Placebo-Controlled, Double-Blinded Phase III Study Comparing Dexamethasone on Day 1 With Dexamethasone on Days 1 to 3 With Combined Neurokinin-1 Receptor Antagonist and Palonosetron in High-Emetogenic Chemotherapy

2018 ◽  
Vol 36 (10) ◽  
pp. 1000-1006 ◽  
Author(s):  
Yuka Ito ◽  
Takashi Tsuda ◽  
Hiroko Minatogawa ◽  
Sayaka Kano ◽  
Kentaro Sakamaki ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Complete Response ◽  
Emetogenic Chemotherapy ◽  
Phase Iii ◽  
Neurokinin 1 Receptor ◽  
Phase Iii Study ◽  
Neurokinin 1 ◽  
Double Blinded ◽  
To Receive

Purpose We evaluated the noninferiority of dexamethasone (DEX) on day 1, with sparing on days 2 and 3, combined with neurokinin-1 receptor antagonist (NK1-RA) and palonosetron (Palo) compared with the 3-day use of DEX in highly-emetogenic chemotherapy (HEC). Patients and Methods Patients who were scheduled to receive HEC (cisplatin ≥ 50 mg/m2 or anthracycline plus cyclophosphamide) were randomly assigned to receive either DEX on days 1 to 3 (Arm D3) or DEX on day 1 and placebo on days 2 and 3 (Arm D1) combined with NK1-RA and Palo. The primary end point was complete response (CR), defined as no emesis and no rescue medications during the overall (0 to 120 h) phase. The noninferiority margin was set at −15.0% (Arm D1 − Arm D3). Results A total of 396 patients—196 and 200 patients in Arms D3 and D1, respectively—were evaluated. CR rates during the overall period were 46.9% for Arm D3 and 44.0% for Arm D1 (95% CI, −12.6% to 6.8%; P = .007). CR rates during the acute (0 to 24 h) phase were 63.3% and 64.5% for Arms D3 and D1, respectively (95% CI, −8.1% to 10.6%; P < .001), and they were 56.6% and 51.5%, respectively, during the delayed (24 to 120 h) phase (95% CI, −14.8% to 4.6%; P = .023). Hot flushes and tremors were observed more frequently as DEX-related adverse events on days 4 and 5 in Arm D3, whereas anorexia, depression, and fatigue were observed more frequently on days 2 and 3 in Arm D1. As an indication of quality of life, global health status was similar in both arms. Conclusion Antiemetic DEX administration on days 2 and 3 can be spared when combined with NK1-RA and Palo in HEC.

Phase III Trial of Casopitant, a Novel Neurokinin-1 Receptor Antagonist, for the Prevention of Nausea and Vomiting in Patients Receiving Moderately Emetogenic Chemotherapy

2009 ◽  
Vol 27 (32) ◽  
pp. 5363-5369 ◽  
Author(s):  
Jørn Herrstedt ◽  
Wichit Apornwirat ◽  
Ahmed Shaharyar ◽  
Zeba Aziz ◽  
Fausto Roila ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Complete Response ◽  
Emetogenic Chemotherapy ◽  
Nausea And Vomiting ◽  
Phase Iii ◽  
Controlled Clinical Trial ◽  
Moderately Emetogenic Chemotherapy ◽  
Phase Iii Trial ◽  
Neurokinin 1 Receptor ◽  
Neurokinin 1

PurposeThe purpose of this phase III trial was to evaluate the efficacy and safety of regimens containing casopitant, a novel neurokinin-1 receptor antagonist, for the prevention of chemotherapy-induced nausea and vomiting during the first cycle in patients receiving moderately emetogenic chemotherapy (MEC).Patients and MethodsPredominantly female patients (98%) diagnosed with breast cancer (96%) who were chemotherapy-naïve and scheduled to receive an anthracycline and cyclophosphamide (AC) –based regimen were enrolled onto this multinational, randomized, double-blind, parallel-group, placebo-controlled clinical trial. All patients received dexamethasone 8 mg intravenously (IV) on day 1 and oral ondansetron 8 mg twice daily on days 1 to 3. Patients were randomly assigned to a control arm (placebo), a single oral dose casopitant arm (150 mg orally [PO] on day 1), a 3-day oral casopitant arm (150 mg PO on day 1 plus 50 mg PO on days 2 to 3), or a 3-day IV/oral casopitant arm (90 mg IV on day 1 plus 50 mg PO on days 2 to 3). The primary end point was the proportion of patients achieving complete response (no vomiting/retching or rescue medications) in the first 120 hours after the initiation of MEC.ResultsA significantly greater proportion of patients in the single-dose oral casopitant arm, 3-day oral casopitant arm, and 3-day IV/oral casopitant arm achieved complete response (73%, 73%, and 74%, respectively) versus control (59%; P < .0001). The study did not demonstrate a reduced proportion of patients with nausea or significant nausea in those receiving casopitant. Adverse events were balanced among study arms.ConclusionAll casopitant regimens studied were more effective than the control regimen. Casopitant was generally well tolerated.

Efficacy of Thalidomide in Preventing Delayed Nausea and Vomiting Induced by Highly Emetogenic Chemotherapy: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase III Trial (CLOG1302 study)

2017 ◽  
Vol 35 (31) ◽  
pp. 3558-3565 ◽  
Author(s):  
Lingyun Zhang ◽  
Xiujuan Qu ◽  
Yuee Teng ◽  
Jing Shi ◽  
Ping Yu ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Complete Response ◽  
Emetogenic Chemotherapy ◽  
Nausea And Vomiting ◽  
Phase Iii ◽  
Highly Emetogenic Chemotherapy ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Delayed Nausea

Purpose We examined the efficacy and safety of thalidomide (THD) for the prevention of delayed nausea and vomiting in patients who received highly emetogenic chemotherapy (HEC). Patients and Methods In a randomized, double-blind, active-controlled, phase III trial, chemotherapy-naive patients with cancer who were scheduled to receive HEC that contained cisplatin or cyclophosphamide-doxorubicin/epirubincin ≥ 50 mg/m2 regimens were randomly assigned to a THD group (100 mg twice daily on days 1 to 5) or placebo group, both with palonosetron (0.25 mg on day 1) and dexamethasone (12 mg on day 1; 8 mg on days 2 to 4). Primary end point was complete response to vomiting—no emesis or use of rescue medication—in the delayed phase (25 to 120 h). Nausea and anorexia on days 1 to 5 were evaluated by the 4-point Likert scale (0, no symptoms; 3, severe). Quality of life was assessed by the European Organization for Research and Treatment of Cancer QLQ-C30 version 3 questionnaire on days −1 and 6. Results Of 656 patients, 638 were evaluable: 317 in the THD group and 321 in the control group. Compared with placebo, delayed and overall (0 to 120 h) complete response rates to vomiting were significantly higher with THD: 76.9% versus 61.7% ( P < .001) and 66.1% versus 53.3% ( P = .001), respectively. Rates of no nausea were also higher in the THD group (delayed: 47.3% v 33.3%; P < .001; overall: 41% v 29.6%; P = .003), and mean scores of anorexia were lower overall (0.44 ± 0.717 v 0.64 ± 0.844; P = .003). Adverse effects were mild to moderate. The THD group had increased sedation, dizziness, constipation, and dry mouth, but experienced better quality of life after chemotherapy. Conclusion Thalidomide combined with palonosetron and dexamethasone significantly improved HEC-induced delayed nausea and vomiting prevention in chemotherapy-naive patients.

scholarly journals Ramosetron versus Palonosetron in Combination with Aprepitant and Dexamethasone for the Control of Highly-Emetogenic Chemotherapy-Induced Nausea and Vomiting

2020 ◽  
Vol 52 (3) ◽  
pp. 907-916 ◽  
Author(s):  
Jin Hyoung Kang ◽  
Jung Hye Kwon ◽  
Yun-Gyoo Lee ◽  
Keon Uk Park ◽  
Ho Jung An ◽  
...  
Keyword(s):  
Daily Life ◽  
Complete Response ◽  
Risk Difference ◽  
Emetogenic Chemotherapy ◽  
Nausea And Vomiting ◽  
Complete Protection ◽  
Highly Emetogenic Chemotherapy ◽  
Secondary Endpoints ◽  
To Receive

PurposeThe purpose of this study was to compare ramosetron (RAM), aprepitant (APR), and dexamethasone (DEX) [RAD] with palonosetron (PAL), APR, and DEX [PAD] in controlling highly-emetogenic chemotherapy (HEC)–induced nausea and vomiting. Materials and MethodsPatients were randomly assigned (1:1) to receive RAD or PAD:RAM (0.3 mg intravenously) or PAL (0.25 mg intravenously) D1, combined with APR (125 mg orally, D1 and 80 mg orally, D2-3) and DEX (12 mg orally or intravenously, D1 and 8 mg orally, D2-4). Patients were stratified by gender, cisplatin-based chemotherapy, and administration schedule. The primary endpoint was overall complete response (CR), defined as no emesis and no rescue regimen during 5 days of HEC. Secondary endpoints were overall complete protection (CP; CR+nausea score < 25 mm) and total control (TC; CR+nausea score < 5 mm). Quality of life was assessed by Functional Living Index Emesis (FLIE) questionnaire on D0 and D6.ResultsA total of 279 patients receiving RAD (n=137) or PAD (n=142) were evaluated. Overall CR rates in RAD and PAD recipients were 81.8% and 79.6% (risk difference [RD], 2.2%; 95% confidence interval [CI], −7.1 to 11.4), respectively. Overall CP and TC rates for RAD and PAD were 56.2% and 58.5% (RD, −2.3%; 95% CI, −13.9 to 9.4) and 47.5% vs. 43.7% (RD, 3.8%; 95% CI, −7.9 to 15.5), respectively. FLIE total score ≥ 108 (no impact on daily life) was comparable between RAD and PAD (73.9% vs. 73.4%, respectively). Adverse events were similar between the two groups.ConclusionIn all aspects of efficacy, safety and QOL, RAD is non-inferior to PAD for the control of CINV in cancer patients receiving HEC.

Phase III study of sustained release granisetron (APF530) compared to palonosetron for the prevention of chemotherapy-induced nausea and vomiting (CINV)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9627-9627 ◽  
Author(s):  
J. J. Grous ◽  
E. Riegel ◽  
N. Gabrail ◽  
V. Charu ◽  
R. Arevalo-Araujo ◽  
...  
Keyword(s):  
Acute Phase ◽  
Complete Response ◽  
Phase Iii ◽  
Sustained Drug Release ◽  
Phase Iii Study ◽  
Multiple Cycles ◽  
The Difference ◽  
To Receive ◽  
Delayed Phase ◽  
Polymeric Formulation

9627 Background: APF530 is a polymeric formulation of granisetron providing sustained drug release over 5 days. Two doses (5 and 10 mg) of subcutaneous APF530 were evaluated in comparison to 0.25 mg intravenous palonosetron. Efficacy was evaluated in acute (0–24 hrs) and delayed (24–120 hrs) CINV among patients receiving moderate (MEC) or highly (HEC) emetogenic chemotherapy. Methods: Randomized, blinded patients (n=1,395) were stratified into MEC or HEC according to Hesketh et al 1999, and assigned to receive either dose of APF530 or palonosetron. Dexamethasone use was standardized based on the emetogenic strata. Patient diaries recorded emetic episodes, nausea and rescue medications over a 5-day period. Primary endpoint was Complete Response (CR), defined as no emetic episodes and no rescue medication. Non-inferiority to palonosetron was declared if the lower bound of the CI for the difference was above -15%. Results: APF530 was well tolerated. Adverse events were consistent with those previously reported for granisetron. For APF530 Tmax was observed about 24 hrs with sustained levels over 120 hrs. For MEC acute phase CR rates of 74.8% (n=214), 76.9% (n=212) and 75.0% (n=208) were observed for 5 mg, 10 mg APF530 and palonosetron, respectively. Delayed phase CR rates of 51.4%, 59.0% and 57.7% were observed for 5 mg, 10 mg APF530 and palonosetron, respectively. For HEC acute phase CR rates of 77.7% (n=229), 81.3% (n=240) and 80.7% (n=238) were observed for 5 mg, 10 mg APF530 and palonosetron, respectively. Delayed phase CR rates of 64.6%, 68.3% and 66.4% were observed for 5 mg, 10 mg APF530 and palonosetron, respectively. Efficacy was maintained with APF530 over multiple cycles (up to 4). Conclusions: Both doses of APF530 were non-inferior to palonosetron with respect to CR during the acute phase following MEC and HEC. Only the higher dose of APF530 (10 mg granisetron) was non-inferior to palonosetron during the delayed phase of MEC. Both doses of APF530 were comparable to the CR rates of palonosetron during the delayed phase of HEC. [Table: see text]

A phase III study comparing amrubicin and cisplatin (AP) with irinotecan and cisplatin (IP) for the treatment of extended-stage small cell lung cancer (ED-SCLC): JCOG0509.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7003-7003 ◽  
Author(s):  
Yoshikazu Kotani ◽  
Miyako Satouchi ◽  
Masahiko Ando ◽  
Kazuhiko Nakagawa ◽  
Nobuyuki Yamamoto ◽  
...  
Keyword(s):  
Standard Treatment ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Severe Diarrhea ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Ecog Ps ◽  
To Receive

7003 Background: IP is the standard treatment for ED-SCLC, however often cause severe diarrhea. AP have shown promising activity in SCLC with fewer diarrhea. We conducted a phase III trial comparing AP with IP. Methods: Eligibility criteria included patients (pts) with chemotherapy-naïve, ED-SCLC, aged 20 to 70, and ECOG PS 0-1. Pts were randomized to receive either IP or AP, balancing for site, sex, and PS. IP comprised administration of I (60 mg/m2) iv on days 1, 8, and 15, and P (60 mg/m2) iv on day1,every 4 weeks. AP comprised administration of A (40 mg/m2) iv on day 1-3, and P (60 mg/m2) iv on day1, every 3 weeks. The planned sample size was 141 pts in each arm with a one-sided alpha of 5% and power of 70% and a non-inferiority margin of hazard ratio (HR) as 1.31. The primary endpoint was overall survival (OS). The secondary endpoints were response rate (RR), progression-free survival (PFS), adverse events (AEs), and quality of life (QOL). We evaluated pts’ QOL twice: at the baseline and after completion of the second course. Results: 284 pts were randomized to IP (n=142) and AP (n=142). Median age was 63, 84% were male, and 56% had PS 0. When 191pts enrolled, more febrile neutropenia (FN) was observed in AP than anticipated, and the initial dose of A was decreased from 40 mg/m2 to 35 mg/m2. At the second interim analysis conducted after the completion of patient accrual, the median OS of AP (15.0 m) was much worse than that of IP (18.3 m) and the HR (1.41; 96.3% CI, 1.03-1.93) exceeds even the non-inferiority margin, so the Data and Safety Monitoring Committee recommended early publication of the results. Median PFS was 5.7 (IP) vs. 5.2 months (AP) (HR 1.43, 95% CI, 1.13-1.82). RR was 69.5% (IP) vs. 77.9% (AP) (p=0.14). AEs in IP and AP arm were Grade 4 neutropenia (22.5% vs. 78.6%), G3-4 FN (10.7% vs. 32.1%), and G3-4 diarrhea (7.1% vs.1.4%). Proportion of improvement in physical status of QOL was 37.1%(IP) vs. 31.7%(AP), (odds ratio 0.72; 95%CI, 0.43-1.22; P=0.227). Conclusions: AP showed more bone marrow suppression than expected although it caused less diarrhea. The non-inferiority of AP to IP was not demonstrated and IP remains the standard treatment for ED-SCLC.

Phase III Study of Two Different Dosing Schedules of Erythropoietin in Anemic Patients With Cancer

2006 ◽  
Vol 24 (7) ◽  
pp. 1079-1089 ◽  
Author(s):  
David P. Steensma ◽  
Roy Molina ◽  
Jeff A. Sloan ◽  
Daniel A. Nikcevich ◽  
Paul L. Schaefer ◽  
...  
Keyword(s):  
Maintenance Phase ◽  
Drug Dose ◽  
Phase Iii ◽  
Epoetin Alfa ◽  
Patients With Cancer ◽  
Global Quality ◽  
Global Quality Of Life ◽  
Phase Iii Study ◽  
To Receive

PurposeTo compare maintenance epoetin alfa administered once every 3 weeks with continued weekly epoetin alfa for patients with cancer-associated anemia.Patients and MethodsEligible patients were randomly assigned at enrollment to receive three weekly doses of epoetin alfa 40,000 U subcutaneously (SC), followed by either standard weekly epoetin alfa (40K arm) or 120,000 U of epoetin alfa (120K arm) SC every 3 weeks for 18 additional weeks.ResultsThree hundred sixty-five patients were enrolled. One hundred eighty-three patients were assigned to the 40K arm, and 182 were assigned to the 120K arm. There was no difference in the proportion of patients requiring transfusions during the study (23% in 40K arm and 18% in 120K arm, P = .22) or specifically during the maintenance phase (13% in 40K arm v 15% in 120K arm, P = .58). Patients randomly assigned to the 40K arm were more likely to have a ≥ 2 or ≥ 3 g/dL hemoglobin (Hb) increment, were more likely to have a drug dose held because of high Hb, and had higher mean end-of-study Hb levels. Toxicities, including thromboembolism, and overall survival were similar. Patients in the 40K arm had a higher global quality of life (QOL) at baseline for unclear reasons, whereas patients in the 120K arm had a greater global QOL improvement during the study, so end-of-study QOL was equivalent.ConclusionAfter three weekly doses of epoetin alfa 40,000 U, a dose of 120,000 U can be administered safely once every 3 weeks without increasing transfusion needs or sacrificing QOL. The Hb increment is somewhat greater with continued weekly epoetin alfa. Lack of blinding as a result of different treatment schedules may have confounded results.

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