Reply to T.L. Ng et al and L. Celio et al
Authors: Fausto Roila, Sonia Fatigoni, Enzo Ballatori
Journal: Journal of Clinical Oncology (2014)

We thank Ng et al 1 not only for their valuable comments on our study, 2 but also for bringing up the problems concerning the end points in antiemetic research.In our study, we chose to consider several end points only to allow the reader to compare our results with those obtained from other trials.We agree with the authors about the existence of too many end points in antiemetic research, as well as about the lack of a standard outcome measure that can offer immediate application in daily clinical practice.The problem was discussed and unanimously defined during the 1997 Perugia Consensus Conference on antiemetics. 3Unfortunately, these guidelines have often been disregarded.The primary end points are really only two: no vomiting and no nausea.Between them there exists a strong correlation that should be analyzed to improve our understanding of the effects of antiemetic drugs, and not eliminated when using a compound (mixed) response. 4In antiemetic research, the use of compound responses is always dangerous, mainly because they do not allow analysis of the relationship between the combined responses.Ng et al 1 described the end points found in published antiemetic studies.Most of them combine efficacy response with the rescue, which instead depends not only on the patient's condition, but also on the possibility of obtaining a rescue treatment.Patients generally suffer from delayed emesis at home, and it is not always possible for them to obtain immediate medical intervention.Moreover, these end points refer to a period of 0 to 120 hours.Because of the existence of a dependent effect on delayed emesis of the results observed in acute phase, it is difficult to understand if a drug is efficacious only in the acute phase or also in the delayed phase.This is precisely the purpose of scientific research: to identify all of the effects of a drug.We thank Celio et al 5 for their comments.Our answers are as follows:First, both the European Society of Medical Oncology/ Multinational Association of Supportive Care in Cancer and the American Society of Clinical Oncology guidelines recommend a 5-hydroxytryptamine 3 receptor antagonist (not necessarily palonosetron) for the prophylaxis of anthracyclines plus cyclophosphamide (AC) -induced emesis.Because of the lack of adequate funding we chose palonosetron because it was provided by Helsinn Healthcare, Lugano, Switzerland, and Italfarmaco, Milan, Italy.Second, we disagree with the statement by Celio et al 5 that "the choice of palonosetron represents a methodologic pitfall for a trial designed to target delayed emesis," because both groups of patients received palonosetron.Third, Celio et al 5 stated that, in our study, there was an ". . .absence of any attempt to place the findings in the context of other existing and relevant knowledge."We did discuss the results of the studies by Aapro et al 6 and Celio et al 7 on palonosetron as a "dexamethasone-sparing drug" in preventing delayed emesis.These studies seem to show the ineffectiveness of dexamethasone (the nonsignificant difference with respect to the placebo cannot be regarded in any other way) as an antiemetic prophylaxis in patients undergoing treatment with AC or moderately emetogenic chemotherapy.Our opinion is that these two studies 6,7 have notable shortcomings.Both