Nakatsumi, H., Komatsu, Y., Yuki, S., Sogabe, S., Tateyama, M., Muto, S., ... Asaka, M. (2012). Optimal dose period for indisetron tablets for preventing chemotherapy-induced nausea and vomiting with modified FOLFOX6: A randomized pilot study. Chemotherapy, 58(6), 439–444. 

To determine the optimal dosing period for indisetron during modified FOLFOX6 in patients with advanced colorectal cancer

Eligible patients were randomly assigned to receive either a three-day or one-day endisetron dosing regimen arm. On day 1, indisetron 8 mg was administered orally and dexamethasone 8 mg was administered intravenously 30 to 120 minutes prior to the administration of oxaliplatin. In the three-day regimen arm, indisetron 8 mg was administered orally in the morning of days 2 and 3. In the one-day regimen, no prophylactic medications were given on days 2 and 3. Rescue medication was permitted, including dexamethasone and/or metoclopramide for the treatment of breakthrough emesis on an as-needed basis. The follow-up period was five days from the start of chemotherapy. The primary endpoint was complete protection from vomiting, defined as no vomiting for five days after initiation of chemotherapy.

• N = 42 
• MEDIAN AGE: 60 years (three-day group); 67 years (one-day group); range = 37–80 years
• MALES: 57 %, FEMALES: 43%
• KEY DISEASE CHARACTERISTICS: Chemotherapy-naive patients with advanced colorectal cancer receiving modified FOLFOX6 without administration of molecular-targeted agents.
• OTHER KEY SAMPLE CHARACTERISTICS: Other eligibility criteria include age between 20 and 80 years; a score of 0–2 on the Eastern Cooperative Oncology Group performance status; and adequate hematologic, hepatic, and renal function.

• SITE: Multi-site  
• SETTING TYPE: Not specified  
• LOCATION: Patients were all treated at eight hospitals belonging to the Hokkaido Gastrointestinal Cancer Study Group in Japan.

• PHASE OF CARE: Active antitumor treatment

Multi-center, randomized, comparative, open-label pilot study

• Common Terminology Criteria for Adverse Events version 3.0

The proportion of patients with complete protection from vomiting was 85.7 % (95% CI 63.7–97.0) in the three-day regimen arm and 81% (95% CI 58.1–94.6) in the one-day regimen arm. In the acute phase, the proportion of patients with no nausea was 100% in the three-day arm and 95.2% in the one-day arm. The proportion of patients with complete response in the delayed phase was 66.7% in the three-day regimen arm and 57.1% in the one-day regimen arm. No-rescue therapy rates were 66.7% (95% CI 43.0–85.4) in the three-day regimen and 57.1% (95%CI 34.0–78.2%) in the one-day regimen. Severity of nausea and vomiting based on the worst grade was similar between both regimens.

The study demonstrated that three-day dosing of indisetron is equivalent in efficacy to a one-day dosing schedule for patients receiving mFOLFOX6. The combination of indisetron and dexamethasone is effective in preventing emesis in about 80% of patients receiving mFOLFOX6. However, neither regimen (three-day or one-day) was particularly effective for preventing delayed chemotherapy-induced nausea and vomiting (CINV).

• Small sample (< 100)
• Risk of bias (no control group)
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Findings not generalizable

This study demonstrated equivalent efficacy for indisetron plus dexamethasone with past 5-HT3 receptor antagonists to prevent acute CINV with mFOLFOX6. However, multiday dosing was not effective in preventing delayed CINV in many patients. This article does not provide evidence to support a practice change.