MGluR patients, however, who had a CR and good control of nausea in the acute period and subsequently developed emesis and nausea in the delayed period, suggesting differences in the mechanisms of acute and delayed CINV. The main period of failure in CR or control of nausea in the delayed period in this study was day 2 or 3, which is consistent with a number of previous studies.18,28 One hundred fifty seven of the 241 patients received at least four cycles of chemotherapy, and the high level of CR, the level of control of nausea, and the lack of adverse events noted in cycle 1 were maintained over the multiple cycles of chemotherapy for each of the antiemetic regimens. The high level of control of CINV in the delayed period in this study appears to be due to the combination of olanzapine and palonosetron. Olanzapine has been shown in previous studies to be an effective agent at controlling delayed CINV.6 8 A Gamma Secretase recent study14 demonstrated that when administered with dexamethasone before HEC, palonosetron exerts better efficacy against CINV than granisetron in the delayed phase. The high level of control of delayed CINV in this study was achieved without the use of dexamethasone in the delayed period, potentially eliminating the short and long term toxicities of dexamethasone experienced by some patients.
animal models.37,38 The effect of olanzapine on this receptor as well as other IkB Signaling dopamine and serotonin receptors may explain its efficacy in CINV. The relative contribution of the effects of various antiemetics at central and peripheral sites to the control of acute and delayed nausea and emesis cannot be determined at this time based on available studies.2,4 In this study, for the doses given, olanzapine was not associated with significant sedation, weight gain, or induction of significant hyperglycemia. These effects have been associated with olanzapine given for longer periods of time. There are also economic benefits of olanzapine. The 4 day treatment with olanzapine is approximately 10% 20% of the cost of the 3 day aprepitant treatment.39 The results of this study demonstrate that in patients receiving HEC, the OPD regimen is equivalent to the APD regimen in controlling emesis and the use of rescue Temsirolimus medication but that the OPD regimen is significantly better at controlling nausea. The trial arms in the study were not blinded.
It is unlikely that the lack of blinding in the trial would affect the trial outcome since all of the patients in the study were chemotherapy naive and none had previously received either of the antiemetic regimens. Future investigations may explore the efficacy of olanzapine with or without dexamethasone in the delayed period for clinical situations such as multiday chemotherapy or highdose chemotherapy and stem cell transplantation. Acknowledgments: Supported by the Walther Cancer Foundation and the Reich Endowment for the Care of the Whole Patient. Cisplatin is a platinum based chemotherapeutic agent that has been used widely for several malignancies. One of the most undesirable effects during treatment with cisplatin is severe emesis, which often limits its therapeutic use. Indeed, cisplatin is classified in the highest emetic risk group according to American Society of Clinical Oncology guidelines.