Medline ® Abstracts for References 2,3
of 'Pathophysiology and prediction of chemotherapy-induced nausea and vomiting'
Drug treatment of chemotherapy-induced delayed emesis.
Tavorath R, Hesketh PJ
Chemotherapy-induced emesis has a major adverse impact on patients undergoing therapy for various malignancies, and this has led to considerable research in this field. Most investigative efforts have concentrated on the acute phase of emesis that occurs within the first 24 hours after chemotherapy, and significant strides forward have been made with this problem. Better control of acute emesis with newer agents such as the serotonin 5-HT3 receptor antagonists has focused increasing attention on a second phase of nausea and vomiting, known as delayed emesis, which occurs more than 24 hours after chemotherapy. This delayed phase is often not as well controlled with the antiemetics that have proven effective in acute emesis, and contributes to the distress associated with emetogenic chemotherapy. Most of the available data on delayed emesis are based on studies with cisplatin-based regimens, with much less understanding of delayed nausea and vomiting induced by non-cisplatin-based chemotherapy. Nevertheless, it is evident that the patterns of delayed emesis associated with cisplatin and non-cisplatin chemotherapy have distinct differences. The control of delayed emesis, especially following cisplatin, remains a therapeutic challenge. Contributing to the lack of progress has been the absence of an experimental model to help in elucidating the pathophysiology of delayed emesis and in the evaluation of new therapeutic approaches. The combination of metoclopramide and dexamethasone, although superior to placebo in randomised trials, provides only moderate control of delayed emesis following high-dose cisplatin. The 5-HT3 receptor antagonists that are effective in the prevention of acute emesis with cisplatin have failed to make a major impact on the delayed phase. When combined with dexamethasone, these agents provide no additional benefit to that achieved using dexamethasone alone or dexamethasone combined with metoclopramide. With non-cisplatin chemotherapy, corticosteroids and 5-HT3 receptor antagonists are the most useful agents. Efforts are ongoing to identify more effective treatments for delayed emesis. One novel approach involves the blockade of substance P binding to neurokinin-1 (NK1) receptors. This article reviews what is currently known about chemotherapy-induced delayed emesis, with a focus on treatment strategies.
Section of Medical Oncology, St Elizabeth's Medical Center, Boston, Massachusetts, USA.
Prospective evaluation of the incidence of delayed nausea and vomiting in patients with colorectal cancer receiving oxaliplatin-based chemotherapy.
Hesketh PJ, Sanz-Altamira P, Bushey J, Hesketh AM
Support Care Cancer. 2012;20(5):1043. Epub 2011 May 9.
PURPOSE: This study sought to prospectively determine the frequency of delayed nausea and vomiting with oxaliplatin-based chemotherapy following day 1 prophylaxis with a 5-HT-(3) receptor antagonist and dexamethasone.
METHODS: Patients with colon cancer,≥age 18, with a performance status≤2, receiving oxaliplatin (85-100 mg/m(2)) as part of a standard folinic acid, 5-fluorouracil, oxaliplatin regimen for the first time were eligible. All patients received a 5-HT(3) receptor antagonist and dexamethasone 20 mg on day 1 prior to oxaliplatin. No routine prophylaxis for delayed emesis was given. Antiemetic outcome was recorded in patient-completed diaries for the 120-h study period following oxaliplatin administration. Primary endpoint was frequency of delayed (24-120 h) emesis (vomiting/retching).
RESULTS: Forty-one patients were enrolled and 39 are evaluable. Median age was 70 (34-85) and the female/male ratio was 20:19. Four patients (10%) experienced vomiting or retching during the delayed period. One patient vomited during the first 24 h after oxaliplatin. The overall (120 h) no emesis rate was 87% (34/39). Twenty-one patients (54%) developed delayed nausea. Nine patients had moderate or severe nausea. Eighteen patients (46%) took rescue antiemetics during the delayed period. Delayed and overall complete response (no emesis or use of rescue antiemetics) rates were 54% and 49%, respectively.
CONCLUSIONS: The use of a 5-HT(3) antagonist and dexamethasone prior to oxaliplatin results in excellent control of nausea and vomiting (CR-90%) during the 24 h after chemotherapy. However, without further antiemetic treatment, complete response in the delayed period decreased to 54%. This study supports the need for routine antiemetic prophylaxis for delayed nausea and vomiting following oxaliplatin-based chemotherapy.
Department of Hematology and Oncology, Lahey Clinic Medical Center, 41 Mall Road, Burlington, MA 01805, USA. Paul.Hesketh@lahey.org