PALO ALTO, CaliforniaTreatment 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
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
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