|Year : 2019 | Volume
| Issue : 1 | Page : 15-18
A retrospective case cohort analysis on the clinical utility of fosaprepitant in CINV prophylaxis in day care center of South India
Anita C Ramesh1, Sagar B Bhagat2
1 Department of Medical Oncology, HCG Cancer Centre, Chennai, Tamil Nadu, India
2 Department of Medical Affairs, Glenmark Pharmaceuticals Limited, Mumbai, Maharashtra, India
|Date of Web Publication||26-Jun-2019|
Dr. Sagar B Bhagat
Glenmark Pharmaceuticals Limited, Mumbai 400099, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Control of chemotherapy-induced nausea and vomiting is a crucial factor in ensuring patient’s compliance and adherence to cancer chemotherapy cycle. Fosaprepitant is a water-soluble N-phosphoryl derivative of aprepitant, which is often administered along with 5-hydroxytryptamine 3 antagonist and a steroid in patients with highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Materials and Methods: A single-centric, retrospective cohort study was conducted in HCG Cancer Centre in South India, where patients who were prescribed fosaprepitant as a part of standard therapy were enrolled. Results: Among the 290 patients who were included in the analysis, 41.72% were male, 58.27% were female, and 36.20% belonged to 51–60 years of age. Advanced breast carcinoma was the most common diagnosis in 38.96% patients. HEC was prescribed in 222 patients; moderate emetogenic drugs and regimen were prescribed in 62 patients. Among patients who were prescribed HEC and MEC drugs and regimen, fosaprepitant, palonosetron, and dexamethasone were prescribed on day 1 followed by dexamethasone on days 2, 3, and 4. No infusion site reaction, hiccups, or any other adverse reactions were noted. Complete response was noted in all patients (100%) with HEC and MEC regimen cases. The formulation was well tolerated with none reporting any persistent or delayed or breakthrough emesis. Conclusion: Single-dose fosaprepitant used in combination with palonosetron and dexamethasone was well tolerated and effective in preventing chemotherapy-induced vomiting in patients receiving highly and moderately emetogenic drugs and regimen.
Keywords: CINV, dexamethasone, fosaprepitant, palonosetron
|How to cite this article:|
Ramesh AC, Bhagat SB. A retrospective case cohort analysis on the clinical utility of fosaprepitant in CINV prophylaxis in day care center of South India. J Curr Oncol 2019;2:15-8
| Introduction|| |
Chemotherapy plays an important part in improving patient outcomes in patients with cancer and is a core stone of treatment for most patients with cancer. Despite the fact that chemotherapy plays an important role in the survival of patients, a high cost in terms of adverse effect and poor quality of life is related to it. Of the antagonistic impacts, none is more dreaded than chemotherapy-induced nausea and vomiting (CINV). It remains a critical clinical challenge because of significant negative effect of episodes of CINV such as dehydration, impairment of activity, and electrolyte imbalance. More serious outcomes of prolonged CINV include organ damage, esophageal tearing, and pneumonia from aspired vomit. Also being a further burden to patients’ well-being and quality of life, CINV can likewise disrupt and postpone chemotherapy schedules and even cause discontinuation of potentially beneficial chemotherapy., In addition, poor CINV control in the past cycles may bring about anticipatory CINV.
Prevention or easing of symptoms can limit these entanglements, enabling patients to continue with their cancer treatment. Medications utilized as a part of the prophylaxis and control of CINV include variety of antiemetic drugs such as serotonin receptor antagonists (e.g., ondansetron, palonosetron), corticosteroids (e.g., dexamethasone), and dopamine antagonists (e.g., metoclopramide). The orally administered NK1 receptor antagonist (NK1 RA) aprepitant is a relatively new expansion to the present scope of treatment choices and has, as of late, been reformulated as the intravenous preparation, fosaprepitant. Recent guidelines from the Multinational Association for Supportive Care in Cancer (MASCC) and European Society of Medical Oncology (ESMO), the American Society of Clinical Oncology (ASCO), and the National Comprehensive Cancer Network (NCCN) recommend the addition of an NK1 RA to the 5-hydroxytryptamine 3 (5-HT3) RA-corticosteroid combination, as the most effective regimen for controlling both acute and delayed CINV associated with highly emetogenic chemotherapy (HEC), or with anthracycline-cyclophosphamide (AC)–based regimens.
The combination of corticosteroid, serotonin antagonist, and aprepitant has been shown to have up to 90% efficacy in the prevention of both acute and delayed CINV. However, the current formulation of aprepitant for oral delivery, though highly effective, may not be ideal for every single clinical circumstance. Oral administration may not generally be plausible, for example, in patients who are not completely conscious or the individuals who cannot endure oral medications during an episode of nausea and vomiting. In fact, administration of a drug via the oral route may even cause or exacerbate symptoms and emesis shortly after receiving oral aprepitant, which could result in the loss of some or the whole of the dose. For patients on chemotherapy at high risk of oral mucositis, for example, those with head and neck malignancy, oral formulation may likewise be unsatisfactory. An alternative technique for administration would ease these issues.
As a reformulated prodrug, fosaprepitant evades the issues related with oral administration, and when implanted intravenously it is quickly converted to active aprepitant by phosphatase enzymes., Lasseter et al. demonstrated bioequivalence of fosaprepitant to aprepitant, and therefore the pharmacologic impacts of fosaprepitant are the same as, and directly attributable to, aprepitant.
Therefore, this study was conducted to assess the effect of single-dose fosaprepitant in enhancing compliance of patients to subsequent cycle while evading CINV in patients receiving HEC and moderately emetogenic chemotherapy (MEC).
| Materials and Methods|| |
This study was a single-centric retrospective cohort analysis, conducted in a tertiary care center of South India, where clinical data of patients who were prescribed fosaprepitant between October 2016 and March 2017 for CINV prophylaxis were gathered for analysis. After obtaining institutional ethics committee approval, data were recorded in a structured case record form, which was designed to capture demographic characteristics of patients such as age, gender, and other relevant information related to patient diagnosis, cancer stage, chemotherapy regimen with dose, and chemotherapy cycle. Antiemetic regimen given on the first and subsequent chemotherapy cycle was captured. Adverse effect related to antiemetic regimen, its efficacy in terms of vomiting/retching or rescue medication used, and response to the regime were also captured. Complete response was defined as no emetic episodes and no use of rescue medication for emesis. Confidentiality of the data was maintained throughout the study period. Data were compiled in Microsoft Office Excel version 2013 and a descriptive statistical analysis was carried out. Data are presented in the form of frequencies and percentages for qualitative variables, means, and standard deviations for quantitative variables.
| Results|| |
Consecutive patient record of 301 patients involving fosaprepitant was available; among whom, follow-up data of 11 patients were not available, thus 290 patients were incorporated into the analysis. Of the patients, 41.72% (121) were male and 58.27% (169) were female. Age-wise distribution of the patients showed that majority of the patients were above 50 years of age [Table 1]. Advanced breast carcinoma was the most common diagnosis (38.96% [n = 113]) among the study participants followed by lung carcinoma 10.68% (31) and ovary carcinoma 8.9% (26) [Table 2]. Stage-wise distribution of the study participants showed more than half of the participants (55.17%) were in stage III [Table 3]. HEC was prescribed in 222 patients (76.55%), MEC regimen was prescribed in 62 patients (21.37%), and 6 patients (2.06%) were prescribed low emetogenic chemotherapy (LEC) drugs [Table 4]. Doxorubicin/AC and taxane–paclitaxel were the common HEC regimens, whereas Rituximab–cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); folinic acid, 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI); and carboplatin–paclitaxel were the common MEC regimens prescribed. Among patients who were prescribed HEC (n = 222) and MEC (n = 62) drugs and regimen, fosaprepitant (150mg), palonosetron (0.25mg), and dexamethasone (16mg) were prescribed on day 1 followed by dexamethasone (8mg) on days 2, 3, and 4. No infusion site reaction, hiccups, or any other adverse reactions were noted. Complete response was noted in all patients (100%) with HEC and MEC regimen in acute, delayed, and overall phase [Figure 1]. The formulation was well tolerated with none reporting any persistent or delayed or breakthrough emesis. No rescue medications were used by study participants., , ,
|Table 4: Distribution of study participants according chemotherapeutic regimen prescribed|
Click here to view
| Discussion|| |
Nausea control has become the top priority of current antiemetic research to reach the last objective of no nausea/no vomiting after anticancer treatment. The poor control of nausea and vomiting in the acute phase turned out to be an important risk factor for the lack of control of these events in the delayed phase. Also, patients who were presented with delayed nausea and vomiting in the first cycle have a greater risk of presenting these symptoms in subsequent cycles. Therefore, good control of nausea and vomiting in the first cycle is important, keeping in mind the end goal to control them well in subsequent chemotherapy cycles. Current guidelines suggest that management of CINV should be based fundamentally on the emetogenic potential of the drugs selected for chemotherapy, which have been classified into four emetogenic risk groups: high, moderate, low, and minimal.
In our study, majority of the patients were prescribed HEC (76.55%) followed by MEC (21.37%). Most patients in HEC cohort received AC regimen (50.90%). In the MEC cohort, most patients (67.74%) received R-CHOP regimen. All those patients who received HEC (222) and MEC (62) were prescribed triple drug combination of fosaprepitant (150mg), palonosetron (0.25mg), and dexamethasone (16mg) on day 1 followed by dexamethasone (8mg) on days 2, 3, and 4. Role of triple drug combination of 5-HT3 RA, NK1 RA, and dexamethasone was well established in preventing CINV in patients who receive regimens with a high emetogenic potential, whereas in patients receiving MEC regimen, all the guidelines (ASCO, MASCC/ESMO, and NCCN) suggest the triple drug combination to be used only in patients who receive AC regimens. Rest all patients with non-AC-MEC can be managed with combination of 5-HT3 antagonist and dexamethasone. No rescue medication was used by study participants in our study.
Complete response was reported in all patients (100%) with HEC and MEC regimen cases in both acute and delayed phases. The results could be compared with study conducted by Weinstein et al. in patients who were prescribed MEC, where efficacy was 93.2% in acute phase, 78.9% in delayed phase, and 77.1% as overall control. Single-dose fosaprepitant was well tolerated in our study with none reporting any persistent or delayed or breakthrough emesis. Results of our study can be compared with Actual Data of Vomiting Incidence by Chemotherapy Evaluation (ADVICE) study conducted among patients who were prescribed MEC, where antiemetic regimen given was a combination of 5-HT3 antagonists + corticosteroid. ADVICE study reported vomiting in 20.8% and nausea in 42% patients. Complete response was 84.2% in the acute phase, 77% in the late phase, and 68.9% in overall period. Approximately, 31.1% patients did not achieve complete response and 17.9% required rescue medication in ADVICE study. Similar results have recently been published with regard to the Asian population in patients treated with HEC and MEC regimens whereas 318 patients were prescribed HEC and 330 MEC. After HEC, no emesis was recorded by 75% and no nausea by 38% of patients. After MEC, 80% had no emesis and 50% had no nausea. Complete response was recorded by 69%. For the acute and delayed phase after HEC, CINV prophylaxis preferred was the combination of 5-HT3-RA, corticosteroid, and NK1-RA. For the MEC acute phase and delayed phase, 5HT3-RA and a corticosteroid were preferred. NK1-RA was not used in acute phase and 4% in delayed phase for MEC.
Results of aforementioned studies thus highlight the importance of adding NK1 RA, such as fosaprepitant, in the management of CINV in patients on HEC and MEC regimen, especially in MEC regimen, where most of the studies have not preferred NK1 RA in the treatment regimen. Our study thus adds to the available evidence for fosaprepitant in AC-based MEC regimens, and suggests adding an NK1 RA in the overall MEC setting such as R-CHOP, FOLFOXIRI, paclitaxel + carboplatin, and daunorubicin + cytarabin 100–200mg/m2.
| Conclusion|| |
Single-dose fosaprepitant used in combination with palonosetron and dexamethasone was well tolerated and effective in preventing CINV in patients receiving highly and moderately emetogenic regimen. Our findings clearly demonstrate the advantage of adding fosaprepitant for the prevention of CINV in a well-defined MEC population.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Hawkins R, Grunberg S. Chemotherapy-induced nausea and vomiting: Challenges and opportunities for improved patient outcomes. Clin J Oncol Nurs 2009;13:54-64.
Bender CM, McDaniel RW, Murphy-Ende K, Pickett M, Rittenberg CN, Rogers MP, et al
. Chemotherapy-induced nausea and vomiting. Clin J Oncol Nurs 2002;6:94-102.
Bošnjak SM, Gralla RJ, Schwartzberg L. Prevention of chemotherapy-induced nausea: The role of neurokinin-1 (NK1) receptor antagonists. Support Care Cancer 2017;25:1661-71.
Multinational Association for Supportive Care in Cancer: MASCC/ESMO antiemetic guidelines. Available from: http://www.mascc.org/antiemetic-guidelines. Updated 2013. [Last accessed on 2018 Dec 19].
Basch E, Prestrud AA, Hesketh PJ, Kris MG, Feyer PC, Somerfield MR, et al
. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. [published correction appears in J Clin Oncol 2014;32:2117]. J Clin Oncol 2011;29:4189-98.
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Antiemesis. Version 1.2014. Available from: http://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf. [Last accessed on 2018 Dec 10].
Langford P, Chrisp P. Fosaprepitant and aprepitant: An update of the evidence for their place in the prevention of chemotherapy-induced nausea and vomiting. Core Evid 2010;5:77-90.
Huskey SE, Luffer-Atlas D, Dean BJ, McGowan EM, Feeney WP, Chiu SH. Substance P receptor antagonist I: Conversion of phosphoramidate prodrug after i.v. administration to rats and dogs. Drug Metab Dispos 1999;27:1367-73.
Hale JJ, Mills SG, MacCoss M, Dorn CP, Finke PE, Budhu RJ, et al
. Phosphorylated morpholine acetal human neurokinin-1 receptor antagonists as water-soluble prodrugs. J Med Chem 2000;43:1234-41.
Lasseter KC, Gambale J, Jin B, Bergman A, Constanzer M, Dru J, et al
. Tolerability of fosaprepitant and bioequivalency to aprepitant in healthy subjects. J Clin Pharmacol 2007;47:834-40.
National Comprehensive Cancer Network. NCCN practice guidelines in oncology: Antiemesis v2 2014. Available from: www.nccn.org. [Last accessed on 2017 Dec 14].
Kris MG, Hesketh PJ, Somerfield MR, Feyer P, Clark-Snow R, Koeller JM, et al
; American Society of Clinical Oncology. American Society of Clinical Oncology guideline for antiemetics in oncology: Update 2006. J Clin Oncol 2006;24:2932-47.
Jordan K, Gralla R, Jahn F, Molassiotis A. International antiemetic guidelines on chemotherapy induced nausea and vomiting (CINV): Content and implementation in daily routine practice. Eur J Pharmacol 2014;722:197-202.
Weinstein C, Jordan K, Green SA, Camacho E, Khanani S, Beckford-Brathwaite E, et al
. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: Results of a randomized, double-blind phase III trial. Ann Oncol 2016;27:172-8.
Escobar Y, Cajaraville G, Virizuela JA, Álvarez R, Muñoz A, Olariaga O, et al
. Incidence of chemotherapy-induced nausea and vomiting with moderately emetogenic chemotherapy: ADVICE (Actual Data of Vomiting Incidence by Chemotherapy Evaluation) study. Support Care Cancer 2015;23:2833-40.
Hsieh RK, Chan A, Kim HK, Yu S, Kim JG, Lee MA, et al
. Baseline patient characteristics, incidence of CINV, and physician perception of CINV incidence following moderately and highly emetogenic chemotherapy in Asia Pacific countries. Support Care Cancer 2015;23:263-72.
[Table 1], [Table 2], [Table 3], [Table 4]