title: 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.
abstract: Results from our previous phase II study demonstrating high efficacy and low toxicity for a weekly schedule of 5-fluorouracil (5-FU)/leucovorin in intensively pretreated patients with metastatic breast cancer prompted addition of paclitaxel and cisplatin to this regimen for a phase II study of outpatient first-line treatment of metastatic breast cancer. (MBC). Twenty-eight patients with metastatic breast cancer have been evaluated. Pretreatment comprised adjuvant CTX in 24 out of 28 patients, but no prior CTX for MBC. Patients were treated with 5-FU 2 g/m2 (24 h infusion) plus leucovorin 500 mg/m2 (2 h infusion prior to 5-FU) weekly for 6 weeks (days 1, 8, 15, 22, 29 and 36); in addition, paclitaxel 175 mg/m2 (3 h infusion) was administered on days 0 and 21, and cisplatin 50 mg/m2 (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 duration. No episodes of febrile neutropenia occurred. Non-hematologic toxicities (NCl CTC grade, percent of patients) consisted of mild to moderate diarrhea (2+3, 47%), mucositis (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 duration was 8 months, median time to progression 9 months and median survival 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 effective non-anthracycline-containing regimen for the first-line treatment of MBC.
authors.affiliation: Department of Internal Medicine (Cancer Research), West German Cancer Center, University of Essen.
authors.forename: U
authors.initials: U
authors.lastname: Klaassen
authors.forename: H
authors.initials: H
authors.lastname: Wilke
authors.forename: R
authors.initials: R
authors.lastname: Weyhofen
authors.forename: A
authors.initials: A
authors.lastname: Harstrick
authors.forename: W
authors.initials: W
authors.lastname: Eberhardt
authors.forename: C
authors.initials: C
authors.lastname: Müller
authors.forename: M
authors.initials: M
authors.lastname: Korn
authors.forename: M
authors.initials: M
authors.lastname: Hanske
authors.forename: K
authors.initials: K
authors.lastname: Diergarten
authors.forename: S
authors.initials: S
authors.lastname: Seeber
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D017239:Paclitaxel; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil