Schwartzberg, L., Barbour, S.Y., Morrow, G.R., Ballinari, G., Thorn, M.D., & Cox, D. (2013). Pooled analysis of phase III clinical studies of palonosetron versus ondansetron, dolasetron, and granisetron in the prevention of chemotherapy-induced nausea and vomiting (CINV). Supportive Care in Cancer, 22(2), 469–477. 

DOI Link

Study Purpose

To determine the safety and efficacy of palonosetron versus older 5-HT3 receptor antagonists in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving ​moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC)

Intervention Characteristics/Basic Study Process

Data were pooled from four multi-center, randomized, double-blind, parallel-group phase III trials. Patients enrolled in the four studies received either MEC or HEC. Patients were assigned to receive a single dose 30 minutes prior to chemotherapy of IV palonosetron (0.25 mg or 0.75 mg) or an older 5-HT3 such as ondansetron (32 mg), dolasetron (100 mg), or granisetron (40 µg/kg). Guidelines at the time of each study for steroids were followed. 
  • Acute phase = 0–24 hours after chemotherapy administration
  • Delayed phase = > 24–120 hours after chemotherapy administration
  • Overall phase = 0–120 hours after chemotherapy administration

Sample Characteristics

  • N = 2,962  
  • MEAN AGE = 55 years
  • MALES: 36%, FEMALES: 64%
  • KEY DISEASE CHARACTERISTICS: All types of cancer

Setting

  • SITE: Multi-site    
  • SETTING TYPE: Outpatient    
  • LOCATION: United States and Japan

Phase of Care and Clinical Applications

  • PHASE OF CARE: Active antitumor treatment

Study Design

  • Secondary analysis

Measurement Instruments/Methods

  • Complete response (CR): No emesis and no rescue medication in acute or delayed phase
  • Complete control (CC): No emesis, no rescue medications, and no more than mild nausea during all phases
  • Number of emetic episodes
  • Number of nausea episodes
  • Likert scale to measure nausea
  • Adverse events, vital signs, laboratory tests, and ECG findings

Results

CR rates were significantly higher for patients who received palonosetron during the delayed (p < 0.0001) and overall (p < 0.0001) phases. There was a greater likelihood for patients who received palonosetron to achieve a CR in the delayed (OR, 1.62 [1.40–1.88]) and overall (OR, 1.56 [1.34–1.81]) phases. CC rates were significantly higher in patients who received palonosetron in the delayed (p < 0.0001) and overall (p < 0.001) phases. No differences in CR or CC were seen between groups in the acute phase. There was a significant difference in the number of emetic episodes in patients who received palonosetron in the acute (p = 0.007), delayed (p < 0.0001), and overall (p < 0.0001) phases. Significant differences were seen in the severity of nausea in the delayed (p = 0.0002) and overall (p = 0.011) phases.

Conclusions

Palonosetron is more effective at achieving CR and CC for CINV in the delayed and overall phases when compared to older 5-HT3 receptor antagonists. Palonosetron is also more effective at reducing the severity of nausea experienced in the delayed and overall phases after chemotherapy. However, in the acute phase, palonosetron is not more effective at controlling CINV compared to older 5-HT3 receptor antagonists.

Limitations

  • Baseline sample/group differences of import
  • Other limitations/explanation: Patients in Japanese study had lower body weights. The majority patients who received HEC were given steroids but some were not; some patients who received MEC received steroids but some did not.

Nursing Implications

For patients receiving MEC or HEC, the use of palonosetron rather than an older 5-HT3 receptor antagonist is more effective at controlling CINV in the delayed and overall phase after chemotherapy.