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)/
leucovorin (LV) in intensively pretreated patients with metastatic
breast cancer prompted the addition of
paclitaxel (
Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 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 to the regimen for first-line treatment. Twenty-eight 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 high-dose
5-FU 2 g/m2 (24-hour infusion) plus LV 500 mg/m2 (2-hour infusion before 5-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 before high-dose 5-FU/LV, repeated every 50 days. Patients were treated as outpatients using
Port-a-Cath systems (SIMS Deltec Inc, St Paul, MN) and portable pumps.
Neutropenia was common but mild to moderate and of short duration in most patients. 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% (seven of 28) attained a complete response, 57% (16 of 28) achieved a partial response, 11% (three of 28) had stable disease, and 7% (two of 28) had
disease progression. Overall response was 82% (95% confidence interval, 66% to 100%). We conclude that the combination of
paclitaxel/cisplatin with weekly high-dose infusional 5-FU/LV 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.