Hecht, J.R., Pillai, M., Gollard, R., Heim, W., Swan, F., Patel, R., . . . Malik, I. (2010). A randomized, placebo-controlled phase ii study evaluating the reduction of neutropenia and febrile neutropenia in patients with colorectal cancer receiving pegfilgrastim with every-2-week chemotherapy. Clinical Colorectal Cancer, 9, 95–101.

The purpose of this study is to evaluate whether prophylactic pegfilgrastim administered with first- or second-line chemotherapy was feasible and reduced the incidence of grade 3/4 neutropenia and neutropenia-related complications in patients receiving 14-day oxaliplatin- or irinotecan-containing 5-FU–based chemotherapy regimens for advanced or metastatic colorectal cancer (CRC). 

One of three chemotherapy regimens (FOLFOX 4, FOLFIRI, or FOIL) was selected by physician discretion. Patients were randomized to receive either pegfilgrastim 6 mg or placebo on day 4 of each 14-day regimen. During the study period (the first four cycles of chemotherapy), the incidence of grade 3/4 neutropenia and febrile neutropenia were compared between the pegfilgrastim and placebo groups.

• The sample size was 241 at baseline; 135 completed the study.  
• All were adults aged 18 years or older.
• Men made up 67% of the sample; women made up 33%.
• A key disease characteristic was locally advanced or metastatic CRC not curable by surgery and not amenable to curative radiation therapy

• Multi-site (54 sites) 
• Outpatient settings  
• United States
   

Active treatment

Randomized, controlled trial, double-blinded. The control group received placebo.

• Laboratory results (complete blood count with five-part differential)    
• Patient temperatures, either reported or taken by healthcare provider
• Adverse events (nausea, diarrhea, fatigue, anemia, vomiting, anorexia, dehydration, abdominal pain, asthenia, pyrexia, decreased weight, hypokalemia, insomnia, neutropenia, constipation, alopecia, bone pain, dyspnea, pain, and febrile neutropenia)
   

Patients treated with pegfilgrastim were significantly less likely (13%) to develop grade 3/4 neutropenia than those who received a placebo (43%) (p < 0.05). The pegfilgrastim group also experienced significantly fewer dose delays or dose reductions (33.4% versus 45%) (p < 0.05).

The study compares pegfilgrastim versus placebo, but does not consider pegfilgrastim versus filgrastim, which may have similar efficacy at reduced expense. Additional study is warranted, including a cost-benefit analysis.

•  The study authors disclosed potential conflicts of interest, including owning stock in Amgen, the company that produces pegfilgrastim.
•  Amgen also provided writing assistance for this article, which raises questions of bias.

Patients with CRC receiving every-two-week chemotherapy regimens may benefit from supportive medications to stimulate neutrophil production.