Ithimakin, S., Runglodvatana, K., Nimmannit, A., Akewanlop, C., Srimuninnimit, V., Keerativitayanan, N., . . . Laocharoenkeat, A. (2012). Randomized, double-blinded, placebo-controlled trial of ondansetron plus dexamethasone with or without metoclopramide as antiemetic prophylaxis in patients receiving high-dose cisplatin in medical practice. Supportive Care in Cancer, 20, 849-855.

To evaluate the effectiveness and safety of adding metoclopramide to the standard ondansetron and dexamethasone antiemetic regimen for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) among patients receiving cisplatin-based therapy

Patients were randomized (stratified by gender and age group) to a treatment or control group. All patients received ondansetron and dexamethasone prior to cisplatin and on the four subsequent days (days 2-5). Patients received either 20 mg of metoclopramide or placebo orally four times daily on days 2-5. Rescue treatment (including metoclopramide) was allowed based on the decision of the primary physician. On day 2, blinded data collectors documented the first emetic episode and frequency of emesis, severity of nausea and vomiting, side effects, and rescue antiemetic medications. On day 5, patients reported satisfaction of emetic treatment and quality of life.

• The study consisted of 162 patients.
• Just more than half (51%) of patients were 50 years old or older.
• The sample was 73% male and 27% female.
• The majority of patients (74%) had been diagnosed with head and neck cancer. Other cancers included gastrointestinal tract (10%), lung (5%), and sarcoma (5%).
• All patients received more than 50 mg/m² of cisplatin for their first dose.

The study was conducted at a single site, inpatient setting in Thailand.

All patients were in active antitumor treatment.

This was a randomized, double-blinded, placebo-controlled study.

• Measurement instruments for the first emetic episode, frequency of emesis, side effects, and rescue antiemetic medication were not reported in the article. 
• Common Terminology Criteria for Adverse Events, version 3.0, was used to measure severity of nausea and vomiting. 
• The Functional Living Index Emesis was used to document patient-reported satisfaction and quality of life.

• Before random assignment to the study, significantly more patients in the placebo group (30%) required rescue antiemetic medication for treatment of acute emesis (p = 0.04), and significantly more placebo group patients received metoclopramide as a rescue antiemetic (p = 0.02).
• No differences were found among treatment and placebo groups for patients who developed CINV, the severity of CINV, time to first emetic episode, or impact of CINV on daily life.  The only difference noted between groups was the proportion of patients that required rescue antiemetic medication, with significantly less medication used in the treatment group versus the placebo group (p = 0.05). 
• Metoclopramide was well tolerated with no difference in toxicities among the two groups.  Only one patient receiving metoclopramide had extrapyramidal effects.

No antiemetic benefit was found by adding metoclopramide to the standard ondansetron and dexamethasone regimen during cisplatin-based therapy; however, results are difficult to interpret because of a significant number of control patients receiving metoclopramide prior to the start of the study.

• Notable baseline sample group differences existed.
• Patients were allowed to receive metoclopramide for treatment of acute emesis prior to study randomization; therefore, some patients in the placebo group received metoclopramide and were not technically a control group.

A high number of patients in the placebo group developed anticipatory vomiting prior to the start of treatment, which illustrates the importance of performing thorough assessments prior to the start of chemotherapy and providing education prior to the start of the next course of chemotherapy.