Miura, S., Watanabe, S., Sato, K., Makino, M., Kobayashi, O., Miyao, H., . . . Yoshizawa, H. (2013). The efficacy of triplet antiemetic therapy with 0.75 mg of palonosetron for chemotherapy-induced nausea and vomiting in lung cancer patients receiving highly emetogenic chemotherapy. Supportive Care in Cancer, 21(9), 2575–2581. 

DOI Link

Study Purpose

To evaluate the efficacy of triple antiemetic therapy consisting of a 0.75 mg dose of palonosetron, a three-day course of aprepitant, and four days of dexamethasone in the control of chemotherapy-induced nausea and vomiting (CINV) among chemotherapy-naïve patients with lung cancer undergoing highly emetogenic chemotherapy (HEC) regimens

Intervention Characteristics/Basic Study Process

From September 2010 to June 2012, patients received triplet antiemetic therapy (0.75 mg palonosetron IV + 9.9 mg dexamethasone IV + 125 mg of aprepitant orally) on day 1, followed by 80 mg aprepitant on days 2 and 3, and 8 mg dexamethasone on days 2–4.

Sample Characteristics

  • N = 67 (later excluded 4, N = 63)              
  • MEDIAN AGE: 64 years (range = 36–78 years)
  • MALES: 65.7%, FEMALES: 34.3%
  • KEY DISEASE CHARACTERISTICS: Chemotherapy-naïve patients with lung cancer scheduled to receive HEC [50 mg/m2 or higher dose of cisplatin with concurrent agents (pemetrexed [38.8 %], vinorelbine [32.7 %], gemcitabine [9.0 %], irinotecan [7.5 %], etoposide [7.5 %], and docetaxel [4.5 %])
  • OTHER KEY SAMPLE CHARACTERISTICS: No emesis within 24 hours of chemotherapy administration; no symptomatic or suspected brain metastasis; no concomitant radiotherapy; no complications that prohibited dexamethasone use; and no known hypersensitivity to palonosetron, aprepitant, or dexamethasone

Setting

  • SITE: Multi-site  
  • SETTING TYPE: Outpatient  
  • LOCATION: Japan

Phase of Care and Clinical Applications

  • PHASE OF CARE: Active antitumor treatment

Study Design

Single-arm, phase II prospective, multi-centered, longitudinal trial

Measurement Instruments/Methods

Assessment started at the observation period and lasted for five days. The patients used a daily questionnaire to record any vomiting episodes, nausea ratings, impairment of eating habits, any use of rescue therapy, and the degree of constipation or diarrhea. The patients assessed their nausea with a 100 mm horizontal Visual Analog Scale (VAS). Scores of 5–100 or 25–100 mm on the VAS scale indicated that patients had experienced insignificant or significant nausea, respectively.
 
Study endpoints included:
  • Overall Complete Response (CR) rate: No vomiting, no use of rescue medication
  • CR rate in the acute phase (0–24 hours)
  • CR rate in the late phase (24–120 hours)
  • Complete Control (CC) rate: No vomiting and no significant nausea without needing rescue medication during the acute, delayed, and overall phases
  • The proportion of patients who experienced no nausea, no significant nausea, and no impairment of eating habits during the acute, delayed, and overall phases
  • Safety

 

Results

The CR rates during the acute and delayed phases were 96.8% and 81.0 %, respectively. Almost half of the patients (54.0%) experienced no nausea (VAS < 5 mm) during the overall and delayed phase. The proportion of patients who experienced no significant nausea (VAS < 25 mm) during the overall, acute, and delayed phases was 66.7%, 93.8%, and 66.7%, respectively. 
  • CR rates: 81% (overall), 96.8% (acute), and 81.0% (delayed)
  • CC rates: 63.5% (overall), 92.1% (acute), and 63.5% (delayed)
  • No nausea: 54% (overall), 84.1% (acute), and 54.0% (delayed)
  • No significant nausea: 66.7% (overall), 93.8% (acute), and 66.7% (delayed)
  • More than half of the patients suffered from appetite loss due to CINV.
  • No of adverse events exceeded grade 3 of the Common Terminology Criteria for Adverse Events (CTCAE). Constipation was the most frequent adverse event.

Conclusions

The triplet antiemetic therapy was the most promising regimen in preventing CINV in chemotherapy-naïve patients with lung cancer treated with HEC. The dose-response relationship between palonosetron and aprepitant use needs to be further investigated. However, the experience of nausea by almost half of the patients during the overall phase highlighted the necessity of conducting further investigations to control CINV during the delayed phase.

Limitations

  • Small sample (< 100)
  • Risk of bias (no control group)
  • Risk of bias (no blinding)
  • Risk of bias (no random assignment)
  • Measurement validity/reliability questionable
  • Findings not generalizable
  • No consideration about CINV risk factors such as the explanation not measuring for patients’ history of alcohol consumption; experiencing nausea and vomiting during previous radiotherapy or during pregnancy for female patients; and anxiety level. As the starting of the study was on the first cycle of chemotherapy, the investigators had no chance to determine prior experience of CINV and thus anticipatory nausea and vomiting.

Nursing Implications

Although adding palonosetron to antiemetic regimens shows improvement more impressively in the acute phase among patients, caution should be taken before interpreting the result of this study as it did not use the most robust research design (of randomization, blinding, placebo control) to detect the drug's efficacy. Constipation is a commonly reported adverse effect in this study, therefore careful management should be considered when palonosetron is used.