Segawa, Y., Aogi, K., Inoue, K., Sano, M., Sekine, I., Tokuda, Y., … Atagi, S. (2009). A phase II dose-ranging study of palonosetron in Japanese patients receiving moderately emetogenic chemotherapy, including anthracycline and cyclophosphamide-based chemotherapy. Annals of Oncology, 20, 1874–1880. 

To identify the most effective dose of palonosetron when combined with fixed doses of dexamethasone in patients receiving chemotherapy of emetogenicity level 3 or 4 on the National Comprehensive Cancer Network (NCCN) 2004 guidelines

Patients were randomly assigned to receive a single IV dose of palonosetron of 0.075, 0.25 or 0.75 mg over 30 seconds administered 30 minutes before the first dose of chemotherapy on day one. Daily episodes of vomiting, severity of nausea, and patient satisfaction were recorded daily in patient diaries. Care providers recorded the use of rescue medications. All patients received 8 mg IV dexamethasone 45 minutes prior to the palonosetron. Patients had to be hospitalized for the first two days. Follow-up assessment was done on days 6–10 and days 14–20.

• The study consisted of 204 participants.
• The average age 61.4 years.
• The majority of participants were female (56.9%).
• The most common cancer types were non-small cell lung cancer (NSCLC), breast cancer, and small cell lung cancer.
• The most common chemotherapeutic agents used on day one were carboplatin, paclitaxel, cyclophosphamide, epirubicin, and doxorubicin.
• All patients had Eastern Cooperative Oncology Group (ECOG) performance statuses of 1 or 2.

The study was conducted at multisite, inpatient settings in Japan.

All patients were in active treatment.

This was a randomized, double-blind trial.

• Patient diaries were used to record nausea severity via a Likert-type scale.
• Complete response (CR) was defined as no emetic episodes and no use of rescue medication in the first 24 hours.

• CR rates in the acute phase were 85.1%, 82.4%, and 92.8%, respectively for the 0.075-, 0.25-, and 0.75-mg palonosetron dose groups.
• No significant dose response was found.
• For nausea in the delayed phase, no clinically relevant dose response was found and CR rates for delayed nausea ranged from 62.7%–71%.
• The most commonly reported events were headache and constipation. Neither prevalence nor severity appeared to be palonosetron-dose related.
• In patients who received a combination of anthracyclines and cyclophosphamide, the CR rates for delayed and overall phases of care appeared to be somewhat dose related.

Palonosetron in single doses from 0.075 to 0.75 mg appeared to be well tolerated. Optimal dosages for prevention and management of chemotherapy-induced nausea and vomiting (CINV) in these patients remain unclear.

• The authors concluded that higher palonosetron doses are indicated; however, the study results did not support this conclusion.
• Either a single emesis or what could amount to intractable emesis appears to have counted as a single episode. This approach, while useful for the purpose of analysis, does not seem realistic and appropriate.
• The method of rating severity of nausea was not well described.
• Patient compliance with diary recordings and missing data were not discussed.

The optimal dosage of palonosetron in patients who are receiving moderately emetogenic chemotherapy (MEC) remains unclear. A range of doses appears to be well tolerated.