Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

SPECIAL REPORT

June 21, 2007

With the introduction of the serotonin antagonists (5-HT3 RA) over the past decades, significant progress has been made in the control of chemotherapy-induced nausea and vomiting (CINV). Yet as several studies have shown, acute and especially delayed nausea and vomiting are disturbingly prevalent after both moderately and highly emetogenic regimens, despite the use of effective antiemetics. The incidence of delayed nausea and vomiting is markedly underestimated by physicians and nurses caring for cancer patients, probably because it occurs outside of the immediate treatment setting. Poorly controlled CINV may cause patients to refuse further chemotherapy, resulting in a delayed administration of the requisite number of cycles or a reduction in the dose, which are likely to result in suboptimal outcomes. Canadian investigators found the cost of treating the consequences of CINV was significantly higher than the cost of treating patients without CINV, even when the cost of antiemetics was taken into consideration. From a patient perspective, CINV remains the most feared toxicity out of all potential chemotherapy-related effects and when it occurs, studies show it can greatly affect quality of life over the entire treatment interval. These findings support the need for better treatments to reduce CINV, especially delayed nausea and vomiting, which in turn could be expected to improve quality of life for cancer patients and significantly reduce CINV-associated costs.

In the absence of antiemetic medication, highly emetogenic chemotherapy causes vomiting in over 90% of patients within 24 hours of receiving treatment. Furthermore, despite the availability of modern antiemetics, a substantial proportion of patients still experience nausea and vomiting after chemotherapy, particularly during the delayed phase (Lachaine et al. Suppor Cancer Ther 2005;2(3)181-7).

Assessing Prevalence and Impact: Study Findings

In a study designed to assess the prevalence and impact of acute and especially delayed nausea and vomiting, investigators recruited 323 patients in Ontario and Quebec scheduled to undergo any highly emetogenic regimen (e.g. cisplatin or carboplatin/gemcitabine).

Either a nurse or a pharmacist recorded the occurrence of nausea or vomiting during treatment. Patients were also asked to record the number of vomiting episodes experienced each day over a five-day period, as well as the degree of nausea using a visual analogue scale (VAS). On this scale, only nausea episodes rated as at least 25 mm on a 100-mm scale were considered significant. Quality of life was measured using the validated Functional Living Index-Emesis (FLIE) questionnaire.

“Most patients received a serotonin antagonist at the hospital, usually in combination with corticosteroids,” investigators noted. After day 1 of chemotherapy, approximately 40% of patients continued to take a serotonin antagonist. Results from 266 completed questionnaires indicated that 47% of all patients experienced nausea or vomiting, with the incidence at 44% being “particularly high” during the delayed period. For this study, acute nausea and vomiting was defined as that which occurred within the first 24 hours following chemotherapy, while delayed nausea and vomiting was defined as that which occurred between days 2 and 5 following treatment.

“All but one of the patients received an antiemetic medication while they were in the hospital to receive chemotherapy and a majority also took antiemetic agents as outpatients,” researchers observed.

Cost and Absenteeism Associated with CINV

As a result of delayed chemotherapy-induced nausea and vomiting (CINV) over the following five days after receiving chemotherapy, patients required a total of four emergency visits and 10 physician visits; two patients required hospitalization. “These encounters with the health care system were estimated to cost $5680, based on prevailing costs in Ontario in 2003,” investigators stated. Among patients who experienced vomiting or retching, the mean cost of emergency visits, physician visits and hospitalization was $65.55, they added.

Investigators also assessed the amount of time and money CINV cost both patients and their caregivers. Patients reported losing an average of 29.4 hours because of CINV, 44% of which was lost time from paid employment, the remainder coming from leisure time. “When considering only patients who experienced emesis [with or without nausea] and their caregivers, an average of 22.3 hours were lost, valued at $402.74,” investigators reported. The total difference in cost between those who experienced CINV and those who did not, including productivity losses, ranged from $294.38 to $591.72, depending on whether leisure time was considered.

Importantly as well, FLIE results indicated that quality of life was significantly diminished among patients who experienced nausea or vomiting. Among patients who did not, the average FLIE score remained similar prior to and after chemotherapy at 122.7 and 121.7, respectively. In contrast, among those who did experience CINV, the average FLIE score dropped significantly from 118.5 before chemotherapy to 90.6 after.

As investigators discussed, the reason why many clinicians appear reluctant to prescribe serotonin antagonists more than 24 hours after patients undergo chemotherapy may be related to their “limited efficacy” for preventing delayed CINV. Thus, “as observed in this study, control of CINV remains a problem for many patients receiving highly emetogenic chemotherapy,” investigators concluded, as almost half of all patients in this study experienced at least one or more episodes of vomiting or significant nausea, despite using antiemetic therapy. CINV also represents a “considerable economic burden” for patients, their caregivers and the healthcare system, they added. Perhaps most importantly, inadequate control of CINV may prompt patients to refuse further treatment with what may well be the most clinically effective regimen, or lead to either a delay in administration or a dose reduction, “all of which can result in suboptimal clinical outcomes,” researchers observed.

Caregivers’ Perception of CINV Incidence

Delayed nausea and vomiting are markedly underestimated by physicians and nurses who care for cancer patients and was underscored in a previously published study (Grunberg et al. Cancer 2004;100(10):2261-8). Twenty-four physicians and nurses from 14 different practices in both the US and Europe were asked to predict the incidence of acute and delayed nausea and vomiting after moderately and highly emetogenic chemotherapy regimens. Some 97% of all patients received a serotonin antagonist, typically accompanied by a corticosteroid, both usually given for three days.

Professional predictions of acute nausea (34%) and vomiting (17%) after highly emetogenic regimens were very accurate and corresponded closely with the observed incidence. In contrast, the predicted incidence of delayed nausea (39%) was markedly lower than the observed incidence (60%), as was the predicted incidence of delayed vomiting (22%) vs. the observed incidence (50%).

“The most striking finding of the current study was the underestimation of the current incidence of delayed nausea and emesis in their own practices by experienced physicians and nurses,” investigators reported, adding that this was true for both moderately and highly emetogenic regimens. As they pointed out, since “effective treatment for a problem cannot be administered unless caregivers realize that the problem exists, new antiemetic agents, such as the NK-1 antagonists and longer-acting antiemetics, may ameliorate these problems and help patients maintain their functional status during chemotherapy.”

Summary

Good antiemetic control is possible, yet CINV occurs in a substantial proportion of patients undergoing moderately to highly emetogenic regimens. This is partly due to an underappreciation of the actual prevalence of delayed nausea and vomiting days after treatment but patients themselves may not complain, as they tend to expect this to occur with chemotherapy and suffer in silence. Their discomfort comes at considerable cost, however, both in terms of days lost from productive activities as well as their need for medical attention and its attendant costs. A deeper appreciation of the prevalence of CINV, coupled with proper prophylactic antiemetic strategies can substantially ameliorate quality of life for patients undergoing emetogenic chemotherapy. Coping with cancer and cancer treatment is physically and emotionally difficult for patients without the added burden of CINV.

Questions and Answers with Dr. Marla Shapiro

Q: Why don’t patients let physicians know when they develop CINV?

A: Patients often do not see their physicians when they develop delayed CINV and they do not call because they think they have to “tough it out.” They also may not retain their primary care physician throughout chemotherapy so there is a lack of an identifiable person who they feel they can easily call.

Q: Was your own antiemetic regimen adequate to control your CINV when you had breast cancer?

A: I had excellent prophylaxis but despite that, I can tell you CINV does impact on your life, not only in terms of how it affects your daily activities but on secondary end points, such as weight loss and weakness related to the nausea and vomiting. Not only could I not practice, but it impacted on my ability to be the primary caregiver at home. Not being able to function at home because of nausea just makes you that much more debilitated.

Questions and Answers with Dr. David G. Warr

Q: Is CINV actually more prevalent than many oncologists think? If so, is there a reason for this misconception?

A: Yes [it is more prevalent]. We like to be optimistic, and the older oncologists remember what progress has been made since 1990. Also, if you feel you do not have anything you can add, you are not as likely to be sensitive to the problem.

Q: Grunberg et al. reported that physicians and nurses significantly underestimated the incidence of delayed nausea and emesis after both moderately and highly emetogenic chemotherapy. How could this problem best be corrected?

A: I do not think exact percentages are of any importance, so underestimating per se is irrelevant. Even the low estimates are high enough to warrant asking about if you feel you can do something about it, and if you think it is something that is distressing to the patient. The impact upon quality of life and the treatment options, if you do recognize it, need to be emphasized.