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,
In this phase II multicenter trial, trimetrexate plus 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
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.