue Medication ◽  
Complete Response ◽  
Emetogenic Chemotherapy ◽  
Colorectal Cancers ◽  
Dexamethasone Therapy ◽  
Neurokinin 1 ◽  
Long Acting ◽  
Type 3 ◽  
Significant Nausea

222 Background: Rolapitant (VARUBI) is a selective, long-acting neurokinin-1 receptor antagonist (RA) for the prevention of CINV. Rolapitant effectively prevented CINV in phase 3 trials of patients (pts) receiving highly or moderately emetogenic chemotherapy (HEC, MEC). While MEC and HEC regimens are commonly used to treat pts with gastrointestinal and colorectal cancers (GI/CRC), very few studies have evaluated the effectiveness of a neurokinin-1 RA regimen in these pts. We assessed the incidence of CINV and efficacy of rolapitant in a subset of pts with GI/CRC. Methods: This is a post hoc analysis of 3 similarly-designed, randomized, placebo-controlled trials. Pts with cancer of the esophagus, stomach, colon/rectum, or anus received a single oral dose of 180 mg oral rolapitant or placebo prior to HEC or MEC. All pts received a 5-hydroxytryptamine type 3 (5-HT3) RA and dexamethasone (active control). The HEC studies included cisplatin, and the MEC study carboplatin, oxaliplatin, irinotecan, epirubicin, and doxorubicin. Endpoints included complete response (CR; no emesis and no use of rescue medication), no emesis, no nausea (maximum visual analogue scale [VAS] < 5 mm), no significant nausea (maximum VAS < 25mm) and complete protection (CP; no emesis, no use of rescue medication, and no significant nausea) in the overall (0-120 h), acute (≤ 24 h), and delayed (> 24-120 h) phases. Results: Out of 188 GI/CRC pts, 101 pts received rolapitant and 87 received active control. Pts treated with rolapitant had significantly higher rates of CR, no nausea, no emesis, and CP in the overall phase (P < 0.05). Rolapitant was well-tolerated and overall incidence of treatment-emergent adverse events comparable in both groups. Conclusions: Addition of rolapitant to 5-HT3RA and dexamethasone therapy significantly improved CR, no nausea, no emesis, and CP in pts with GI/CRC receiving emetogenic chemotherapy. Clinical trial information: NCT01500226, NCT01499849, NCT01500213. [Table: see text]

Randomized phase II trial of the neurokinin-1 receptor antagonist (NK-1 RA) casopitant mesylate with ondansetron (ond)/dexamethasone (dex) for chemotherapy-induced nausea/vomiting (CINV) in patients (pts) receiving highly emetogenic chemotherapy (HEC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8513-8513 ◽  
Author(s):  
J. Rolski ◽  
R. Ramlau ◽  
M. Dediu ◽  
M. W. Russo ◽  
G. A. Ross ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Complete Response ◽  
Trend Test ◽  
Placebo Control ◽  
Double Blind ◽  
Therapy Regimen ◽  
Armitage Trend Test ◽  
Neurokinin 1 ◽  
Intent To Treat ◽  
Future Evaluation

8513 Background: A combination of a 5-HT3 receptor antagonist (5-HT3 RA) + dex is standard for prevention of CINV due to HEC. However, NK-1 RAs are now also of interest. The current trial evaluated casopitant mesylate, a potent, oral, selective NK-1 RA, in a triple therapy regimen with a 5-HT3 RA and dex in pts receiving HEC. Methods: In this multicenter, randomized, double-blind, placebo-controlled, dose-ranging, parallel group study, pts receiving HEC were stratified by gender and randomized among six arms. HEC consisted of regimens including cisplatin ≥ 70 mg/m2 IV over 1–4 hours (h) day 1 (D1). All pts received ond 32mg IV D1 and dex PO D1–4 with either placebo control, casopitant 50mg QD D1–3, casopitant 100mg QD D1–3, or casopitant 150mg QD D1–3. Pts on exploratory arms received ond/dex plus either casopitant 150 mg D1 only or aprepitant 125mg D1 and 80mg D2–3. The primary endpoint was complete response (CR) rate (no vomiting, retching, rescue medications or premature withdrawals) during the first 120 h following initiation of HEC. Target intent-to-treat (ITT) group enrollment was 82 pts per arm. Results: 493 enrolled patients comprised the ITT group. CR rate was 60% in the control arm; 76% for casopitant 50mg; 86% for 100mg; and 77% for 150mg (p=.0036, Cochran-Armitage trend test). CR rate was 75% with casopitant 150 mg D1 and 72% for 3-day aprepitant. CR rates at 24 h were similar in all groups (86%-96%). Casopitant prolonged time to emesis (p=.0029) and increased the proportion of pts without vomiting (p=.0122) relative to control. There were no differences in rates of nausea or use of rescue medication among groups. Adverse events were similar across all arms, with neutropenia, nausea, and hiccups (≤ 17%) as most common. All casopitant doses were generally well tolerated. Conclusions: The addition of casopitant to ond/dex at all doses tested and in 1- or 3-day administration regimens was well tolerated and significantly reduced CINV rates over a 5-day period in pts receiving HEC. The results of the exploratory 1-day regimen are of particular interest for future evaluation. [Table: see text]

scholarly journals A Comparison of Fosaprepitant and Ondansetron for Preventing Postoperative Nausea and Vomiting in Moderate to High Risk Patients: A Retrospective Database Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Chiaki Murakami ◽  
Nami Kakuta ◽  
Katsuyoshi Kume ◽  
Yoko Sakai ◽  
Asuka Kasai ◽  
...  
Keyword(s):  
General Anesthesia ◽  
Receptor Antagonist ◽  
Postoperative Nausea ◽  
Postoperative Nausea And Vomiting ◽  
Complete Response ◽  
Nausea And Vomiting ◽  
Nk1 Receptor Antagonist ◽  
Risk Patients ◽  
Neurokinin 1 ◽  
Type 3

Postoperative nausea and vomiting (PONV) occur in 30–50% of patients undergoing general anesthesia and in 70–80% of high PONV risk patients. In this study, we investigated the efficacy of fosaprepitant, a neurokinin-1 (NK1) receptor antagonist, compared to ondansetron, a selective 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, in moderate to high PONV risk patients from our previous randomized controlled trials. Patients (171 patients from 4 pooled studies) with the Apfel simplified score ≥ 2 and undergoing general anesthesia were randomly allocated to receive intravenous fosaprepitant 150 mg (NK1 group, n=82) and intravenous ondansetron 4 mg (ONS group, n=89) before induction of anesthesia. Incidence of vomiting was significantly lower in the NK1 group compared to the ONS group 0–2, 0–24, and 0–48 hours after surgery (2 versus 17%, 2 versus 28%, and 2 versus 29%, resp.). However, no significant differences in PONV, complete response, rescue antiemetic use, and nausea score were observed between groups 0–48 hours after surgery. In moderate to high PONV risk patients, fosaprepitant decreased the incidence of vomiting and was superior to ondansetron in preventing postoperative vomiting 0–48 hours after surgery.

Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients (pts) receiving anthracycline-cyclophosphamide (AC)-based chemotherapy.

2015 ◽  
Vol 33 (29_suppl) ◽  
pp. 208-208
Author(s):  
Daniel Powers ◽  
Ian D. Schnadig ◽  
Manuel R. Modiano ◽  
Sujata Arora ◽  
Lee Steven Schwartzberg
Keyword(s):  
Active Control ◽  
Rescue Medication ◽  
Complete Response ◽  
Controlled Study ◽  
Highly Emetogenic Chemotherapy ◽  
Double Blind ◽  
Post Hoc ◽  
And Control ◽  
Significant Nausea ◽  
Clinical Trial Information

208 Background: Rolapitant, a novel NK-1 receptor antagonist, demonstrated efficacy in the prevention of CINV in pts receiving moderately- or highly emetogenic chemotherapy (MEC; HEC). In this post-hoc analysis, we evaluated safety and efficacy outcomes in pts receiving AC-based therapy, now considered HEC. Methods: This double-blind, active-controlled study randomized pts to oral rolapitant 180 mg plus granisetron 2 mg and dexamethasone 20 mg or granisetron/dexamethasone alone (active control). Complete response (CR = no emesis and no use of rescue medication), no emesis, no significant nausea, and time to emesis or rescue medication during overall, acute, and delayed phases and treatment-emergent adverse events (AEs) are presented. Results: 703 pts received AC-based therapy, of which 97% had breast cancer. CR was significantly higher for rolapitant vs. active control for delayed and overall phases in pts receiving AC-based therapy (Table). Time to first emesis or use of rescue medication was significantly longer with rolapitant vs. active control (between-group comparison, p = 0.032); median was not reached in either treatment arm. A significantly greater proportion of pts on rolapitant (73.0%) vs. active control (60.2%) had no emesis during the overall phase (p < 0.001). Rates of no significant nausea were similar for rolapitant (63.7%) and active control (62.4%) in the overall phase (p = 0.728). Treatment-related AEs (TRAEs) during Cycle 1 occurred in 8.7% and 8.8% of pts on rolapitant vs. active control. Most frequent TRAEs were constipation (2.9% vs. 2.7%), fatigue (2.3% vs. 2.2%), and headache (2.3% vs. 3.3%). Conclusions: Rolapitant was superior to active control in preventing CINV during delayed and overall phases after AC-based chemotherapy. The safety profiles of the rolapitant and control arms were similar. These results are consistent with those of the overall pt population in this study. Clinical trial information: NCT01500226. [Table: see text]

scholarly journals Single-dose netupitant/palonosetron versus 3-day aprepitant for preventing chemotherapy-induced nausea and vomiting: a pooled analysis

2021 ◽  
Author(s):  
Rudolph M Navari ◽  
Gary Binder ◽  
Erminio Bonizzoni ◽  
Rebecca Clark-Snow ◽  
Silvia Olivari ◽  
...  
Keyword(s):  
Rescue Medication ◽  
Complete Response ◽  
Pooled Analysis ◽  
Nausea And Vomiting ◽  
Complete Protection ◽  
Efficacy Data ◽  
Delayed Nausea ◽  
Neurokinin 1 ◽  
Type 3 ◽  
Significant Nausea

Aim: In the absence of comparative studies, guidelines consider neurokinin 1 receptor antagonists (RAs) as interchangeable. We evaluated the pooled efficacy from three cisplatin registration trials, each with arms containing netupitant/palonosetron (NEPA), a fixed neurokinin 1 RA (netupitant)/serotonin Type 3 (5-HT3) RA (palonosetron) combination, and an aprepitant (APR) regimen. Materials & methods: Efficacy data were pooled for rates of complete response (CR: no emesis/no rescue medication), complete protection (CR + no significant nausea), total control (CR + no nausea) and no significant nausea during acute (0–24 h), delayed (>24–120 h) and overall (0–120 h) phases post chemotherapy. Results: Among 621 NEPA and 576 APR patients, response rates were similar for the acute phase, and generally favored NEPA during delayed and overall phases. CR rates for NEPA versus APR were 88.4 versus 89.2%, 81.8 versus 76.9% (p < 0.05) and 78.4 versus 75.0% during the acute, delayed and overall phases, respectively. Conclusion: Oral NEPA administered on day 1 was more effective than a 3-day APR regimen in preventing delayed nausea and vomiting associated with cisplatin.

The dipeptide neurokinin-1 receptor antagonist S19752 is a potent and long-acting inhibitor of bronchoconstriction when administered by aerosol to the guinea pig in vivo

1997 ◽  
Vol 7 (2) ◽  
pp. 203-208 ◽  
Author(s):  
Jean-Luc Fauchère ◽  
Nathalie Kucharczyk ◽  
Edgar Jacoby ◽  
Michel Lonchampt ◽  
Pascale Robineau ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Receptor Antagonist ◽  
Neurokinin 1 Receptor ◽  
Neurokinin 1 ◽  
Long Acting

Exploratory randomized trial to evaluate the effect of indisetron tablets for preventing chemotherapy-induced nausea and vomiting (CINV)/acute-onset diarrhea induced by IRIS/FOLFIRI: HGCSG0704.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 624-624
Author(s):  
Sosuke Kato ◽  
Hiraku Fukushima ◽  
Kanji Kato ◽  
Satoshi Yuki ◽  
Kazuaki Harada ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Rescue Medication ◽  
Complete Response ◽  
Acute Onset ◽  
Complete Protection ◽  
Primary Endpoints ◽  
Significant Difference ◽  
Secondary Endpoints ◽  
Colorectal Cancer Patients ◽  
Ecog Ps

624 Background: Indisetron is a 5-HT3 receptor antagonist that also antagonizes 5-HT4receptors. Indisetron tablets showed the non-inferiority to ondansetron tablets in terms of efficacy for preventing CINV. Moreover, preclinical data administered with irinotecan showed indisetron significantly reduced stool frequency in mice and inhibited the colonic peristalsis in dogs. We designed a pilot study compared with granisetron in the efficacy and tolerability of indisetron for irinotecan-induced nausea, vomiting and especially in diarrhea. Methods: Advanced colorectal cancer patients treated with FOLFIRI or IRIS (Irinotecan + S-1) with or without bevacizumab were enrolled in this study. Treatment: Arm A: indisetron tablets 8mg po day1. Arm B: granisetron 3mg iv day 1. The primary endpoints were the incidence of acute-onset diarrhea and complete protection from vomiting. Secondary endpoints were tolerability, complete protection from nausea and rate of no rescue medication. Results: Between May 2008 and July 2012, 33 patients (pts) were randomized. The study was closed prematurely due to poor accrual. Arm A: 16 pts, arm B 17 pts. Median age A: 68 y.o., B: 66 y.o.: ECOG PS 0/1: A: 12/4, B: 14/3pts. There was no significant difference of the incidence of acute-onset diarrhea between both groups (18.8% in A vs. 35.3% in B, p = 0.438). The proportion of complete protection from vomiting was 87.5% in A and 88.2% in B (p = 1.000). Similarly, complete protection from nausea, rate of no rescue medication, proportion of patients with a complete response (defined as no emetic episodes and no rescue medication) did not have a significant difference. Severity of nausea/vomiting and AE induced by 5-HT3 receptor antagonist were also similar between two groups. Conclusions: Compared with granisetron, indisetron showed effective and feasible results for preventing CINV induced by FOLFIRI or IRIS. Indisetron had also not improved the incidence of acute-onset diarrhea induced by irinotecan. Clinical trial information: UMIN000010162.

scholarly journals Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update

2011 ◽  
Vol 29 (31) ◽  
pp. 4189-4198 ◽  
Author(s):  
Ethan Basch ◽  
Ann Alexis Prestrud ◽  
Paul J. Hesketh ◽  
Mark G. Kris ◽  
Petra C. Feyer ◽  
...  
Keyword(s):  
Systematic Review ◽  
Receptor Antagonist ◽  
Clinical Oncology ◽  
Cochrane Collaboration ◽  
Complete Response ◽  
Large Trial ◽  
Neurokinin 1 ◽  
Chemotherapy Patients ◽  
American Society ◽  
The Cochrane Collaboration

Purpose To update the American Society of Clinical Oncology (ASCO) guideline for antiemetics in oncology. Methods A systematic review of the medical literature was completed to inform this update. MEDLINE, the Cochrane Collaboration Library, and meeting materials from ASCO and the Multinational Association for Supportive Care in Cancer were all searched. Primary outcomes of interest were complete response and rates of any vomiting or nausea. Results Thirty-seven trials met prespecified inclusion and exclusion criteria for this systematic review. Two systematic reviews from the Cochrane Collaboration were identified; one surveyed the pediatric literature. The other compared the relative efficacy of the 5-hydroxytryptamine-3 (5-HT3) receptor antagonists. Recommendations Combined anthracycline and cyclophosphamide regimens were reclassified as highly emetic. Patients who receive this combination or any highly emetic agents should receive a 5-HT3 receptor antagonist, dexamethasone, and a neurokinin 1 (NK1) receptor antagonist. A large trial validated the equivalency of fosaprepitant, a single-day intravenous formulation, with aprepitant; either therapy is appropriate. Preferential use of palonosetron is recommended for moderate emetic risk regimens, combined with dexamethasone. For low-risk agents, patients can be offered dexamethasone before the first dose of chemotherapy. Patients undergoing high emetic risk radiation therapy should receive a 5-HT3 receptor antagonist before each fraction and for 24 hours after treatment and may receive a 5-day course of dexamethasone during fractions 1 to 5. The Update Committee noted the importance of continued symptom monitoring throughout therapy. Clinicians underestimate the incidence of nausea, which is not as well controlled as emesis.

Effects of anemia correction with epoetin beta in patients receiving radiochemotherapy for advanced cervical cancer

2008 ◽  
Vol 18 (3) ◽  
pp. 515-524 ◽  
Author(s):  
H.-G. STRAUSS ◽  
G. HAENSGEN ◽  
J. DUNST ◽  
C. R.W. HAYWARD ◽  
H.-U. BURGER ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Overall Survival ◽  
Treatment Failure ◽  
Complete Response ◽  
Control Groups ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Epoetin Beta ◽  
End Point ◽  
And Control

Patients with cervical cancer frequently suffer from anemia. This two-stage, adaptive-design study investigated the effect of anemia correction with epoetin beta on treatment outcomes. Patients with stage IIB–IVA cervical cancer received radiochemotherapy (RCT) and were randomized to epoetin 150 IU/kg three times weekly (n = 34) or standard care (control; n = 40) for up to 12 weeks. Primary end point for stage 1 aimed to establish a correlation between anemia correction and treatment failure (no complete response or relapsing within 6 months after RCT initiation) as a proof of concept before moving into stage 2. Secondary end points included progression/relapse-free survival, overall survival, response to RCT, hemoglobin (Hb) response, and safety. Median baseline Hb was 11.4 and 11.6 g/dL in epoetin and control groups, respectively. At treatment end point, median Hb increased by 1.3 g/dL with epoetin, but decreased by 0.7 g/dL in the control group (P < 0.0001). No significant correlation between Hb increase and treatment failure was demonstrated. There were no significant differences between epoetin and control groups in progression/relapse-free survival (29.4% vs 32.5% patients with events; P = 0.96), overall survival (23.5% vs 12.5% patients with events; P = 0.22) or overall complete response (53% vs 58%; P = 0.86). Adverse events were well matched between groups. This study shows that epoetin beta rapidly, effectively, and safely increases Hb levels in patients with cervical cancer receiving RCT. No positive correlation of Hb increase and improvement in clinical outcomes could be demonstrated.

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