Evaluation of pre-chemotherapy antiemetic prescriptions in a hospital unit

Introduction: Antineoplastic drugs, due to their high toxicity, can lead to adverse reactions to drugs, such as emesis, which causes discomfort to the patient. These drugs can be classified according to emetogenic potential and have appropriate treatment protocols. Objectives: The aim of this study is to evaluate whether there is compliance between antiemetic prescription in patients receiving antineoplastic treatment in a hospital unit, according to pre-established emesis prevention protocols. Methods: This is a cross-sectional retrospective study of chemotherapy prescriptions analysis from January to April 2017. Data were analyzed according to the National Comprehensive Cancer Network 2017 Acute Emesis Prevention Protocol. Nonconformities were classified in: wrong medicine; wrong dose; wrong administration frequency and wrong administration route. Results: Of the 919 prescriptions analyzed, 83% did not comply with the protocol. The most common nonconformity found in the study was the wrong dose with the most prevalent scenario being the dexamethasone dose above the required dose. Conclusion: Most of the prescriptions analyzed did not comply with the pre-established protocol. This increases the likelihood of adverse drug reactions, does not effectively prevent emesis, thereby increasing patient weakness, decreasing quality of life, and wasting resources.

Short-course olanzapine to prevent delayed emesis following carboplatin/paclitaxel for gynecologic cancer: a randomised study

Purpose: To explore efficacy of short-course olanzapine with or without low-dose dexamethasone for prevention of delayed emesis in gynecologic cancer patients receiving carboplatin/paclitaxel. Methods: This was a prospective study in 81 chemo-naive patients receiving 0.25 mg intravenous palonosetron, 16 mg dexamethasone, and 10 mg oral olanzapine before chemotherapy. On days 2 and 3, patients randomly received 10 mg olanzapine (arm A; n=27), 10 mg olanzapine plus 4 mg dexamethasone (arm B; n=27), or 8 mg dexamethasone (reference arm C; n=27). The primary endpoint was total control (TC; no vomiting, no rescue antiemetics, and no nausea) on days 2–5, using a diary. Secondary endpoints included proportion of patients with no emesis impact on daily life using the Functional Living Index–Emesis (FLIE) questionnaire, and patient’s satisfaction with antiemetic coverage. Results: Fifty-two percent of patients in arm A ( P=0.406), 59% in arm B ( P=0.779), and 67% in arm C had a delayed TC. Secondary analyses showed no significant difference across arms in any efficacy endpoint. FLIE scores as well as mean satisfaction scores were similar across arms. Conclusions: In this exploratory study with a small sample size, we did not find any clue about better control of delayed emesis with either olanzapine regimen in gynecologic cancer patients treated with carboplatin/paclitaxel and receiving the same prophylaxis for acute emesis.

A retrospective study of a dexamethasone-sparing strategy of preventing acute and delayed emesis caused by CapeOx regimen with aprepitant for colorectal cancer.

632 Background: CapeOx therapy which is combination with oxaliplatin (L-OHP) and capecitabine is one of the standard treatments for first line chemotherapy for unresectable colorectal cancer, or for postoperative adjuvant chemotherapy for stage III colon cancer. L-OHP-based regimen is classified as moderately emetogenic chemotherapy. In the SENRI trial which we previously conducted as phase III trial, aprepitant, an NK-1 antagonist, showed the efficacy for prevention of emesis against L-OHP. On the other hand, even when in highly emetogenic chemotherapy, it is reported that dexamethasone after day 2 could be spared. Methods: We retrospectively reviewed chemo-naive 94 patients with colorectal cancer who underwent CapeOx therapy at our institution from April 2012 to March 2017. We assessed the relationship between emesis during the first cycle of CapeOx (day1-5) and the use of dexamethasone on day 2-3. Results: 10 patients underwent CapeOx plus bevacizumab, and 84 underwent CapeOx. All patients received 5-HT3 receptor antagonist (palonosetron: 87, granisetron: 7). 50 patients received aprepitant on days 1-3 and dexamethasone on day 1 (APR+D1 group). 22 patients received aprepitant on days 1-3 and dexamethasone on days 1-3 (APR+D3 group). 15 were dexamethasone on days 1-3 without aprepitant (D3 group), and 7 were dexamethasone only on day 1 without aprepitant (D1 group). Acute complete response (CR; no vomiting and no rescue anti-emetics) rates were 100% in any groups. Delayed CR rate was 56% in APR+D1 group, 86% in APR+D3 group, 53% in D3 group, and 29% in D1 group, respectively. In multivariate linear regression with aprepitant, there was a significant difference in presence of dexamethasone (p = 0.028). Conclusions: Acute emesis could be prevented by even only 1-day administration of dexamethasone when combined with the triplet prophylactics. However, in order to sufficiently prevent delayed emesis induced by L-OHP, it was suggested that addition of DEX on days 2 and 3 might be better.

A retrospective review of treatment patterns of antiemetic agents for chemotherapy-induced nausea and vomiting

Objectives: To evaluate the treatment pattern of antiemetic agents used for chemotherapy-induced nausea and vomiting in a tertiary hospital in Saudi Arabia. Methods: Over a period of 7 weeks, all new chemotherapy order sheets were collected and evaluated for chemotherapy-induced nausea and vomiting management. We compared each antiemetic regimen used for chemotherapy-induced nausea and vomiting prophylaxis with three international antiemetic guidelines by the following organizations: the Multinational Association of Supportive Care in Cancer, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network for the clinician. Results: A total of 152 cancer patients were included in the study, for whom 289 chemotherapy physician orders included antiemetic regimens. Approximately 17.3% of the chemotherapy protocols had total minimal emetogenicity risk, 22.5% had low risk, 37.02% had moderate risk, and 23.18% had high risk. For acute emesis, 27.57% of the antiemetic regimens followed at least one of the three reference guidelines. For delayed emesis, only 20.16% of the antiemetic regimens adhered to at least one of the three reference guidelines. Conclusion: Adherence to treatment recommendations and antiemetics prescribing for chemotherapy-induced nausea and vomiting was suboptimal at this hospital. However, institutional antiemetic guidelines and oncology pharmacists could play an important role in better assessment and management of chemotherapy-induced nausea and vomiting.

Effectiveness of antiemetics in control of antineoplastic chemotherapy-induced emesis at home

Objective Evaluating if antiemetics are effective in the prevention or treatment at home, of chemotherapy-induced emesis. Methods In total, were included 42 women with breast cancer in moderately emetogenic chemotherapy, using dexamethasone/ondansetron before each cycle. The frequency of nausea and vomiting was obtained by applying the instrument in the pre-chemotherapy period, and 24h, 48h, 72h and 96h after chemotherapy. The use of antiemetics was considered in accordance with adherence to medical prescription. Results All patients (n = 42, 100%) reported emesis at some point. Only five cases (11.9%) were anticipatory. In the first 24 hours (acute emesis), 38 (90.5%)ayed), emesis was reported by all despite the regular use (n = 20, 47.6%) or not (n = 22, 52.4%) of antiemetics (ondansetron, dexamethasone and metoclopramide/or dimenhydrinate). Conclusion Antiemetics were not effective in the prevention or treatment at home, of chemotherapy-induced emesis.

Aprepitant Versus Dexamethasone for Preventing Chemotherapy-Induced Delayed Emesis in Patients With Breast Cancer: A Randomized Double-Blind Study

PurposeA combination of aprepitant, a 5-HT3 receptor antagonist, and dexamethasone is recommended for the prophylaxis of acute or delayed emesis induced by chemotherapy containing anthracyclines plus cyclophosphamide in patients with breast cancer. The aim of this study was to verify whether dexamethasone is superior to aprepitant in preventing delayed emesis in patients receiving the same prophylaxis for acute emesis.Patients and MethodsA randomized double-blind study comparing aprepitant versus dexamethasone was completed in chemotherapy-naive patients with breast cancer treated with anthracyclines plus cyclophosphamide. Before chemotherapy, all patients were treated with intravenous palonosetron 0.25 mg, dexamethasone 8 mg, and oral aprepitant 125 mg. On days 2 and 3, patients randomly received oral dexamethasone 4 mg twice per day or aprepitant 80 mg once per day. Primary end point was rate of complete response (ie, no vomiting or rescue treatment) from days 2 to 5 after chemotherapy.ResultsOf 580 enrolled patients, 551 were evaluable: 273 received dexamethasone, and 278 received aprepitant. Day 1 complete response rates were similar: 87.6% for dexamethasone and 84.9% for aprepitant (P < .39). From days 2 to 5, complete response rates were the same with both antiemetic prophylaxes (79.5%; P < 1.00), as were results of secondary end points (ie, complete protection, total control, no vomiting, no nausea, score of Functional Living Index–Emesis; P < .24). Incidences of insomnia (2.9% v 0.4%; P < .02) and heartburn (8.1% v 3.6%; P < .03) were significantly greater with dexamethasone on days 2 to 5.ConclusionIn patients with breast cancer treated with anthracycline plus cyclophosphamide chemotherapy and receiving the same antiemetic prophylaxis for acute emesis, dexamethasone was not superior to aprepitant but instead had similar efficacy and toxicity in preventing delayed emesis.

Aprepitant (AP) versus dexamethasone (D) for preventing delayed emesis induced by anthracyclines plus cyclophosphamide (A+C) chemotherapy (CT) in breast cancer patients (pts): A double-blind, multicenter, randomized study.

9614 Background: A combination of AP + a 5-HT3 receptor antagonist + D and AP alone is recommended, respectively, for the prophylaxis of acute and delayed emesis induced by A+C CT in breast cancer pts. In the registrative study the role of AP in delayed emesis was not defined because prophylaxis of acute emesis was different between the two arms, and the superiority of AP on delayed emesis could be the consequence of a dependent effect on the different results achieved in acute phase. Aim of this study was to compare the efficacy of AP versus D in preventing delayed emesis in pts receiving the same prophylaxis of acute emesis. Methods: A randomized double-blind study comparing AP versus D was completed in naive breast cancer pts treated with A+C. Before CT, all pts were treated with intravenous palonosetron 0.25 mg and D 8 mg, and oral AP 125 mg. On days 2 and 3 pts randomly received D 4 mg bid or AP 80 mg qd. Primary endpoint was rate of complete response (no vomiting, no rescue treatment) from days 2 - 5 after CT. Results: From September 2009 to July 2012, 580 pts were enrolled; 551 were fully evaluated, 273 in arm D and 278 in arm AP. Day 1 complete response rates were similar: 239/273 (87.6%) in D arm and 236/278 (84.9%) in AP arm. From day 2-5, complete response was the same with both antiemetic prophylaxes (79.5%), and all secondary endpoints (complete protection, total control, no vomiting, no nausea, score of FLIE) assumed similar values. During the delayed phase, incidence of insomnia (2.9% vs. 0.4%) and heartburn (8.1% vs. 3.6%) was significantly superior in D arm. Conclusions: In breast cancer pts submitted to A+C CT and receiving the same antiemetic prophylaxis for acute emesis, D and AP present similar efficacy and toxicity. Clinical trial information: NCT 00869973.

Effects of Aprepitant on Drug Metabolism in Lymphoma Patients Receiving Multi-Day Chemotherapy Regimen of Cyclophosphamide, Doxorubicin, Vincristine, Prednisone, + Rituxan (R/CHOP): Randomized, Cross-Over Study

Abstract 1613 Chemotherapy-induced nausea and vomiting (CINV) is a frequent adverse event that can impair the quality of life in cancer patients (pts). In pts receiving cyclophosphamide (CP) and doxorubicin-based regimen, the combination of dexamethasone (dexa) and 5-HT3 receptor antagonists (5-HT3 RA) is very effective in acute emesis, however, control of delayed-emesis remains poor. The neurotransmitter substance P appears to be involved in both the acute and delayed-phases. Aprepitant, a substance P/ neurokinin (NK)-1 receptor antagonist, when combined with 5-HT3 RA and dexa, has been shown to prevent acute and delayed CINV associated with moderately and highly emetogenic chemotherapy (CT). However, aprepitant is a moderate inhibitor of cytochrome p-450 system, primarily via CYP 3A4, a liver microsome that also metabolizes several CT agents, including CP to some extent, its use has been approached with caution. This study evaluated the effect of aprepitant on drug metabolism in lymphoma pts receiving (R)CHOP which contains several agents that can be affected by this pathway. This randomized, cross-over trial was designed to enroll 18 evaluable pts; the absence of pharmacokinetic (PK) drug interactions can be determined if the 90% confidence interval (CI) of the geometric mean AUC ratio between 2 groups is within 80 to 125%. All pts received standard anti-emetic regimen of 5-HT3 RA (ondansetron) and steroids. The pts were randomized into 2 groups. Group 1 received aprepitant in cycle-1 and not in cycle-2. Group 2 received aprepitant in cycle-2 and not in cycle-1. The cross-over design was used to minimize inter-patient PK variability and drug cumulative effects, by using the patients as their own control. For breakthrough N/V, medications that are substrates, inducers, or inhibitors of CYP 3A4 were not permitted. Blood samples were drawn during and post CT infusion in both groups at following time points: baseline before the start of treatment, 30, 60, 75, and 90 minutes, and 2, 4, 6, 8, and 24 hours from the start of CP infusion. Samples were analyzed for concentration of CP, vincristine, and prednisone, and their active metabolites. Eighteen of the 23 pts enrolled completed 2 cycles and were evaluable for PK analysis. Both groups were comparable with regards to demographics. The data for AUC for parent drug and metabolites are shown below.Geometric Mean AUC 0–24hr [(μg/mL*hr)/mL]Ratio of Geometric Mean AUC 0–24hr Analyte in Aprepitant Treatment to Control (90% CI)AprepitantControl1.20 (1.08–1.33)CP300.0250.52-deCl-CP4.560.75 (0.65–0.86)4-OH-CP3.940.97 (0.83–1.13)PR€2872651.08 (1.02–1.15)PL€441638171.16 (1.01–1.32)VC€41391.04 (0.82–1.33)€(ng/mL*hr) Abbreviations: CP, Cyclophosphamide; 2-deCl-CP, 2-dechloro-cyclophosphamide; 4-OH-CP, 4-hydroxy-cyclophosphamde, PR; prednisone, PL; prednisolone, VC; vincristine The AUC for active metabolite (4-OH-CP) was within the pre-defined range; but there was some increase in the parent CP and some decrease in the toxic metabolite (2-deCl-CP). The AUC for PR was within the defined range. Although, there was some increase in the active metabolite PL, the blood sugar levels were not significantly different in 2 groups (mean change 43% vs 37%). The Functional Living Index-Emesis (FLIE) scores for N/V were not significantly different. There were no serious adverse events related to aprepitant. Conclusions: Administration of aprepitant with (R)CHOP resulted in minor changes in the levels of parent drugs and/or metabolites; which are unlikely to have significant clinical impact. Disclosures: Vadhan-Raj: Merck: Research Funding. Spasojevic:Merck: Research Funding. Neelapu:celgene: Research Funding.