Ueda, H., Shimono, C., Nishimura, T., Shimamoto, M., & Yamaue, H. (2014). Palonosetron exhibits higher total control rate compared to first-generation serotonin antagonists and improves appetite in delayed-phase chemotherapy-induced nausea and vomiting. Molecular and Clinical Oncology, 2, 375–379.

DOI Link

Study Purpose

To compare the antiemetic efficacy of second-generation 5HT3 receptor antagonists (RAs) (i.e., palonosetron) with older 5HT3 RAs (i.e., granisetron, azasetron, ramosetron) for controlling acute and delayed chemotherapy-induced nausea and vomiting (CINV) in addition to their effects on patients’ appetites

Intervention Characteristics/Basic Study Process

In this study, 103 patients receiving various chemotherapy regimens with highly emetogenic chemotherapy (HEC) (four regimens) or moderately emetogenic chemotherapy (MEC) (six regimens) were included. One 5HT3 RA (either granisetron, azasetron, ramosetron, or palonosetron) plus dexamethasone and/or aprepitant (a three-drug combination) was administered to 42 patients.

Sample Characteristics

  • N = 103
  • MEDIAN AGE = 61.6 years
  • MALES: 39.8%, FEMALES: 60.2%
  • KEY DISEASE CHARACTERISTICS: Various cancers (most common were colorectal and breast)
  • OTHER KEY SAMPLE CHARACTERISTICS: Receiving HEC (42 patients) or MEC (61 patients); experienced anticipatory CINV 24 hours before chemotherapy administration

Setting

  • SITE: Single site                
  • SETTING TYPE: Inpatient                    
  • LOCATION: Ambulatory therapy center in Japan

Phase of Care and Clinical Applications

  • PHASE OF CARE: Active antitumor treatment

Study Design

Prospective, comparative clinical trial

Measurement Instruments/Methods

  • Patient diaries were completed on days 1–5 using a 100 mm Visual Analog Scale (VAS) to assess CINV severity, the presence of daily vomiting episodes, and the effect of nausea on appetite level on a four-category scale (normal, appetite diminished because of nausea, food portions decreased because of nausea, and almost no food intake because of nausea).
  • The efficacy endpoints were complete response (CR, no emetic episodes and no rescue therapy) and total control (TC, no emetic episodes, no rescue therapy, and no nausea and no appetite loss).

Results

In this study, 42 patients received HEC, and 61 patients received MEC. The CR rates for all patients receiving palonosetron versus a first-generation 5HT3 RA were 86% versus 76%, 93% versus 84%, and 77% versus 72%, respectively. The TC rates for all HEC and MEC patients receiving palonosetron versus ta first-generation 5HT3 RA were 48% versus 43%, 55% versus 52%, and 40% versus 35%, respectively. 
 
In both patients receiving HEC (VAS on day 5) and MEC (VAS on days 3–5), VAS scores were lower in the groups receiving palonosetron than those receiving first-generation 5HT3 RAs. Changes in food intake were assessed in 18 patients for whom granisetron was switched to palonosetron. In the delayed phase, 22.2% of patients (four out of 18) reported increased food intake and exhibited improved appetites.

Conclusions

Palonosetron was more effective in controlling delayed CINV than other conventional 5HT3 RAs (i.e., granisetron). Palonosetron also was safe and was not associated with any severe adverse drug reactions.

Limitations

  • Baseline sample/group differences of import
  • Risk of bias (no control group)
  • Risk of bias (no blinding)
  • Risk of bias (no random assignment) 
  • Risk of bias (no appropriate attentional control condition)
  • Risk of bias(sample characteristics)
  • Unintended interventions or applicable interventions not described that would influence results 
  • Measurement/methods not well described
  • Other limitations/explanation: No stratification of chemotherapy emetogenicity; various chemotherapy regimens; used more than one 5HT3 RA and different forms (i.e., oral, injection) of antiemetics; antiemetic doses and administration frequency not listed

Nursing Implications

Palonosetron was recommended as a 5HT3 RA over older 5HT3 RAs. The efficacy of palonosetron in the delayed phase was confirmed. In this study, patient appetite also improved.