Trimetrexate Appears Beneficial in Colorectal Cancer

July 1, 1996

PHILADELPHIA--The addition of trimetrexate (NeuTrexin) to the standard chemotherapeutic regimen of fluorouracil and leucovorin in patients with metastatic colorectal cancer resulted in an improved response rate with no greater toxicity in a study reported at the Oncology Nursing Society meeting.

Nurses administering this treatment should monitor patients carefully,assess quality of life factors, and take a proactive approachto managing any side effects, said Janet Cogswell, RN, and ShirleyHwang, RN, of the Veterans Affairs Medical Center, East Orange,NJ.

In this phase II multicenter trial, trimetrexate plus fluorouracil/leucovorinproduced an overall response rate of 48%. The findings confirmearlier trials of colorectal patients, both previously treatedand untreated, that achieved overall response rates ranging from20% to 53%.

In the study, 36 patients were treated on an 8-week cycle (6 weekson, 2 weeks off). On day 1, a 110 mg/m² IV infusion of trimetrexatewas given over 60 minutes; on day 2, leucovorin (200 mg/m²IV infusion) was given over 60 minutes, immediately followed byfluorouracil (500 mg/m² IV bolus). On days 2 and 3, sevendoses of oral leucovorin (15 mg) were given every 6 hours, starting6 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 teamapproach to toxicity management are critical.

"Nurses play a major role in education," Ms. Cogswellsaid. "It's important to teach patients up front about possibletoxicities 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 loperamideat the first loose bowel movement, and those who have more thansix or eight loose bowel movements in a day should be hospitalizedimmediately and treated for dehydration, the researchers advised.

A few histamine (possibly allergic) reactions, characterized byrigors, occurred, although not until patients had returned home,"so it's very important that they be encouraged to tell thetreatment team what side effects, if any, they are having aftertreatment and be taught how to handle them," Ms. Cogswellsaid. Di-phenhydramine, she said, is effective in controllingthe histamine reaction.

The study also assessed patients' quality of life every 4 weeks,using Symptom Distress Scale data. Physical, emotional, socialand functional issues were examined, as well as the quality ofpatients' relationships with their physician.

"Quality of life is multidimensional, based on the patient'sown perceptions and no one else's," Ms. Hwang stressed. "Inthis study, patients reported an increased appetite and improvedperformance status, benefits that appear to be due to the additionof trimetrexate."

Trimetrexate (with concurrent leuco-vorin) is commercially availableas an alternative to trimethoprim-sulfameth-oxazole for the treatmentof Pneumocystis carinii pneumonia. The agent was developedto address problems with classical antifolates such as methotrexate,the researchers said. It has a wider spectrum of activity thanmethotrexate and is active against cancers that have acquiredresistance to the parent drug.

A double-blind, multicenter phase III trial comparing trimetrexate/fluorouracil/leucovorinwith the standard regimen is underway, with preliminary resultsexpected in about a year, the investigators said. The EORTC hasinitiated a similar trial in Europe.