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Supplements Managed Care Considerations in Chemotherapy-Induced Nausea and Vomiting
Overview of Chemotherapy-Induced Nausea and Vomiting and Evidence-Based Therapies
Nelly Adel, PharmD, BCOP, BCPS
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Chemotherapy-Induced Nausea and Vomiting: Roles of Pharmacists and Formulary Decision Makers
Stacey W. McCullough, PharmD
Managed Care Considerations in Chemotherapy-Induced Nausea and Vomiting

Chemotherapy-Induced Nausea and Vomiting: Roles of Pharmacists and Formulary Decision Makers

Stacey W. McCullough, PharmD
Despite guidelines and medications available for the management of chemotherapy-induced nausea and vomiting (CINV), many patients with cancer are persistently affected by this dreadful adverse effect. It is not only physically and mentally draining, but financially strenuous as well. Along with these concerns, health-related consequences as dehydration, epigastric pain, and anorexia can arise. Therefore, compliance becomes a big issue in this patient population. It is important for healthcare professionals to educate patients and incorporate strategies by not only addressing but also individualizing treatment regimens and determining risk factors for potential CINV. By making formulary considerations using patient-centered and evidence-based treatment, patient outcomes can improve. Overall, it is necessary to understand the impact of CINV on quality of life and addressing it actively can significantly enhance care of patients with cancer.

Am J Manag Care. 2017;23:-S0
Chemotherapy-induced nausea and vomiting (CINV) is among the most common and distressing adverse events (AEs) associated with chemotherapy.1,2 Despite advances in chemotherapy and the provision of expert guidelines in managing CINV, 80% of patients undergoing chemotherapy continue to experience CINV.3-5 The effect of CINV on patients is physically, mentally, and financially burdensome, resulting in increased direct and indirect costs and decreased health-related quality of life (HRQOL).6-11 While nausea and vomiting, and the resulting effects, are the main influencers of HRQOL, drivers of the financial burden of CINV include direct costs resulting from inadequate prophylaxis, indirect costs from diminished HRQOL, and the cost of noncompliance with cancer therapy such as disease progression due to CINV.

Understanding CINV
CINV can be categorized as acute, delayed, anticipatory, breakthrough, or refractory. 12,13 The initial incidence of CINV is predictive for CINV in subsequent cycles, and a lack of control of CINV in the acute phase is often predictive of an inability to control delayed CINV.14 However, delayed CINV can occur in patients who do not experience acute CINV.14 Factors affecting CINV include a history of nausea and vomiting (eg, motion sickness), age, sex, alcohol consumption, type and dosage of chemotherapeutic agent, administration route, and/or schedule.13 Studies have shown delayed CINV is more common than acute CINV and tends to occur in patients receiving carboplatin, cisplatin, cyclophosphamide, or doxorubicin.6,13,15,16

Chemotherapeutic agents have been classified according to the associated risk of inducing acute nausea and vomiting as high–emetic risk chemotherapeutic (HEC) agents, moderate–emetic risk chemotherapeutic (MEC) agents, and low–emetic risk (LER) chemotherapeutic agents. HEC agents, including cisplatin, dacarbazine, and high-dose cyclophosphamide (≥1500 mg/m2), cause CINV in >90% of patients.13,17 MEC agents, including carboplatin, cyclophosphamide <1500 mg/m2, anthracyclines, and oxaliplatin, cause CINV in 30% to 90% of patients.13,17,18 LER agents, including etoposide, methotrexate, taxanes, gemcitabine, pemetrexed, lenalidomide, and temsirolimus, are associated with CINV in 10% to 30% of patients. Fewer than 10% of patients experience CINV after receiving minimal emetic risk agents, including bleomycin, bevacizumab, vincristine, epidermal growth factor receptor inhibitors, and fludarabine.13,18

In a study evaluating 240 chemotherapy-naïve patients receiving MEC between April 2012 and May 2013, physicians estimated prophylaxis would be effective for 75% .16 However, despite receiving prophylactic treatment, 31% of patients did not achieve a complete response and 38% complete protection. Although nausea was better controlled than vomiting, late-phase response was not as well controlled as acute-phase response. In general, it was concluded that healthcare professionals overestimated the effectiveness of antiemetic prophylaxis; 56% of patients in the study were not even administered antiemetic medication for delayed-onset CINV.16

According to the National Comprehensive Cancer Network (NCCN) guidelines, the goal of emesis control is to prevent nausea and/or vomiting throughout the entire period of risk, which lasts for at least 3 days for HEC and 2 days for MEC after the last dose of chemotherapy.13 Effective treatment of delayed-onset CINV continues to be a significant problem in patients who receive chemotherapy, despite treatment guidelines.16

Consequences of CINV
Inappropriate treatment of nausea has a significant impact on HRQOL and may be a prognostic factor for overall survival.6,19-21 CINV can increase the risk of electrolyte imbalance, dehydration, epigastric pain, and other gastrointestinal complications. These can lead to rehospitalization, the need for hydration therapy, and reduced HRQOL, resulting in reduced participation in activities of daily living as well as health-related costs. 6,7 Uncontrolled CINV is also associated with noncompliance with anticancer therapy, which may further affect patient outcomes.1,10

Quality-of-Life Considerations
CINV can result in metabolic imbalances, degeneration of self-care and functional ability, nutrient depletion, and anorexia.13 The Functional Living Index-Emesis (FLIE) is a validated 7-point visual analog scale tool that includes 9 questions related to the effects of nausea and vomiting on activities of daily living as well as social and emotional functioning for up to 5 days after chemotherapy.22,23 It is one of many validated nausea- and vomiting-specific assessment tools used to measure the impact of CINV on HRQOL and daily living based on patient-reported outcome measures.

The Anti-Nausea Chemotherapy Registry (ANCHOR) study assessed the impact of acute and delayed nausea and vomiting after HEC and MEC on patients’ quality of life (QOL) using FLIE.6 Of the 298 patients in the study (67 patients on HEC, 231 patients on MEC), 59.7% reported experiencing nausea (36.2% acute, 54.3% delayed) and 36.4% reported vomiting (13.2% acute, 32.5% delayed). As expected, patients on HEC reported significantly lower mean FLIE total scores than patients on MEC (95.5 vs 107.8, respectively; P = .0049). Although 173 patients did not report either nausea or vomiting during the first 24 hours after chemotherapy, 22.9% reported an impact on daily life caused by delayed CINV.6 The ANCHOR study demonstrated that CINV adversely affects patient QOL, even after treatment with MEC regimens and in those who do not experience nausea and vomiting during the first 24 hours after chemotherapy.6

In another study of 178 patients undergoing chemotherapy, 61.2% reported experiencing CINV: 34.3% had acute CINV and 58.4% had delayed CINV.7 On average, patients reported CINV 1.76 days following chemotherapy. Reduced daily functioning due to CINV was reported in 37.2% of all patients, and of those with poorly managed CINV, about 90% reported FLIE scores indicating a significant impact on daily functioning.7 Conversely, of the patients with well-managed CINV who did not experience vomiting or did not need rescue medication (complete responders), 90% had an average FLIE score indicating no impact on daily living (NIDL). Only 36% of noncomplete responders had FLIE scores indicating NIDL.7 As such, QOL monitoring is important as part of comprehensive patient management that can result in improved changes in antiemesis treatment and potentially improved QOL outcomes.

Studies have demonstrated that QOL scales may be independent prognostic factors of overall survival in patients with cancer.19-21 One reanalysis of the impact of QOL in patients with hepatocellular carcinoma (HCC) found that better role functioning (HR, 0.991; 95% CI, 0.987-0.995) was associated with longer survival.20 This association was confirmed in another study of 489 patients with HCC using the Spitzer QOL index.19 A meta-analysis of 30 randomized controlled trials with survival data for 10,108 patients with 11 cancer sites found that HRQOL parameters of physical functioning (HR, 0.94; 95% CI, 0.92-0.96; P <.0001), pain (HR, 1.04; 95% CI, 1.02-1.06; P <.0001), and appetite loss (HR, 1.05; 95% CI, 1.03-1.06; P <.0001) provided significant prognostic information and could help predict survival in patients with cancer.21

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