Our phase II study results demonstrating high efficacy and low toxicity for a weekly schedule of high-dose, 24-hour infusional
5-fluorouracil(5-FU)/
folinic acid (HD5-FU/FA) in intensively pretreated patients with metastatic
breast cancer prompted addition of
paclitaxel (
Taxol) to the regimen, for a phase I/II study of outpatient second-line treatment of metastatic
breast cancer. That study further prompted the addition of
cisplatin (
Platinol) to the regimen for first-line treatment. So far, 28 patients with metastatic
breast cancer have been evaluated. Pretreatment comprised
adjuvant chemotherapy in 24 of 28 patients, but no prior
chemotherapy for metastatic disease. Patients were treated with HD5-FU 2 g/m2 (24-hour infusion) plus FA 500 mg/m2 (2-hour infusion prior to FU) weekly for 6 weeks (days 1, 8, 15, 22, 29, and 36); in addition,
paclitaxel 175 mg/m2 (3-hour infusion) was administered on days 0 and 21 and
cisplatin 50 mg/m2 (1-hour infusion) on days 1 and 22 prior to HD5-FU/FA, repeated every 50 days. Patients were treated as outpatients using
Port-a-Cath systems and portable pumps.
Neutropenia was common (67% World Health Organization grade 3) but mild to moderate in most patients and was of short duration. No hospitalizations were required because of
febrile neutropenia, and no
granulocyte colony-stimulating factor support was used. Aside from common total
alopecia, nonhematologic toxicities consisted mainly of moderate
myalgia,
diarrhea,
mucositis, and
nausea and
vomiting.
Hand-foot syndrome and
peripheral neuropathy were cumulative and occurred most commonly during the third treatment cycle, with mild-to-moderate expression. In 28 patients with bidimensionally measurable disease, 25% (7/28) attained a complete response, 57% (16/28) achieved partial response, 11% (3/28) had stable disease, and 7% (2/28) had
disease progression. Overall response was 82% (95% confidence interval, 66% to 100%). Eight of 28 patients are still receiving treatment. It is concluded that the combination of
paclitaxel/cisplatin with weekly HD5-FU/FA appears to be effective in the first-line treatment of metastatic
breast cancer. Preliminary results must be confirmed by the final analysis of response duration, time to progression, and survival.