Nurses administering this treatment should monitor patients carefully, assess quality of life factors, and take a proactive approach to managing any side effects, said Janet Cogswell, RN, and Shirley Hwang, RN, of the Veterans Affairs Medical Center, East Orange, NJ.
In this phase II multicenter trial, trimetrexate(Drug information on trimetrexate) plus fluorouracil(Drug information on fluorouracil)/leucovorin produced an overall response rate of 48%. The findings confirm earlier trials of colorectal patients, both previously treated and untreated, that achieved overall response rates ranging from 20% to 53%.
In the study, 36 patients were treated on an 8-week cycle (6 weeks on, 2 weeks off). On day 1, a 110 mg/m² IV infusion of trimetrexate was given over 60 minutes; on day 2, leucovorin (200 mg/m² IV infusion) was given over 60 minutes, immediately followed by fluorouracil (500 mg/m² IV bolus). On days 2 and 3, seven doses of oral leucovorin (15 mg) were given every 6 hours, starting 6 hours after the fluorouracil bolus.
Toxicities were comparable to those in the standard two-drug regimen, Ms. Cogswell said, but, she added, patient education and a team approach to toxicity management are critical.
"Nurses play a major role in education," Ms. Cogswell said. "It's important to teach patients up front about possible toxicities and how to manage them at home, such as taking Compazine [pro-chlorperazine] for nausea/vomiting."
The most common side effect in the trimetrexate regimen was diarrhea (60% of patients). Patients should be instructed to take loperamide(Drug information on loperamide) at the first loose bowel movement, and those who have more than six or eight loose bowel movements in a day should be hospitalized immediately and treated for dehydration, the researchers advised.
A few histamine (possibly allergic) reactions, characterized by rigors, occurred, although not until patients had returned home, "so it's very important that they be encouraged to tell the treatment team what side effects, if any, they are having after treatment and be taught how to handle them," Ms. Cogswell said. Di-phenhydramine, she said, is effective in controlling the histamine reaction.