*Department of Pharmacy
Klinikum rechts der Isar der Technischen Universität München
Medical Economics Research Group
Merck & Co Inc
Whitehouse Station NJ, USA
Chemotherapy-induced nausea and vomiting (CINV) remains an important adverse effect of cancer chemotherapy. It is one of the most distressing side-effects of chemotherapy for patients, and it negatively impacts on patient wellbeing and quality of life. The economic consequences of CINV include the direct medical costs of treatment, as well as the indirect costs of decreased productivity and lost workdays. Prophylaxis of CINV is selected according to the emetogenicity of chemotherapy, as well as timing in relation to chemotherapy administration. Over the past 15 years, several new antiemetic agents have become available, including the 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonists and the neurokinin-1 (NK(1)) receptor antagonist aprepitant.(1) Quantifying the impact and cost of CINV in clinical practice is important to guide the allocation of resources for antiemetic prophylaxis.
Impact of delayed CINV at German cancer centres
From October 2001 to March 2003 we conducted a prospective, cross-sectional, cost-of-illness study of CINV at three office-based facilities and three hospitals in the province of Bavaria in Germany.(2) Our objectives were to evaluate treatment patterns and the outcomes of prophylactic care for CINV, as well as to measure direct and indirect costs of CINV in settings reflecting current medical practice in Germany.
Our study enrolled consecutive patients scheduled to receive cycle 1 or cycle 4 of chemotherapy with level 4 or 5 emetogenicity.(3) These levels of moderate and high emetogenicity are associated with 60–90% and >90% frequency of acute emesis, respectively, in the absence of antiemetic prophylaxis. Enrolled patients had to be chemotherapy-naive or without prior negative CINV experience, namely no history of vomiting (National Cancer Institute [NCI] grade 0(4)) and moderate nausea or less (NCI grade ≤2) with prior chemotherapy. Disabled patients, those with life expectancy <12 weeks and those with gastrointestinal disease causing vomiting or nausea were excluded.
Through review of medical charts and self-administered patient questionnaires, we collected information on occurrence and intensity of nausea and frequency of episodes of vomiting or dry heaves each day during the first five days after chemotherapy. The acute phase of CINV was defined as the first 24 hours after chemotherapy and the delayed phase as two to five days after. To calculate costs related to CINV, we collected information on: physician visits, emergency room visits and hospitalisations; over-the-counter medications; transportation or home help; and lost workdays because of CINV. Unit-cost data were derived from official tariff and price lists and hospital databases (in 2002 €). The full results of this study have been published.(2)
We recently performed a subanalysis of the direct costs of CINV incurred at the three hospitals.(5) The hospital perspective is important in Germany because of the introduction, in 2004, of the German refined diagnosis-related group (G-DRG) system,(6) which requires the optimisation of resource allocation in hospitals.
Characteristics of patients enrolled at three hospital centres
A total of 122 patients, 73 (60%) of them male, were evaluated for the hospital subanalysis. Their mean age was 56 years (standard deviation, 11 years). Neoplasia of the gastrointestinal tract was most common, affecting 64 patients (52%), followed by lung cancer (21 [17%]), breast cancer (17 [14%]), lymphoma (10 [8%]), other neoplasia (7 [6%]) and ovarian cancer (3 [2%]). Sixty-six percent of patients received a cisplatin- or carboplatin-containing chemotherapy regimen.
Frequency of CINV and patterns of antiemetic prophylaxis
Overall, CINV was reported during 73 of 137 (53%) evaluable chemotherapy cycles, with vomiting in 29 (21%) cycles and nausea in 70 (51%) cycles. CINV occurred in 20% and 50% of acute and delayed phases, respectively.
The administration of antiemetic prophylaxis adhered to the treatment guidelines available at the time7 for 90% and 71% of cycles for acute and delayed phases, respectively. Patterns of prophylactic care are summarised in Table 1. Adherence to guidelines for prophylaxis of delayed CINV was significantly (p<0.05) associated with a reduced rate of delayed vomiting, compared with nonadherence (12% vs 34%).
Resource utilisation and cost
One patient was rehospitalised and 12 patients received rescue therapy at the hospital because of CINV. Patients experiencing CINV incurred incremental costs of €27 from the hospital provider perspective. The main cost driver was staff time (mean cost, €25). Patients experiencing delayed CINV incurred significantly higher (p<0.05) costs (incremental cost of €29), relative to those without delayed CINV. Mean direct costs (prophylaxis and management of CINV) were €61 per cycle for each patient who experienced CINV or €48 per cycle for each patient overall, whether suffering from CINV or not.
Treatment characteristics that were associated with high costs attributable to CINV and reached the level of significance (p<0.05% vs reference group) were the following: cisplatin-containing regimen; the presence of delayed CINV; experience of vomiting (all grades).(2) Figure 1 represents an overview over the costs attributable to chemotherapy-induced nausea and vomiting (CINV), by subgroup.
We found that there was room for improvement at German hospitals in the processes and outcomes of care regarding adherence to guidelines for antiemetic prophylaxis, especially for delayed CINV. Many patients still experience CINV, with clinical and economic consequences. Patient wellbeing and economic savings are likely to be optimised by preventing delayed CINV. Optimisation of CINV management with regard to cost and, more importantly, quality of care will be a future challenge for German hospital pharmacists.
We would like to thank Dr Jutta Thödtmann and Dr Steffen Amann from our pharmacy department, Dr Florian Lordick and Prof Christian Peschel from our Third Medical Department and all participating study centres for their support
- Kris MG, Hesketh PJ, Herrstedt J, et al. Consensus proposals for the prevention of acute and delayed vomiting and nausea following high-emetic-risk chemotherapy. Support Care Cancer 2005;13:85-96.
- Ihbe-Heffinger A, Ehlken B, Bernard R, et al. The impact of delayed chemotherapy-induced nausea and vomiting on patients, health resource utilization and costs in German cancer centers. Ann Oncol 2004:15:526-36.
- Hesketh PJ, Kris MG, Grunberg SM, et al. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol 1997;15:103-9.
- Cancer Therapy Evaluation program. Common Toxicity Criteria, version 2.0. National Cancer Institute, March 1998. Accessible from: http://ctep.cancer.gov/reporting/CTC-3test.html. Or follow links from the CTEP home page at: http://ctep.info.nih.gov/
- Ihbe-Heffinger A, Ehlken B, Lordick F, et al. Chemotherapy-induced nausea and vomiting – outcomes of prophylactic care and costs in German hospital cancer centers. 10th Congress of the European Association of Hospital Pharmacists 2005;7: Abstract A4.
- Glocker S, Roeder N. Onkologie im G-DRG-System 2004. Der Onkologe 2003;9:1375-80.
- Gralla RJ, Osoba D, Kris MG, et al. Recommendations for the use of antiemetics: evidence-based, clinical practice guidelines. 1999;17:2971-94.
American Society of Clinical Oncology (ASCO)
Multinational Society of Supportive Care in Cancer (MASCC)
German refined Diagnosis Related Groups (G-DRG)