Support Care Cancer (2015) 23:251–252 DOI 10.1007/s00520-014-2371-4
EDITORIAL
Assessing the burden and management of chemotherapy induced emesis in the Asia/Pacific region Ian Olver
Received: 15 June 2014 / Accepted: 24 July 2014 / Published online: 3 August 2014 # Springer-Verlag Berlin Heidelberg 2014
The success of antiemetic prophylaxis to alleviate chemotherapy-induced nausea and vomiting (CINV) has increased with the addition of two classes of drugs, the 5hydroxytryptamine3 receptor antagonists (5HT3-RA) and the neurokinin 1 receptor antagonists (NK1-RA). Consensus guidelines, regularly updated over decades, have been available to provide advice on the management of acute and delayed emesis [1]. Most studies of CINV have centred on Europe and the USA. A European study has examined the impact of guidelines, and there is no reason to believe that the Asian/Pacific region would differ, although there has been a suggestion of greater severity of emesis in Asian women in a US study [2, 3]. The Pan Australasia ChemoTherapy InduCed Emesis (PrACTICE) Study is a prospective descriptive study reporting the burden of emesis and practice patterns of management across 31 centres in 6 countries in Southeast Asia, China, India, Singapore, South Korea, Taiwan and Australia. The logistic exercise is impressive and demonstrates the utility of using electronic case report forms and standardising the recording of the patients’ experience, with the MASCC Antiemesis Tool (MAT) and the ASCO Quality Oncology Practice Initiative measures [4, 5]. Although direct comparisons with studies in Europe are not possible, in general, the similarities are more striking than the differences. The prevalence of risk factors for emesis is comparable although perhaps with a higher incidence of reported non-drinkers (80 %) in the Asia/Pacific study than would be expected elsewhere. The overall control of emesis approaching 70 % is very good and higher than the European study for chemotherapy of high or moderate emetic potential (HEC and MEC) while the opposite applied to control of I. Olver (*) Cancer Council Australia, Sydney, NSW, Australia e-mail: [email protected]
nausea. In the region, there is a similar control of acute emesis between countries but the control of delayed emesis has a range spanning from 57 to 88 %. Unfortunate constraints on this comparison are that three of the countries failed to meet their accrual targets and China had not approved the funding of neurokinin 1 receptor antagonists, which is quite a different situation than the variations in the way clinicians practice or adhere to guidelines that may explain differences between other countries. Moreover, even in countries which had approved the drugs, the indications for which they were approved may differ. Doxorubicin and anthracycline was for many years misclassified as MEC but now is listed as HEC particularly for its common use in breast cancer. Overall, the acute control of HEC and MEC is superior to that of delayed emesis. The combination of a 5HT3 and steroids makes a significant impact on acute emesis, and the 5HT3 antagonist was used for 96 % with a steroid 87 %, but makes less impact on delayed emesis in HEC where the addition of an NK1 led to superior results but was only used for 47 % patients, with great variation by country. Similar results were recorded for the acute phase in MEC but for the delayed phase, only 69 % were prescribed an antiemetic, including a 5HT3 (41 %) steroid (37 %) and only 4 % received an NK1 receptor antagonist. However, the long-acting 5HT3 drugs influence delayed emesis more than those with shorter action in MEC and steroids can also be effective in this group in controlling delayed emesis. There was great variation between countries on whether antiemetics were prescribed for the delayed emesis with MEC. Vomiting is better controlled than nausea as expected, since the drugs, such as the 5HT3 receptor antagonists, have less impact on nausea in most reported studies. Nausea is a subjective phenomenon. The report of far less nausea in India than Australia may be due to better control of nausea or perhaps a different patient understanding of what the experience of nausea is, leading to a different level of reporting.
252
Recent studies, in attempting to explain the poorer control of nausea, have suggested that it is, or is at least associated with, a cluster of symptoms with differences between patients in how they experience it [6]. In a study by Grunberg et al., it was found that physicians underestimated delayed nausea by up to 28 % [7]. In the PrACTICE Study, the more striking results were that over half of the clinicians overestimated vomiting but underestimated nausea. A strength of the PrACTICE Study is that it recorded nausea and vomiting with chemotherapy cycles 2 and 3. This enabled an analysis of the impact of nausea and vomiting in a previous cycle affecting a subsequent cycle and to record anticipatory emesis. Over the study, the odds of experiencing emesis in a subsequent cycle were 12.7 % greater for those who had experienced emesis compared to those who had not in a previous cycle. This is similar to findings from Europe and simply underlines the importance of using optimal antiemetics from the first cycle [8]. Overall, though, only 2 % chemotherapy doses were reduced in subsequent cycles primarily because of nausea and vomiting. There was a marked difference between countries in the propensity to dose reduce, this mainly confined to South Korea and Taiwan. This is particularly problematic if administering potentially curative chemotherapy. The incidence of anticipatory nausea (7.9 and 8.3 %) was higher than that of anticipatory emesis (1.5 and 2.3 %) prior to cycles 2 and 3. The strongest predictors were CINVor anxiety in previous cycles. The expectation of nausea resulted in the experience of nausea before cycle 1 and patients who had clinically significant nausea in prior cycles had an odds ratio of 3.95 of developing nausea in subsequent cycles compared to those having had no prior nausea. Expectation of toxicities has been correlated with a greater chance of experiencing side effects, particularly those which are subjective, increasing anxiety [9]. Studies like the PrACTICE Study, although not specifically evaluating compliance with guidelines, demonstrate the importance of evidence-based rather than consensus guidelines which can be widely disseminated and taken up to reduce the variations in practice that result in inferior outcomes. Guidelines need to be regularly updated to keep pace with the evidence, hence the move to digital guidelines [10]. Studies should then evaluate the impact of such guidelines. Comparisons between countries may also be helpful in advocating for
Support Care Cancer (2015) 23:251–252
the listing of active drugs in countries where they are not available. Conflict of interest I have no conflicts of interest relating to the content of this editorial.
References 1. Jordan K, Gralla R, Jahn F, Molassiotis A (2014) International antiemetic guidelines on chemotherapy induced nausea and vomiting (CINV): content and implementation in daily routine practice. Eur J Pharmacol 722:197–202. doi:10.1016/j.ejphar.2013.09.073 2. Aapro M, Molassiotis A, Dicato M, Pelaez I, Rodriguez-Lescure A, Pastorelli D, Ma L, Burke T, Gu A, Gascon P, Roila F (2012) The effect of guideline-consistent antiemetic therapy on chemotherapyinduced nausea and vomiting (CINV): the Pan European Emesis Registry (PEER). Ann Oncol 23(8):1986–1992. doi:10.1093/ annonc/mds021 3. Bourdeanu L, Frankel P, Yu W, Hendrix G, Pal S, Badr L, Somlo G, Luu T (2012) Chemotherapy-induced nausea and vomiting in Asian women with breast cancer receiving anthracycline-based adjuvant chemotherapy. J Support Oncol 10(4):149–154. doi:10.1016/j. suponc.2011.10.007 4. Molassiotis A, Coventry PA, Stricker CT, Clements C, Eaby B, Velders L, Rittenberg C, Gralla RJ (2007) Validation and psychometric assessment of a short clinical scale to measure chemotherapyinduced nausea and vomiting: the MASCC antiemesis tool. J Pain Symptom Manag 34(2):148–159 5. American Society of Clinical Oncology (ASCO) the Quality Oncology Practice Initiative (QOPI). http://qopi.asco.org/. Accessed 3 June 2014 6. Olver IN, Eliott JA, Koczwara B (2014) A qualitative study investigating chemotherapy-induced nausea as a symptom cluster. Support Care Cancer. doi:10.1007/s00520-014-2276-2282 7. Grunberg SM, Deuson RR, Mavros P, Geling O, Hansen M, Cruciani G, Daniele B, De Pouvourville G, Rubenstein EB, Daugaard G (2004) Incidence of chemotherapy-induced nausea and emesis after modern antiemetics. Cancer 100(10):2261–2268 8. Molassiotis A, Aapro M, Dicato M, Gascon P, Novoa SA, Isambnert M, Burke TA, Gu A, Rolia F (2013) Evaluation of risk factors predicting chemotherapy-related nausea and vomiting: results from a European prospective observational study. J Pain Symptom Manag. doi:10.1016/j.jpainsymman.2013.06.012 9. Roscoe JA, Bushunow P, Morrow GR, Hickok JT, Kuebler PJ, Jacobs A, Banerjee TK (2004) Patient expectation is a strong predictor of severe nausea after chemotherapy: a University of Rochester Community Clinical Oncology Program study of patients with breast carcinoma. Cancer 101:2701–2708 10. Olver IN, von Dincklage JJ (2013) It is time for guidelines to enter the digital age. Med J Aust 199(9):569–570
EDITORIAL
Assessing the burden and management of chemotherapy induced emesis in the Asia/Pacific region Ian Olver
Received: 15 June 2014 / Accepted: 24 July 2014 / Published online: 3 August 2014 # Springer-Verlag Berlin Heidelberg 2014
The success of antiemetic prophylaxis to alleviate chemotherapy-induced nausea and vomiting (CINV) has increased with the addition of two classes of drugs, the 5hydroxytryptamine3 receptor antagonists (5HT3-RA) and the neurokinin 1 receptor antagonists (NK1-RA). Consensus guidelines, regularly updated over decades, have been available to provide advice on the management of acute and delayed emesis [1]. Most studies of CINV have centred on Europe and the USA. A European study has examined the impact of guidelines, and there is no reason to believe that the Asian/Pacific region would differ, although there has been a suggestion of greater severity of emesis in Asian women in a US study [2, 3]. The Pan Australasia ChemoTherapy InduCed Emesis (PrACTICE) Study is a prospective descriptive study reporting the burden of emesis and practice patterns of management across 31 centres in 6 countries in Southeast Asia, China, India, Singapore, South Korea, Taiwan and Australia. The logistic exercise is impressive and demonstrates the utility of using electronic case report forms and standardising the recording of the patients’ experience, with the MASCC Antiemesis Tool (MAT) and the ASCO Quality Oncology Practice Initiative measures [4, 5]. Although direct comparisons with studies in Europe are not possible, in general, the similarities are more striking than the differences. The prevalence of risk factors for emesis is comparable although perhaps with a higher incidence of reported non-drinkers (80 %) in the Asia/Pacific study than would be expected elsewhere. The overall control of emesis approaching 70 % is very good and higher than the European study for chemotherapy of high or moderate emetic potential (HEC and MEC) while the opposite applied to control of I. Olver (*) Cancer Council Australia, Sydney, NSW, Australia e-mail: [email protected]
nausea. In the region, there is a similar control of acute emesis between countries but the control of delayed emesis has a range spanning from 57 to 88 %. Unfortunate constraints on this comparison are that three of the countries failed to meet their accrual targets and China had not approved the funding of neurokinin 1 receptor antagonists, which is quite a different situation than the variations in the way clinicians practice or adhere to guidelines that may explain differences between other countries. Moreover, even in countries which had approved the drugs, the indications for which they were approved may differ. Doxorubicin and anthracycline was for many years misclassified as MEC but now is listed as HEC particularly for its common use in breast cancer. Overall, the acute control of HEC and MEC is superior to that of delayed emesis. The combination of a 5HT3 and steroids makes a significant impact on acute emesis, and the 5HT3 antagonist was used for 96 % with a steroid 87 %, but makes less impact on delayed emesis in HEC where the addition of an NK1 led to superior results but was only used for 47 % patients, with great variation by country. Similar results were recorded for the acute phase in MEC but for the delayed phase, only 69 % were prescribed an antiemetic, including a 5HT3 (41 %) steroid (37 %) and only 4 % received an NK1 receptor antagonist. However, the long-acting 5HT3 drugs influence delayed emesis more than those with shorter action in MEC and steroids can also be effective in this group in controlling delayed emesis. There was great variation between countries on whether antiemetics were prescribed for the delayed emesis with MEC. Vomiting is better controlled than nausea as expected, since the drugs, such as the 5HT3 receptor antagonists, have less impact on nausea in most reported studies. Nausea is a subjective phenomenon. The report of far less nausea in India than Australia may be due to better control of nausea or perhaps a different patient understanding of what the experience of nausea is, leading to a different level of reporting.
252
Recent studies, in attempting to explain the poorer control of nausea, have suggested that it is, or is at least associated with, a cluster of symptoms with differences between patients in how they experience it [6]. In a study by Grunberg et al., it was found that physicians underestimated delayed nausea by up to 28 % [7]. In the PrACTICE Study, the more striking results were that over half of the clinicians overestimated vomiting but underestimated nausea. A strength of the PrACTICE Study is that it recorded nausea and vomiting with chemotherapy cycles 2 and 3. This enabled an analysis of the impact of nausea and vomiting in a previous cycle affecting a subsequent cycle and to record anticipatory emesis. Over the study, the odds of experiencing emesis in a subsequent cycle were 12.7 % greater for those who had experienced emesis compared to those who had not in a previous cycle. This is similar to findings from Europe and simply underlines the importance of using optimal antiemetics from the first cycle [8]. Overall, though, only 2 % chemotherapy doses were reduced in subsequent cycles primarily because of nausea and vomiting. There was a marked difference between countries in the propensity to dose reduce, this mainly confined to South Korea and Taiwan. This is particularly problematic if administering potentially curative chemotherapy. The incidence of anticipatory nausea (7.9 and 8.3 %) was higher than that of anticipatory emesis (1.5 and 2.3 %) prior to cycles 2 and 3. The strongest predictors were CINVor anxiety in previous cycles. The expectation of nausea resulted in the experience of nausea before cycle 1 and patients who had clinically significant nausea in prior cycles had an odds ratio of 3.95 of developing nausea in subsequent cycles compared to those having had no prior nausea. Expectation of toxicities has been correlated with a greater chance of experiencing side effects, particularly those which are subjective, increasing anxiety [9]. Studies like the PrACTICE Study, although not specifically evaluating compliance with guidelines, demonstrate the importance of evidence-based rather than consensus guidelines which can be widely disseminated and taken up to reduce the variations in practice that result in inferior outcomes. Guidelines need to be regularly updated to keep pace with the evidence, hence the move to digital guidelines [10]. Studies should then evaluate the impact of such guidelines. Comparisons between countries may also be helpful in advocating for
Support Care Cancer (2015) 23:251–252
the listing of active drugs in countries where they are not available. Conflict of interest I have no conflicts of interest relating to the content of this editorial.
References 1. Jordan K, Gralla R, Jahn F, Molassiotis A (2014) International antiemetic guidelines on chemotherapy induced nausea and vomiting (CINV): content and implementation in daily routine practice. Eur J Pharmacol 722:197–202. doi:10.1016/j.ejphar.2013.09.073 2. Aapro M, Molassiotis A, Dicato M, Pelaez I, Rodriguez-Lescure A, Pastorelli D, Ma L, Burke T, Gu A, Gascon P, Roila F (2012) The effect of guideline-consistent antiemetic therapy on chemotherapyinduced nausea and vomiting (CINV): the Pan European Emesis Registry (PEER). Ann Oncol 23(8):1986–1992. doi:10.1093/ annonc/mds021 3. Bourdeanu L, Frankel P, Yu W, Hendrix G, Pal S, Badr L, Somlo G, Luu T (2012) Chemotherapy-induced nausea and vomiting in Asian women with breast cancer receiving anthracycline-based adjuvant chemotherapy. J Support Oncol 10(4):149–154. doi:10.1016/j. suponc.2011.10.007 4. Molassiotis A, Coventry PA, Stricker CT, Clements C, Eaby B, Velders L, Rittenberg C, Gralla RJ (2007) Validation and psychometric assessment of a short clinical scale to measure chemotherapyinduced nausea and vomiting: the MASCC antiemesis tool. J Pain Symptom Manag 34(2):148–159 5. American Society of Clinical Oncology (ASCO) the Quality Oncology Practice Initiative (QOPI). http://qopi.asco.org/. Accessed 3 June 2014 6. Olver IN, Eliott JA, Koczwara B (2014) A qualitative study investigating chemotherapy-induced nausea as a symptom cluster. Support Care Cancer. doi:10.1007/s00520-014-2276-2282 7. Grunberg SM, Deuson RR, Mavros P, Geling O, Hansen M, Cruciani G, Daniele B, De Pouvourville G, Rubenstein EB, Daugaard G (2004) Incidence of chemotherapy-induced nausea and emesis after modern antiemetics. Cancer 100(10):2261–2268 8. Molassiotis A, Aapro M, Dicato M, Gascon P, Novoa SA, Isambnert M, Burke TA, Gu A, Rolia F (2013) Evaluation of risk factors predicting chemotherapy-related nausea and vomiting: results from a European prospective observational study. J Pain Symptom Manag. doi:10.1016/j.jpainsymman.2013.06.012 9. Roscoe JA, Bushunow P, Morrow GR, Hickok JT, Kuebler PJ, Jacobs A, Banerjee TK (2004) Patient expectation is a strong predictor of severe nausea after chemotherapy: a University of Rochester Community Clinical Oncology Program study of patients with breast carcinoma. Cancer 101:2701–2708 10. Olver IN, von Dincklage JJ (2013) It is time for guidelines to enter the digital age. Med J Aust 199(9):569–570
