Ikari, Y., Ogata, K., Nakashima, Y., Sato, E., Masaki, M., Katsuya, H., . . . Tamura, K. (2014). Safety and pharmacokinetic evaluation of repeated intravenous administration of palonosetron 0.75 mg in patients receiving highly or moderately emetogenic chemotherapy. Supportive Care in Cancer, 22, 1959–1964.

DOI Link

Study Purpose

To evaluate the safety, efficacy, and pharmacokinetics of repeated doses of palonosetron 0.75 mg on days 1 and 3 in Japanese patients who received highly emetogenic chemotherapy (HEC)

Intervention Characteristics/Basic Study Process

On day 1, patients received 0.75 mg of IV palonosetron and 12–16 mg of dexamethasone 30 minutes before chemotherapy. On day 2, patients received 4–8 mg of dexamethasone. On day 3, patients received a booster of 0.75 mg IV bolus palonosetron and 4–8 mg of dexamethasone.  
 
The primary endpoints were safety and pharmacokinetics in a subset of six patients (from 24 hours before palonosetron administration till eight days after administration). Blood samples were taken at 15 and 30 minutes and at one, four, eight, and 24 hours after the first dose on day one. On day 3, samples were taken before the dose of palonosetron and at 15 and 30 minutes and at one, four, eight, 24, and 48 hours after the second dose. Secondary endpoints were complete response and complete protection (from 0–192 hours).

Sample Characteristics

  • N = 26 (six patients enrolled in the pharmacokinetic [PK] arm)
  • MEDIAN AGE = 59 years
  • MALES: 38.5% (PK 50%), FEMALES: 50% (PK 50%)
  • KEY DISEASE CHARACTERISTICS: Various cancers (73.1% hematologic)
  • OTHER KEY SAMPLE CHARACTERISTICS: Adults aged greater than 20 years receiving HEC or moderately ​emetogenic chemotherapy (MEC); adequate hepatic, renal, and bone marrow function with no corrected electrocardiogram QT intervals > 450 ms; not sensitive to palonosetron or dexamethasone

Setting

  • SITE: Single site
  • SETTING TYPE: Inpatient
  • LOCATION: Fukuoka, Japan

Phase of Care and Clinical Applications

  • PHASE OF CARE: Active antitumor treatment

Study Design

Prospective pharmacologic safety and efficacy clinical trial

Measurement Instruments/Methods

  • Safety was evaluated on the basis of the blood test results, blood chemical analyses, and electrocardiography. Signs and symptoms were graded according to the Common Terminology Criteria for Adverse Events (CTCAE).
  • Complete response (CR) was defined as no emetic episodes and no use of rescue medication. No emetic episodes, no use of rescue medication, and no significant nausea was defined as complete protection (CP). Efficacy was evaluated on the basis of patient diaries.

Results

The pharmacokinetic results are not included here as they were specific to pharmacists. The main treatment-related adverse effects were constipation (77%), diarrhea (15.4%), and pain (7.7%). CR was achieved by 96.2% of patients in the acute phase. In the delayed phase, the CR rate was 76.9 %, and the CP rate was 61.5%. The percentage of patients without nausea in the acute phase was 80.8% and 53.8% in the delayed phase.

Conclusions

Repeated treatment with palonosetron was safe and well tolerated by patients who received HEC or MEC.

Limitations

  • Small sample (< 30)
  • 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)  
  • Measurement validity/reliability questionable
  • Other limitations/explanation: Not controlled for aprepitant use; used a diary to report delayed nausea and vomiting

Nursing Implications

In this study, patients with cancer receiving HEC or MEC often experienced delayed nausea despite booster doses of palonosetron 0.75 mg IV on day 3. One of the common adverse effects of this drug was constipation.