Oral Regimen of UFT/Leucovorin and Etoposide Shows Promising Results

PALO ALTO, California—Treatment with oral chemotherapy for metastatic breast cancer showed promising efficacy with minimal toxicity and warrants further investigation, according to results of a phase I trial conducted at Stanford University. Anne-Renee Hartman, MD, reported the findings at an ASCO poster session (abstract 235). "I wanted to develop an oral chemotherapy regimen for women with metastatic disease," she said. "The current intravenous treatments have a lot of toxicity. Since there is no cure for metastatic disease, the goal should be to keep the disease in check or decrease the amount of disease using the mildest chemotherapy possible."

Determined to improve patients’ quality of life with a convenient, well-tolerated, and efficacious treatment, the investigators designed an oral chemotherapy regimen consisting of 28-day cycles of etoposide (VePesid) and uracil/tegafur (UFT) plus leucovorin (UFT/LV, also known as Orzel, investigational). Leucovorin is used because it potentiates UFT’s antitumor effect.

On days 1 to 14, 21 patients received etoposide 50 mg/m² and escalating doses of UFT, starting at 200 mg/m² and increasing in 50 mg/m² increments up to 350 mg/m². All patients received leucovorin, 30 mg thrice daily. The investigators believe 250 mg/m² of UFT to be the optimal dose, but they have not completed the final analysis.

All patients were required to have received prior treatment with a taxane or an anthracyline. "Ethically, it was important that they had the first-line treatment before starting the trial," Dr. Hartman explained. "This group was heavily pretreated."

Six patients had two prior chemotherapy regimens for metastatic disease, six had three prior rounds, five had four prior treatments, and three had received five or more regimens. Two patients had prior adjuvant treatment with doxorubicin and paclitaxel (Taxol) with immediate progression.

"Whenever one regimen stops working, you put them on another," Dr. Hartman said. "Patients with more prior chemotherapy are less likely to respond to something new."

But the patients did respond to the Stanford researchers’ regimen. Half of the 20 patients experienced a partial response, and 12.5% stable disease. Median progression-free survival was 11 months. "The response rate was good enough to warrant phase III trials," Dr. Hartman said. "This regimen should be compared to standard first-line therapy for metastatic disease."

In addition to the favorable response rate, the regimen required minimal time in the clinic. After the first two doses, the patients returned monthly, so investigators could monitor toxicities and refill the chemotherapy prescription. One patient has been on the trial for 19 months.

Patients experienced no grade 3-4 nonhematologic toxicities. In those receiving 250 mg/m², one patient had grade 4 neutropenia lasting more than a week, considered a dose-limiting toxicity. At 300 mg/m², hematologic toxicities included one patient with dose-limiting toxicity (platelet count less than 50,000/mm³).

"I think the quality of life is really good for patients on the trial," Dr. Hartman concluded.