PHASE-II STUDY WITH CISPLATIN AND PACLITAXEL IN COMBINATION WITH WEEKLY HIGH-DOSE 24 H INFUSIONAL 5-FLUOROURACIL LEUCOVORIN FOR FIRST-LINE TREATMENT OF METASTATIC BREAST-CANCER/

Results from our previous phase II study demonstrating high efficacy a nd low toxicity for a weekly schedule of 5-fluorouracil (5-FU)/leucovo rin in intensively pretreated patients with metastatic breast cancer p rompted addition of paclitaxel and cisplatin to this regimen for a pha se II study of outpatient first-line treatment of metastatic breast ca ncer. (MBC). Twenty-eight patients with metastatic breast cancer have been evaluated. Pretreatment comprised adjuvant CTX in 24 out of 28 pa tients, but no prior CTX for MBC. Patients were treated with 5-FU 2 g/ m(2) (24 h infusion) plus leucovorin 500 mg/m(2) (2 h infusion prior t o 5-FU) weekly for 6 weeks (days 1, 8, 15, 22, 29 and 36); in addition , paclitaxel 175 mg/m(2) (3 h infusion) was administered on days 0 and 21, and cisplatin 50 mg/m(2) (1 h infusion) on days 1 and 22 prior to 5-FU/leucovorin, repeated every 50 days. All patients were treated as outpatients using Port-a-Cath systems and portable pumps. Aside from common total alopecia, neutropenia was common but only of short durati on. No episodes of febrile neutropenia occured. Non-hematologic toxici ties (NCI CTC grade, percent of patients) consisted of mild to moderat e diarrhea (2+3, 47%), mucosits (2, 14%), and nausea and vomiting (2+3 , 60%). Out of 28 patients with bidimensionally measurable disease 25% (seven out of 28) achieved a CR, 57% (16 out of 28) achieved a PR, 11 % (three out of 28) had a SD and 7% (two out of 28) had a PD. Overall RR was 82% (95% confidence interval 66-100%). Median remission duratio n was 8 months, median time to progression 9 months and median survial time 28 months with a median follow-up of 21 months. We conclude that the combination of paclitaxel, cisplatin and 5-FU/leucovorin is an ef fective non-anthracycline-containing regimen for the first-line treatm ent of MBC. [(C) 1998 Rapid Science Ltd.].