Olanzapine for Prevention of Vomiting in Children and Adolescents Receiving Highly Emetogenic Chemotherapy: Investigator-Initiated, Randomized, Open-Label Trial

2020 ◽  
Vol 38 (32) ◽  
pp. 3785-3793 ◽  
Author(s):  
Ramavath D. Naik ◽  
Sreenivas V ◽  
Vishwajeet Singh ◽  
Ashwati S. Pillai ◽  
Deepa Dhawan ◽  
...  
Keyword(s):  
Safety Evaluation ◽  
Complete Response ◽  
Primary Objective ◽  
Emetogenic Chemotherapy ◽  
Control Group ◽  
Study Group ◽  
Open Label ◽  
Highly Emetogenic Chemotherapy ◽  
Acute Period ◽  
Open Label Trial

PURPOSE Chemotherapy-induced nausea and vomiting (CINV) is a significant toxicity of chemotherapy. Olanzapine is recommended in adult patients for the prevention of CINV but has not been prospectively investigated in children. METHODS This investigator-initiated, randomized, open-label trial evaluated olanzapine in children (ages 5-18 years) scheduled to receive the first cycle of highly emetogenic chemotherapy (HEC). All participants received aprepitant, ondansetron, and dexamethasone during and 2 days after chemotherapy. Participants in the study group additionally received oral olanzapine 0.14 mg/kg/day (rounded to the nearest 2.5 mg; maximum, 10 mg) during the chemotherapy block and 3 days postchemotherapy. The primary objective was to compare complete response (CR) rates (no vomiting and no rescue medication) between the groups in the acute, delayed, and overall periods. Nausea comparison and safety evaluation were secondary and additional objectives, respectively. The collection of outcomes and adverse events was performed daily until the completion of the overall period. RESULTS A total of 240 patients underwent randomization. We performed a modified intention-to-treat analysis on 231 patients (116 in the control group and 115 in the study group). A higher proportion of patients in the olanzapine group achieved CR in the acute period (78% v 59%; P = .001), delayed period (74% v 47%; P < .001) and overall period (64% v 38%; P < .001) than in the control group. The proportion of patients with no nausea was significantly higher in the olanzapine group in the acute period (74% v 52%; P < .001), delayed period (74% v 47%; P < .001), and overall period (64% v 37%; P < .001). Grade 1/2 somnolence was greater in the olanzapine group (35% v 11%; P < .001). There was no grade 3/4 somnolence reported. CONCLUSION Olanzapine significantly improved CR rates for vomiting in children receiving the first cycle of HEC.

Chemotherapy-Induced Nausea and Vomiting (CINV) in Hematologic Malignancy Patients Receiving Multi-Day Highly Emetogenic Chemotherapy (HEC)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2410-2410
Author(s):  
Lee S. Schwartzberg ◽  
Eric J. Roeland ◽  
Paul J.E. Miller ◽  
Mark S. Walker
Keyword(s):  
Research Funding ◽  
Hematologic Malignancy ◽  
Day Treatment ◽  
Complete Response ◽  
Primary Objective ◽  
Emetogenic Chemotherapy ◽  
Nausea And Vomiting ◽  
High Dose ◽  
Cell Transplant ◽  
Highly Emetogenic Chemotherapy

Abstract INTRODUCTION Despite recent advances in CINV prophylaxis, many questions remain unanswered including optimal treatment for hematologic malignancy (HM) patients receiving multi-day chemotherapy regimens. As preparation for stem cell transplant (SCT) and for high grade HM, highly emetogenic chemotherapy (HEC) containing regimens are often utilized. International guidelines recommend a three-drug combination of a 5-HT3receptor antagonist (5-HT3 RA), an NK-1 receptor antagonist (NK-1 RA) and dexamethasone (dex) before HEC. Little is known about CINV prevention in HM multi-day regimens. METHODS We conducted a prospective observational study in U.S. research centers with expertise in HM and SCT surveying providers and adult patients receiving up to 7 consecutive days of chemotherapy including at least one HEC drug. Those receiving concurrent radiation therapy were excluded as were patients taking antiemetics or having nausea and vomiting prior to initiation of chemotherapy. Patients completed a diary and a modified Functional Living Index - Emesis (FLIE) questionnaire daily, beginning at screening, during chemotherapy, and for up to 5 days after the last day of treatment. Daily use of scheduled antiemetics and rescue medication was collected. The primary objective was to survey patterns of CINV care for multi-day chemotherapy in HM and assess efficacy of the intervention. RESULTS Seventy-six patients were enrolled at 5 centers (range 8 -25 patients per center) between May 2015 and February 2016. Of the patients, 72 underwent pre-SCT conditioning and 4 multi-day chemotherapy for HM. Forty-nine (68%) were male and 58 (81%) were Caucasian; median age was 58 (range 22-74). The most common diagnoses were NHL, 27 (36%); multiple myeloma, 19 (25%); and AML, 15 (20%). Seventy-one patients completed all surveys. All received ≥ 1 HEC drug on day 1. The most common chemotherapy regimens were BEAM, 28 (37%), high-dose melphalan, 18 (26%), melphalan, fludarabine, and campath, 8 (11%) and fludarabine and cyclophosphamide, 4 (5%). Anti-emetic therapy was highly variable, both prior to day 1 chemotherapy and throughout multi-day treatment. On day 1 the most common regimens included: a combination of 5-HT3 RA, NK-1 RA, dex in 28 (37%); 5-HT3 RA + dex in 24 (32%); 5-HT3 RA alone in 9 (12%); 5-HT3 RA and metoclopramide in 2 (3%); other 10 (13%) and none documented 3 (4%). Complete response rate (defined as no vomiting and no use of rescue medications) was observed in 15 patients (20%); complete response by day ranged from 95% on day 1 to 46% on end of study day (p=0.041). Mean±SD nausea scores by FLIE increased from 19.9±3.1 pretreatment to 22.4±3.3 overall (p=0.0031). CONCLUSION Approaches to CINV in SCT and HM patients receiving multi-day HEC regimens are highly variable. A large majority of patients receiving multi-day chemotherapy are not achieving adequate control of nausea or vomiting. Additional clinical trials and development of evidence-based approaches to CINV prophylaxis in HM patients throughout multi-day chemotherapy are critical to improve supportive care. Disclosures Schwartzberg: Helsinn: Consultancy, Research Funding; Eisai: Consultancy; Tesaro: Consultancy; Heron: Consultancy. Roeland:Teva: Speakers Bureau; Insys: Consultancy; Helsinn: Consultancy; Heron: Consultancy; AstraZeneca: Consultancy, Research Funding; Eisai: Speakers Bureau.

scholarly journals Open-label observational study to assess the efficacy and safety of aprepitant for chemotherapy-induced nausea and vomiting prophylaxis in Indian patients receiving chemotherapy with highly emetogenic chemotherapy/moderately emetogenic chemotherapy regimens

2015 ◽  
Vol 04 (01) ◽  
pp. 007-010 ◽  
Author(s):  
Sachin Hingmire ◽  
Nirmal Raut
Keyword(s):  
Rescue Medication ◽  
Complete Response ◽  
Emetogenic Chemotherapy ◽  
Nausea And Vomiting ◽  
Efficacy And Safety ◽  
Moderately Emetogenic Chemotherapy ◽  
Open Label ◽  
Highly Emetogenic Chemotherapy ◽  
Serious Adverse Events ◽  
Complete Control

Abstract Context: Currently, there is limited data on the prevention of chemotherapy-induced nausea and vomiting (CINV) in Indian population with aprepitant containing regimens. Aims: The aim was to assess the Efficacy and Safety of Aprepitant for the prevention of nausea and vomiting associated with highly emetogenic chemotherapy/moderately emetogenic chemotherapy (HEC/MEC) regimens. Settings and Design: Investigator initiated, multicentric, open-label, prospective, noncomparative, observational trial. Subjects and Methods: Triple drug regimen with aprepitant, palonosetron, and dexamethasaone administration was assessed for the prevention of CINV during acute, delayed, and the overall phase (OP) for HEC/MEC Regimens. The primary endpoint was complete response (CR; no emesis and no use of rescue medication) and the key secondary endpoint was the complete control (CC; no emesis, no rescue medication and no more than mild nausea) during the OP. Statistical Analysis Used: Perprotocol efficacy was analyzed for the first cycle with results represented in terms of CR/CC rates using descriptive statistics. Results: Seventy-five patients were included in the study with median age of 49.7 years and 89.7% being females. The CR rate (OP) for patients administered HEC or MEC regimens during the first cycle were 92% and 90.9%, respectively. Similarly, the CC rates (OP) were 75% and 90% for these regimens, respectively. 7 (9.2%) patients reported adverse drug reactions that were mild and transient with no reports of any serious adverse events. Conclusions: Use of aprepitant containing regimen for patients receiving HEC/MEC regimen resulted in significantly high CR and CC response rates, which further consolidate its potential role to improve patient quality of life and compliance to disease management.

A prospective multicenter, single blinded, randomized phase III trial to compare the efficacy of ramosetron, aprepitant and dexamethasone with ondansetron, aprepitant, and dexamethasone for preventing chemotherapy-induced nausea and vomiting: KCSG PC10-21.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9633-9633
Author(s):  
Hyo Jung Kim ◽  
Eun-Kee Song ◽  
Jun Suk Kim ◽  
Jin Seok Ahn ◽  
Hwan Jung Yun ◽  
...  
Keyword(s):  
Complete Response ◽  
Emetogenic Chemotherapy ◽  
Nausea And Vomiting ◽  
Phase Iii ◽  
Combination Regimen ◽  
Highly Emetogenic Chemotherapy ◽  
Acute Period ◽  
Intention To Treat ◽  
Grade 3 ◽  
To Receive

9633 Background: Combination of aprepitant, 5-HT3 receptor antagonist and steroid improve complete response (CR) of chemotherapy induced nausea and vomiting (CINV). But until now, there was no information whether ramosetron is as effective as other 5-HT3receptor antagonists for the combination regimen. Therefore, we compared a ramosetron, aprepitant and dexamethasone (RAD) with ondansetron, aprepitant and dexamethasone (OAD) to establish the non-inferiority of RAD in controlling highly emetogenic chemotherapy induced nausea and vomiting. Methods: A total of 334 patients with malignant disease who were scheduled to receive highly emetogenic chemotherapy were randomized to RAD or OAD. Aprepitant (125 mg day 1; 80 mg day 2, 3) and dexamethasone (12 mg day 1; 8 mg day 2-4) were administered to both group. Intravenous ramosetron (0.3mg day 1) or ondansetron (16mg day1) was given to RAD or OAD, respectively. Patients recorded vomiting and nausea (VAS score) on the diary. The primary end point was CR (no vomiting or retching and no rescue medication) rate in the acute period (chemotherapy day 1). The non-inferiority margin was defined as -15% differences. Results: 299 patients (RAD 143, OAD 156) were eligible for the efficacy analyses of modified intention-to-treat. Median age and sex were 60 (IQR 52 – 66) and 61 (51.5 – 68, p=0.54), 90 Male/66 Female and 114 Male/29 Female (p<0.0001) in RAD and OAD, respectively. There were no significant differences between two groups on the other baseline characteristics. The CR rates of RAD vs OAD were 84.6% vs 77.6% (95% C.I. -0.4 – 14.5%) at acute period, 69.5% vs 62.6% (-2.1 – 16.0%) at delayed period (days 2-5), and 66.7% vs 58.1% (-0.6 – 17.8%) at overall period. Median nausea score at acute period were 4 (IQR 2 – 5) and 3 (2-5, p=0.14) in RAD and OAD, respectively. There were no grade 3 or 4 toxicities. Conclusions: RAD regimen is as effective and tolerable as OAD antiemetic combination for the prevention of CINV in patients receiving highly emetogenic chemotherapy. Ramosetron could be considered as one of the best partners for aprepitant. Clinical trial information: NCT01536691.

scholarly journals The Efficacy, Safety, and Cost Benefit of Olanzapine versus Aprepitant in Highly Emetogenic Chemotherapy: A Pilot Study from South India

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Govind Babu ◽  
Smitha Carol Saldanha ◽  
Lakshmaiah Kuntegowdanahalli Chinnagiriyappa ◽  
Linu Abraham Jacob ◽  
Suresh Babu Mallekavu ◽  
...  
Keyword(s):  
Pilot Study ◽  
South India ◽  
Cost Benefit ◽  
Complete Response ◽  
Emetogenic Chemotherapy ◽  
Nausea And Vomiting ◽  
Highly Emetogenic Chemotherapy ◽  
Acute Period ◽  
Significant Difference ◽  
Grade 3

Background. The efficacy, safety, and cost benefit of olanzapine (OLN) when compared to aprepitant (APR) in the prevention of chemotherapy induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC) were evaluated. Methods. A prospective pilot study was done in chemotherapy-naive patients receiving HEC to compare OLN versus APR along with palonosetron and dexamethasone. 100 patients consented to the protocol and were randomized and evaluated for Complete Response (CR) (no emesis, no rescue). Results. CR was 86% for the acute period, 86% for the delayed period, and 80% for the overall period in 50 patients receiving the APD regimen. CR was 84% for the acute period, 88% for the delayed period, and 78% for the overall period for 50 patients receiving the OPD regimen. Patients without nausea were APD: 88% acute, 84% delayed, and 84% overall, and OPD: 84% acute, 88% delayed, and 84% overall. There were no significant grade 3 or 4 toxicities. OPD was comparable to APD in the control of CINV. Conclusion. In this study, there was no significant difference between olanzapine and aprepitant in preventing CINV with highly emetogenic chemotherapy. Olanzapine may thus be used as a potential, safe, and cost beneficial alternative to prevent nausea and vomiting in HEC.

scholarly journals TeleNeurological evaluation and Support for the Emergency Department (TeleNS-ED): protocol for an open-label clinical trial

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e048293
Author(s):  
Jessica Mandrioli ◽  
Mario Santangelo ◽  
Antonio Luciani ◽  
Stefano Toscani ◽  
Elisabetta Zucchi ◽  
...  
Keyword(s):  
Emergency Department ◽  
Clinical Investigation ◽  
Neurological Diseases ◽  
Medical Personnel ◽  
Primary Objective ◽  
Control Group ◽  
National Guidelines ◽  
Open Label ◽  
Time Saving ◽  
Hospital Networks

IntroductionThe COVID-19 pandemic compelled health systems to protect patients and medical personnel during transit in hospitals by minimising transfers, prompting the use of telehealth systems. In the field of neurology, telemedicine has been used in emergency settings for acute stroke management between spoke and hub hospital networks, where good outcomes have been achieved. However, data on the use of telemedicine in non-stroke acute neurological conditions accessing the emergency department (ED) are currently missing.Methods and analysesThis is an interventional, open-label trial on the use of teleconsultation in the ED for neurological diseases other than stroke. The study aims to develop a remote consultancy system (TeleNeurological Evaluation and Support, TeleNS) for patients with acute neurological symptoms referred to hospital facilities without a 24-hour availability of a neurologist consultant (spoke hospitals). The study population will include 100 ED patients referred to two spoke hospitals in 6 months, who will be asked to perform teleconsultation instead of inperson visits. As a control group, retrospectively available data from patients admitted to the ED of spoke hospitals during the same time period over the last 2 years will be evaluated. The primary objective is to assess whether a TeleNS for the ED guarantees a faster but qualitatively non-inferior diagnostic/therapeutic work-up if compared with inperson examination, assuring the availability of all the necessary examinations and treatments with consistent time-saving.Ethics and disseminationThe trial was designed following the national guidelines on clinical investigation on telemedicine provided by the Italian Ministry of Health and according to the Standard Protocol Items for Randomized Trials statement guidelines. This research protocol was approved by Comitato Etico Area Vasta Emilia Nord in September 2020 (number/identification: 942/2020/DISP/AOUMO SIRER ID 805) and was written without patient involvement. Patients’ associations will be involved in the dissemination of study design and results. The results of the study will be presented during scientific symposia or published in scientific journals.Trial registration numberNCT04611295.

scholarly journals A randomised, open label comparative study of hydroxychloroquine with betamethasone oral mini pulse in the management of patients with alopecia areata

2021 ◽  
Vol 10 (2) ◽  
pp. 187
Author(s):  
Jeyasudha Jambusayee ◽  
Kulur Mukhyaprana Sudha
Keyword(s):  
Alopecia Areata ◽  
Life Quality ◽  
Autoimmune Disorder ◽  
Study Groups ◽  
Pulse Therapy ◽  
The Body ◽  
Control Group ◽  
Study Group ◽  
Open Label ◽  
Significant Difference

Background: Alopecia areata is an autoimmune disorder causing patchy hair loss on scalp and other parts of the body and leading to poor self-esteem and anxiety in patients. Treatment with topical or systemic drugs like steroids or other immunosuppressants is associated with adverse effects. Hydroxychloroquine is an antimalarial drug, with T cell modulating function. This study was undertaken to assess the safety, efficacy and tolerability of Hydroxychloroquine in Alopecia areata compared to betamethasone oral mini pulse (OMP) therapy. Methods: 60 patients with alopecia areata were randomized into two groups of 30 each. Control group received tab. betamethasone 5 mg/day on two consecutive days of week for 12 weeks and Study group received tab. hydroxychloroquine 200 mg/day for 12 weeks. They were followed-up for further 12 weeks. Scale of alopecia tool, dermatology life quality index and global assessment at baseline, 12 weeks and 24 weeks were used to assess the outcome.Results: 94 patients were screened and 60 patients were included. All patients completed the study. At the end of 12 weeks, there was a statistically significant reduction in SALT and DLQI scores in both control and study groups. But at the end of 24 weeks, the study group showed an increase in the scores. Relapses were more in the study group. No significant difference in the incidence of adverse events was noted between the two groups.Conclusions: Hydroxychloroquine 200 mg/day is less efficacious in the management of alopecia areata in comparison to betamethasone oral mini pulse therapy.

A phase I trial evaluating NBTXR3 activated by radiotherapy in combination with nivolumab or pembrolizumab in patients with advanced cancers.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2590-2590
Author(s):  
Colette Shen ◽  
Jessica M. Frakes ◽  
Jiaxin Niu ◽  
Ari Rosenberg ◽  
Jared Weiss ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Trial ◽  
Tumor Regression ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Kidney Injury ◽  
Complete Response ◽  
Intratumoral Injection ◽  
Primary Objective ◽  
Open Label

2590 Background: Immune checkpoint inhibitors (ICIs) targeting PD-1 are an effective treatment for a variety of cancers. However, the majority of patients (pts) exhibit resistance to ICIs. Overcoming this resistance represents a major challenge in immuno-oncology. Emerging evidence suggests radiation therapy (RT) produces an immunomodulatory effect that may act synergistically with ICIs. However, RT dose and ultimate efficacy are limited by toxicity to surrounding healthy tissues. NBTXR3, a novel radioenhancer administered by direct intratumoral injection (ITI), is designed at the nanoscale to increase RT dose deposit within tumor cells and subsequent tumor cell killing, without increasing toxicity to surrounding healthy tissue. Preclinical data suggest NBTXR3/RT can trigger a local and systemic anti-tumor immune response and overcome anti-PD-1 resistance. NBTXR3/RT combined with anti-PD-1 may prime the immune system to increase the proportion of ICI responders, or convert ICI non-responders to responders. Methods: This is a multicenter, open-label, phase I trial [NCT03589339] to evaluate NBTXR3/RT/anti-PD-1 in 3 cohorts: (1) Locoregional recurrent or recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) amenable to HN re-irradiation, and metastases from any primary cancer eligible for anti-PD-1 (nivolumab or pembrolizumab) treatment specifically localized in the lung (2) or liver (3), respectively. Stereotactic body RT (SBRT) is delivered at tumor-site selective doses per standard practice. The primary objective is NBTXR3/RT/anti-PD-1 recommended phase 2 dose in each cohort. Secondary objectives are anti-tumor response (objective response rate), safety and feasibility of NBTXR3 injection. Results: Nine pts have been treated: 3 HNSCC, 4 lung, 2 liver. 7/9 pts were anti-PD-1 non-responders. Overall tumor regression was observed in 8/9 pts. NBTXR3/RT/anti-PD-1 resulted in tumor regression in 6/7 pts who had progressed on prior anti-PD-1. A complete response in the injected lymph node lasting over 1 year was observed in 1 anti-PD-1 naïve pt. 2 SAEs related to anti-PD-1 and possibly related to NBTXR3 (G5 pneumonitis, G4 hyperglycemia) were observed in 1 anti-PD-1 naïve HNSCC pt and considered DLTs. This pt also experienced 2 other SAEs related to anti-PD-1 (G4 diabetic ketoacidosis, G4 acute kidney injury). SBRT-related safety profile was as expected. Updated results will be presented. Conclusions: Data from this first-in-human phase I trial evaluating NBTXR3/RT/anti-PD-1 in pts with advanced cancers, show NBTXR3 ITI is feasible and well-tolerated. NBTXR3/RT/anti-PD-1 demonstrated promising signs of efficacy. Of particular interest, NBTXR3/RT can overcome ICI resistance in pts having progressed on prior anti-PD-1, supporting further development of NBTXR3 in combination with anti-PD-1 as well as other ICIs. Clinical trial information: NCT03589339.

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.

Vorinostat in combination with lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma: A phase I study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8586-8586
Author(s):  
D. S. Siegel ◽  
D. M. Weber ◽  
C. S. Mitsiades ◽  
M. A. Dimopoulos ◽  
J. L. Harousseau ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase I ◽  
Dose Escalation ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Open Label ◽  
Refractory Multiple Myeloma ◽  
Combination Methods ◽  
Novel Drug

8586 Background: Novel drug combinations may improve patient outcome in relapsed/refractory multiple myeloma (MM), which remains especially challenging to treat. Preclinical studies suggest that the histone deacetylase inhibitor vorinostat may have synergistic potential when combined with lenalidomide and dexamethasone. This phase I, multicenter, open-label study evaluated vorinostat plus lenalidomide and dexamethasone in patients (pts) with relapsed or refractory MM. The primary objective was to determine the maximum tolerated dose (MTD); other endpoints included overall safety and tolerability, as well as activity of the combination. Methods: Pts aged ≥18 years with relapsed or refractory MM were enrolled sequentially into 1 of 5 dosing levels ( Table ) using a standard 3+3 design for ≤8 cycles. Barring dose-limiting toxicities (DLTs) in the first cycle, dose escalation continued until the MTD was established. Response was assessed, and adverse events (AEs) were recorded. Results: Of 12 pts accrued to date, 11 (92%) have experienced ≥1 AE, with drug-related AEs reported by 6 pts (96% ≤Grade 2). The most common drug-related AEs (each in 4 pts) were fatigue and thrombocytopenia. Serious AEs in 2 pts (17%) were not considered drug-related. No pts discontinued due to AEs, and no DLT has been observed to date. Dose escalation to dose level (DL) 4 was achieved as no DLTs were observed in DLs 1–3. The MTD has not yet been reached. Of 11 pts evaluable for efficacy, best responses include: complete response in 1 pt, partial response in 2 pts, minimal response in 2 pts, and stable disease in 3 pts; 3 pts had progressive disease (PD). Currently, 9 pts remain on treatment, with 3 pts discontinuing treatment due to PD. Conclusions: These preliminary data suggest that vorinostat with lenalidomide and dexamethasone represents a well tolerated and active novel oral combination therapy for the treatment of relapsed/refractory MM. [Table: see text] [Table: see text]

Meta-analysis of trials comparing standard antiemetic treatment (SAT) with aprepitant containing antiemetic regimens (ACAR) for prevention of chemotherapy-induced nausea and vomiting (CINV).

2014 ◽  
Vol 32 (31_suppl) ◽  
pp. 171-171
Author(s):  
Neha Gupta ◽  
Hassan Hatoum ◽  
Omar Al Ustwani ◽  
Pongwut Danchaivijitr ◽  
Katy Wang ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Complete Response ◽  
Emetogenic Chemotherapy ◽  
Response To Treatment ◽  
Highly Emetogenic Chemotherapy ◽  
Antiemetic Treatment ◽  
Improved Outcomes ◽  
Score Method ◽  
American Society ◽  
Delayed Phase

171 Background: Various randomized controlled trials (RCTs) have shown improved outcomes with addition of aprepitant to standard antiemetic treatment (SAT) in preventing CINV. We conducted a meta-analysis to study the overall impact of ACAR in CINV prevention in adults. Methods: We searched Pubmed and Ovid databases, and American Society of Clinical Oncology meetings abstracts for RCTs using ACAR with SAT for CINV prevention in adult cancer patients (pts). Major study end points were complete response to treatment (CR; defined as no emesis and no use of rescue medications) in overall phase (OP; 0-120 hours of chemotherapy), acute phase (AP; 0-24 hours) and delayed phase (DP; 24-120 hours). Additionally, we assessed the control of nausea and toxicity profile (TP). Stouffer's Z-score method was used to calculate the overall effect. Results: 16 RCTs (5,547 pts) were included. 11 trials (3,314 pts) involved highly emetogenic chemotherapy (HEC) and 5 trials (2,233 pts) involved moderately emetogenic chemotherapy (MEC). ACAR increased CR in OP from 47% to 63% (OR=0.52, CI=0.46 to 0.58; p<0.001), in AP from 73% to 81% (p<0.01), and in DP from 51% to 66% (p<0.001). Significant increase in nausea control was seen in DP (p=0.03) but not in OP or AP. Incidence of various toxicities was statistically similar in both groups except slightly higher rate of fatigue (p=0.02) and hiccups (p<0.001), and lower rate of neutropenia (p=0.02) in ACAR. Conclusions: ACAR is effective in CINV due to both HEC and MEC in adult cancer pts. ACAR improves the control of emesis in all phases, and nausea in delayed phase only. With the exception of causing more fatigue & hiccups, and lesser neutropenia, overall TP of ACAR is similar to SAT.

Sign in / Sign up

Export Citation Format

Share Document