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www.TheOncologyPharmacist.com ogy practice for rescue medication within 2 to 5 days postchemotherapy; unscheduled hydration or office visits due to CINV; phone calls complaining of symptoms; or documented switching of outpatient antiemetics on days 2 to 5 after chemotherapy.9 Challenges in the treatment of CINV Investigators have identified several barriers to optimal CINV control, including the underestimation of CINV
may not remember to bring their prescribed oral therapies on the scheduled day of chemotherapy. It is important for providers to have the ability to administer IV antiemetics in such situations.12 Coverage and clinical decisions should support the antiemetic formulation that most effectively prevents CINV at the outset, thereby potentially reducing delayed adverse outcomes and associated costs. In this respect, clinicians play an important role in address-
Coverage decisions that limit the discretion of healthcare providers to prescribe specific formulations of antiemetics present other challenges. by clinicians and the underreporting of symptoms by patients. According to results of a study by Grunberg and colleagues, more than 75% of physicians and nurses underestimated the incidence of delayed CINV following HEC and MEC, although they accurately predicted the incidence of acute CINV.4 The discrepancy between the perceived and actual incidence of CINV may be partly explained by the fact that patients are often at home when they experience delayed nausea and vomiting and may not report these symptoms. Underutilization of and noncompliance with practice guidelines are further barriers to optimal control of CINV.10 These guidelines are designed to help physicians deliver high-quality care; however, this goal can only be achieved through adherence to their recommendations.10 In particular, there is a marked need to implement more effective strategies for the management of delayed CINV. The prevention of CINV in patients receiving multiday chemotherapy also remains challenging, since these individuals are at risk for both acute and delayed CINV, based on the emetogenic risk and sequence of agents.1,11 Coverage decisions that limit the discretion of healthcare providers to prescribe specific formulations of antiemetics present other challenges.12 Studies have shown that, in general, oral antiemetic formulations are equivalent to intravenous (IV) formulations.1 With evidence to support the bioequivalence of one antiemetic formulation with another, the argument could be made that withholding the IV formulation until the patient has demonstrated failure on the oral formulation would appear to be costeffective and prudent. However, this strategy may result in unintended adverse consequences. For example, consistent adherence to oral antiemetic regimens may be challenging for patients who may already be taking several other medications. In addition, most private-practice and hospital-based providers do not dispense oral medications, and patients
ing policy, cost, and reimbursement issues that may limit a patientâ€™s access to optimal antiemetic therapies. Goals and strategies for effective CINV control Before deciding on an antiemetic strategy, clinicians must consider the type of CINV being targeted, individual patient risk factors, and the specific chemotherapeutic agents being administered. There are five classifications of CINV, as shown in Table 1.1 Addressing the specific variables and concerns related to each classification is essential for reducing morbidity and increasing the likelihood that patients will be able to complete chemotherapy. Several patient factors may influence the occurrence and severity of CINV.1,13,14 In general, patients who are female, younger than 50 years of age, and on HEC regimens are at greater risk for developing CINV, as are individuals who have previously experienced episodes of nausea and vomiting. Other risk factors include high tumor burden, history of motion sickness, opioid use for pain management, and alcohol use in patients who
Antiemetic treatment should be initiated before chemotherapy begins in order to provide maximum protection against symptoms.
are unaccustomed or sensitive to alcohol. Conversely, patients with a history of chronic alcoholism have a decreased risk of emesis.1,14 Clinicians must also consider potential nonchemotherapy-related causes of emesis, including bowel obstruction, vestibular dysfunction, electrolyte imbalance, brain metastasis, concomitant drugs, uremia, anxiety, or other factors.1
It is essential to know the emetogenic risk level of the chemotherapy agents being used.1 These levels are defined as: high risk (>90%), moderate risk (30%90%), low risk (10%-30%), and minimal risk (<10%) (Table 2). When selecting an antiemetic therapy, the emetogenicity of a chemotherapeutic agent or combination should be the dominant consideration.2 The toxicity of the antiemetic agents and potential drugâ€“drug interactions should also be considered.2,15 Antiemetic treatment should be initiated before chemotherapy begins in order to provide maximum protection against symptoms and avoid CINV-related complications.1 Antiemetic agents exert their effects differently during the course of emesis and work synergistically with other antiemetics.1 Because these agents inhibit different pathways and a final common pathway has not yet been identified, no single antiemetic agent can be expected to provide complete protection throughout the different phases of emesis associated with chemotherapy.1 Antiemetic regimens should protect patients throughout the full period of anticipated CINV; the risk of CINV is at least 3 days for HEC and 2 days for MEC after the last dose of chemotherapy.1 For multidrug chemotherapy regimens, antiemetic therapy should be selected according to the agent with the highest emetogenic risk.1 The potential for anticipatory CINV in patients who have a poor initial experience with CINV increases the likelihood of symptoms with subsequent chemotherapy cycles. Thus, it is important to achieve optimal care with the first cycle of treatment.12 Optimizing control of CINV also requires that clinicians are aware of the most recent practice guidelines, and are willing to integrate these recommendations into everyday clinical practice. Adherence to the guidelines should be accompanied by accurate assessment of CINV symptoms through appropriate tools and better communication with patients after they leave the clinic. Advances in the treatment of CINV Over the past several decades, dramatic progress has been made in the supportive care of patients receiving chemotherapy. This is due largely to the introduction of more effective and better-tolerated antiemetic therapies. To date, serotonin subtype-3 receptor antagonists (5-HT3 RAs) and neurokinin-1 receptor antagonists (NK-1 RAs) appear to be among the most effective agents.2 Serotonin receptor antagonists The development of 5-HT3 RAs has marked a significant advancement in the treatment of CINV, and clinical data support the effectiveness of these agents.1 The 5-HT3 RAs that represent
Table 1 Classifications of CINV Acute CINV Occurs within minutes to several hours after drug administration. Usually resolves within the first 24 hours. Intensity generally peaks after 5 to 6 hours. Delayed CINV Develops in patients >24 hours after administration of chemotherapy. Occurs commonly after administration of cisplatin,a carboplatin, cyclophosphamide, and/or doxorubicin. Anticipatory CINV Occurs before patients receive their next chemotherapy treatment. Occurs after a negative past experience with chemotherapy. Nausea is generally more common than vomiting. Breakthrough CINV Occurs despite prophylactic treatment and/or requires rescue with antiemetic agents. Refractory CINV Occurs during subsequent treatment cycles in cases in which antiemetic prophylaxis and/or rescue failed in earlier cycles. a
Cisplatin-associated emesis reaches maximal intensity 48 to 72 hours after administration and may last 6 to 7 days. Source: Reference 1.
the cornerstone of prophylactic therapy for MEC and HEC include: dolasetron, granisetron, ondansetron, and palonosetron.2,16,17 These antiemetic agents have few adverse effects and no limiting toxicity at standard doses, with the most common side effects being headache, transient elevation of hepatic aminotransferase levels, and constipation.2 Dolasetron, granisetron, and on dansetron are effective in preventing acute emesis, but are relatively ineffective against delayed emesis, whereas palonosetron has been shown to prevent both.1 Based on a retrospective claims review of patients with lung cancer receiving cisplatin-based chemotherapy between 2005 and 2008, the group treated with palonosetron experienced a significantly lower risk for costly CINV than patients treated with any other 5-HT3 RA.18 Because of its efficacy in both acute and delayed CINV, palonosetron may also be effective in multiday chemotherapy and bone marrow transplantation settings. Further research will shed light on its potential in these areas.19 Neurokinin-1 receptor antagonists NK-1 RAs represent a relatively new Continued on page 12
December 2010 I VOL 3, NO 8
The Oncology Pharmacist